‘Chemical imbalance’

There’s a lot of chat around at the moment about ‘chemical imbalance’… and I’ve written a lot over the years about it and here’s a link to the collected articles.

The term Selective Serotonin Reuptake Inhibitor (SSRI) was invented by a marketing company to sell Seroxat/Paxil to the public. Along with this serious medical sounding piece of jargon, came the fairy tale of the ‘chemical imbalance’

When I started taking Seroxat in 1997, I wanted to know how this great new drug worked – the PIL (the leaflet that came with the tablets) told me “it boosts the levels of serotonin in your brain and that’s what makes you stop feeling depressed”. It’s a simple chemical imbalance said the PIL.

In 2003, GSK said in it “Seroxat is one of a group of medicines called selective serotonin reuptake inhibitors (SSRIs) and works by bringing the levels of serotonin back to normal.”

All lies. The chemical imbalance ‘theory’ HAS NEVER BEEN PROVED.

• I have challenged Glaxo many times before through these pages to tell me exactly how Seroxat actually works. They can’t tell me.

• I have asked what the ‘normal’ brain level of Serotonin is – is it 5? Is it 50? Is it 500? It can’t be measured.

• I have asked them how brain levels of Serotonin can be measured in living humans. It can’t be measured.

Maybe the Royal College of Psychiatrists and their hashtag – #ADsMythBuster – can answer the three simple questions above – but somehow I doubt they will be able to…

 

The Chemical imbalance ‘theory’… come on Glaxo – PROVE it now

When I started taking Seroxat in 1997, I wanted to know how this great new drug worked – the PIL (the leaflet that came with the tablets told me)“it boosts the levels of serotonin in your brain and that’s what makes you stop feeling depressed” I was told. It’s a simple chemical imbalance said the PIL.

By 2003, GSK said in it “Seroxat is one of a group of medicines called selective serotonin reuptake inhibitors (SSRIs) and works by bringing the levels of serotonin back to normal.”

All lies.

The chemical imbalance ‘theory’ HAS NEVER BEEN PROVED. NEVER.

Finally by mid 2006 GSK was starting to get closer to admitting the truth in its PIL “It is not fully understood how Seroxat and other SSRIs work…” At least that’s what they tell us in the UK and USA… however today in Australia, Aropax (the Aussie name for Seroxat/Paxil) still works as it “corrects the chemical imbalance and so helps relieve the symptoms of depression.”

Now read on:

“The Media and the Chemical Imbalance Theory of Depression” by Jonathan Leo & Jeffrey R. Lacasse is a follow up to their seminal article in PLoS Medicine (2005), in which they debunked the “chemical imbalance” theory of depression.

The “chemical imbalance” theory in psychiatry rests on the observation that mood could be artificially manipulated with drugs-those which raised monoamine levels improved mood, while those which lowered amine levels led to depression, but it remained to be seen if naturally occurring fluctuations in neurotransmitter levels were responsible for, or caused, the ebb and flow of mood levels. As the authors point out, in spite of the enormous amount of money and time that has been spent in the quest to confirm the chemical imbalance theory, direct proof has never materialized. Moreover, during the past several decades, a significant amount of evidence has accumulated which calls the theory’s validity into question.

Of particular note, in the two years since publication of their PLoS article, not a single scientific article challenged their conclusion. Indeed, the chairman of FDA Psychopharmacology Advisory Committee acknowledged that the “chemical imbalance” theory was but a “useful metaphor”–as opposed to a valid hypothesis.

Another credible, evidence-based assessment of the “chemical imbalance” theory is to be found on the website of The Mental Health Service at McGill University: “The term ‘chemical imbalance’ is thrown around a lot these days. True conditions caused by chemical imbalances are relatively rare. All thoughts, feelings and motions in the brain are mediated by the release of chemicals in brain pathways. Every person’s brain is unique, leading each of us to have different traits and abilities. Just because your brain works in a particular way does not mean that you have a chemical imbalance. A certain amount of sadness, anxiety or other emotional upset is normal, and though we may be able to block these feelings by chemicals, this would tend to dehumanize us. Even when we use medication to help an individual with overwhelming emotions, most of the time this is not to repair a ‘chemical imbalance’ but simply to help contain symptoms.” (Link here)

However, invalid thought it may be, as Drs. Leo and Lacasse point out the “chemical imbalance” theory has had extraordinary commercial value for both the pharmaceutical industry and psychiatry: “With the advent of the chemical imbalance theory, the companies were no longer just providing soothing tonics, they were now providing medications to treat diseases, as exemplified by an early SSRI advertisement stating: “When serotonin is in short supply, you may suffer from depression.” The wording here is all-important. The advertisement takes a correlation between serotonin shortage and psychological stress-and even this is highly questionable and unverifiable in any individual case-and makes a leap of faith to the conclusion that depression is caused by a serotonin imbalance, not that psychological stress impacts the serotonin system. And the marketing did not stop with depression; eventually we were told that whatever our problems might be, whether anxiety, excessive shyness, depression, or the inability to pay attention, the underlying cause was a faulty transmitter level which could be rectified with a pill. A 2005 survey from the Harvard School of Public Health reported that nearly half of all Americans will at some point develop a mental illness, presumably from a chemical imbalance, with 29% developing an anxiety disorder and 20% a mood disorder.”

The “chemical imbalance” theory has provided promoters of psychoactive “feel good” prescription drugs with the means for distancing their products from illicit street drugs whose chemical action is almost indistinguishable. Whereas drugs used to “take the edge off” stress are typically considered street drugs and are consumed by “users” or “addicts,” substances used to rectify a “chemical imbalance” can be called medications–and these are legitimately consumed by patients.

A fly in the ointment occurred when Ricky Williams, the star running back for the Miami Dolphins who had been “diagnosed” with Social Anxiety Disorder, and for several years was paid by GlaxoSmithKline to promote Paxil for anxiety disorder, was described in 2002, by People magazine, as suffering from a “depression-like chemical imbalance that affects roughly three million Americans.” Williams tested positive for marijuana on several occasions. But while his marijuana use was frowned upon, his use of Paxil was considered acceptable. One was a medication supposed to treat a chemical imbalance, while the other was a drug signaling a lack of willpower.

However, Williams’ contract with Glaxo came to a sudden halt in 2004, when he stated that marijuana was ten times better than Paxil. What got him into hot water, Drs. Leo and Lacasse, note, was not so much praising the competition, but rather putting his sponsor’s “medication” in the same category as an illicit drug. Williams threatened the assumption underlying the conventional unsupportable divide between legal and illegal drug use. His juxtaposition threatened the most powerful industries–including professional sports, the pharmaceutical industry, psychiatry, and the mass media.

Another fly in the ointment raising questions about the validity of the dividing line between prescribed and illicit psychoactive substances, is a recent controlled clinical trial conducted by researchers at Johns Hopkins. The researchers ostensibly tested the “Mystical” effects of psilocybin, the active ingredient in mushrooms which is an illegal drug that causes hallucinations. However, two months after the trial they found that “79% of those prescribed psilocybin reported moderately or greatly increased levels of life satisfaction compared with those given a placebo. A majority said their mood, attitudes and behaviors had changed for the better.” [Link] No SSRI clinical trial had that high a rate of long-lasting improvements in mood, attitude and behavior.

The authors sent inquiries to reporters who mentioned the “chemical imbalance” theory as if it had been proven, asking for citations of such proof. The responses–or lack of responses–and the biased, pro-industry reporting about mental health treatments, are no less troubling than the biased reporting in the New York Times about the events leading up to the Iraq War.

“In hindsight, as the Times editors now acknowledge (5/326/04), Judith Miller’s war coverage was overly one-sided. Her fundamental flaw could be described as a lack of professional skepticism toward the Bush administration, as she willingly parroted what those pushing for war were saying, while giving little credence to the stance of the other side. Writing in the New York Review of Books, Michael Massing commented that the Times and Miller’s reporting were examples of media “submissiveness.”

This depiction could just as well apply to the media’s reporting of mental health issues. As just one example, in some cases, the media still go to the people responsible for the original problems. For instance, several of the researchers involved with the studies of SSRIs in children are still cited in the press even though the following information has come out about their published studies: they downplayed the suicide risk; they exaggerated the benefits; and the papers published under their names were actually written by ghostwriters paid by the pharmaceutical industry.

The Times editors have acknowledged both the problems with Miller’s reporting and their own lack of editorial oversight of her. It remains to be seen if members of the media will ever look inward and reflect on their role in the promotion of the chemical imbalance theory. (For those familiar with the New York Times’ coverage of mental health issues over the past 10 years, it is refreshing that after a series of health reporters who essentially abdicated their role as investigative journalists, there is a newer group of Times reporters with more skeptical inclination…

Thanks to the AHRP blog for this.

Both articles by Jonathan Leo and Jeffrey Lacasse are freely accessible. The first is here and the latest paper can be found here.

I’ve written on this issue before – to catch up please have a look here and here.

And remember this – the chemical imbalance ‘theory’ HAS NEVER BEEN PROVED. NEVER.

All it is, is a marketing idea – a sales tool.

The myth of the chemical cure and the lie of serotonin imbalance

I’ve written about the myth of the chemical cure and the lie of serotonin imbalance before:

Is Clinical Depression Caused by a Serotonin Imbalance?

The Chemical imbalance ‘theory’… come on Glaxo – PROVE it now

Jury Trials In 2008 Expected To Expose SSRI Maker’s Dirty Secrets

Everything you ever wanted to know about… Serotonin

The term Selective Serotonin Reuptake Inhibitor (SSRI) was invented by a marketing company to sell Seroxat/Paxil to the public. Along with this serious medical sounding piece of jargon, came the fairy tale of the ‘chemical imbalance’

When I started taking Seroxat in 1997, I wanted to know how this great new drug worked – the PIL (the leaflet that came with the tablets) told me “it boosts the levels of serotonin in your brain and that’s what makes you stop feeling depressed”. It’s a simple chemical imbalance said the PIL.

In 2003, GSK said in it “Seroxat is one of a group of medicines called selective serotonin reuptake inhibitors (SSRIs) and works by bringing the levels of serotonin back to normal.”

All lies.

The chemical imbalance ‘theory’ HAS NEVER BEEN PROVED.

NEVER.

Finally by mid 2006 GSK was starting to get closer to admitting the truth in its PIL “It is not fully understood how Seroxat and other SSRIs work…”

If you take an SSRI or SNRI ask to your doctor what the correct level of brain serotonin is – then ask them to measure your current level of brain serotonin… they won’t be able to tell you and they won’t be able to measure it – chemical imbalance is a myth created by drug companies to market their product

Now (July 2009) this from the BBC:

Taking a pill to treat depression is widely believed to work by reversing a chemical imbalance.

But in this week’s Scrubbing Up health column, Dr Joanna Moncrieff, of the department of mental health sciences at University College London, says they actually put people into “drug-induced states”.

If you’ve seen a doctor about emotional problems some time over the past 20 years, you may have been told that you had a chemical imbalance, and that you needed tablets to correct it.

It’s not just doctors that think this way, either.

Magazines, newspapers, patients’ organisations and internet sites have all publicised the idea that conditions like depression, anxiety, schizophrenia and bipolar disorder can be treated by drugs that help to rectify an underlying brain problem.

People with schizophrenia and other conditions are frequently told that they need to take psychiatric medication for the rest of their lives to stabilise their brain chemicals, just like a diabetic needs to take insulin.

The trouble is there is little justification for this view of psychiatric drugs.

Altered states

First, although ideas like the serotonin theory of depression have been widely publicised, scientific research has not detected any reliable abnormalities of the serotonin system in people who are depressed.

Second, it is often said the fact that drug treatment “works” proves there’s an underlying biological deficiency.

But there is another explanation for how psychiatric drugs affect people with emotional problems.

It is frequently overlooked that drugs used in psychiatry are psychoactive drugs, like alcohol and cannabis.

Psychoactive drugs make people feel different; they put people into an altered mental and physical state.

They affect everyone, regardless of whether they have a mental disorder or not.

Therefore, an alternative way of understanding how psychiatric drugs affect people is to look at the psychoactive effects they produce.

Drugs referred to as antipsychotics, for example, dampen down thoughts and emotions, which may be helpful in someone with psychosis.

Drugs like Valium produce a state of relaxation and a pleasant drowsiness, which may reduce anxiety and agitation.

Drugs labelled as “anti-depressants” come from many different chemical classes and produce a variety of effects.

Prior to the 1950s, the drugs that were used for mental health problems were thought of as psychoactive drugs, which produced mainly sedative effects.

‘Informed choice’

Views about psychiatric drugs changed over the course of the 1950s and 1960s.

They gradually came to be seen as being specific treatments for specific diseases, or “magic bullets”, and their psychoactive effects were forgotten.

However, this transformation was not based on any compelling evidence.

In my view it remains more plausible that they “work” by producing drug-induced states which suppress or mask emotional problems.

If we gave people a clearer picture drug treatment might not always be so appealing

This doesn’t mean psychiatric drugs can’t be useful, sometimes.

But, people need to be aware of what they do and the sorts of effects they produce.

At the moment people are being encouraged to believe that taking a pill will make them feel better by reversing some defective brain process.

That sounds good. If your brain is not functioning properly, and a drug can make it work better, then it makes sense to take the pill.

If, on the other hand, we gave people a clearer picture, drug treatment might not always be so appealing.

If you told people that we have no idea what is going on in their brain, but that they could take a drug that would make them feel different and might help to suppress their thoughts and feelings, then many people might choose to avoid taking drugs if they could.

On the other hand, people who are severely disturbed or distressed might welcome these effects, at least for a time.

People need to make up their own minds about whether taking psychoactive drugs is a useful way to manage emotional problems.

To do this responsibly, however, doctors and patients need much more information about the nature of psychiatric drugs and the effects they produce.

Dr Moncrieff’s book “The Myth of the Chemical Cure”, published by Palgrave Macmillan, will be available in paperback from September.

Seroxat and the myth of the ‘chemical cure’ – dead in the water

Here is a VERY good article from the up & coming (Feb 8th) issue of Newsweek. It explodes the myths of the ‘chemical cure’ and ‘chemical imbalance’ once and for all.

I have challenged Glaxo many times before through these pages to tell me exactly how Seroxat actually works. They can’t tell me.

I have asked what the ‘correct’ brain level of Serotonin is. It can’t be measured.

I have asked them how brain levels of Serotonin can be measured in living humans. It can’t be measured.

And a new drug, tianeptine, which is sold in France and some other countries (but not the U.S.), turns out to be as effective as Prozac-like antidepressants that keep the synapses well supplied with serotonin. The mechanism of the new drug? It lowers brain levels of serotonin. “If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it,” says Kirsch, “it’s hard to imagine how the benefits can be due to their chemical activity.”

Here’s the article by  Sharon Begley – I’ve reproduced here in its entirety for ease of reading and reference:

Although the year is young, it has already brought my first moral dilemma. In early January a friend mentioned that his New Year’s resolution was to beat his chronic depression once and for all. Over the years he had tried a medicine chest’s worth of antidepressants, but none had really helped in any enduring way, and when the side effects became so unpleasant that he stopped taking them, the withdrawal symptoms (cramps, dizziness, headaches) were torture. Did I know of any research that might help him decide whether a new antidepressant his doctor recommended might finally lift his chronic darkness at noon?

The moral dilemma was this: oh, yes, I knew of 20-plus years of research on antidepressants, from the old tricyclics to the newer selective serotonin reuptake inhibitors (SSRIs) that target serotonin (Zoloft, Paxil, and the granddaddy of them all, Prozac, as well as their generic descendants) to even newer ones that also target norepinephrine (Effexor, Wellbutrin). The research had shown that antidepressants help about three quarters of people with depression who take them, a consistent finding that serves as the basis for the oft-repeated mantra “There is no question that the safety and efficacy of antidepressants rest on solid scientific evidence,” as psychiatry professor Richard Friedman of Weill Cornell Medical College recently wrote in The New York Times. But ever since a seminal study in 1998, whose findings were reinforced by landmark research in The Journal of the American Medical Association last month, that evidence has come with a big asterisk. Yes, the drugs are effective, in that they lift depression in most patients. But that benefit is hardly more than what patients get when they, unknowingly and as part of a study, take a dummy pill—a placebo. As more and more scientists who study depression and the drugs that treat it are concluding, that suggests that antidepressants are basically expensive Tic Tacs.

Hence the moral dilemma. The placebo effect—that is, a medical benefit you get from an inert pill or other sham treatment—rests on the holy trinity of belief, expectation, and hope. But telling someone with depression who is being helped by antidepressants, or who (like my friend) hopes to be helped, threatens to topple the whole house of cards. Explain that it’s all in their heads, that the reason they’re benefiting is the same reason why Disney’s Dumbo could initially fly only with a feather clutched in his teeth—believing makes it so—and the magic dissipates like fairy dust in a windstorm. So rather than tell my friend all this, I chickened out. Sure, I said, there’s lots of research showing that a new kind of antidepressant might help you. Come, let me show you the studies on PubMed.

It seems I am not alone in having moral qualms about blowing the whistle on antidepressants. That first analysis, in 1998, examined 38 manufacturer-sponsored studies involving just over 3,000 depressed patients. The authors, psychology researchers Irving Kirsch and Guy Sapirstein of the University of Connecticut, saw—as everyone else had—that patients did improve, often substantially, on SSRIs, tricyclics, and even MAO inhibitors, a class of antidepressants that dates from the 1950s. This improvement, demonstrated in scores of clinical trials, is the basis for the ubiquitous claim that antidepressants work. But when Kirsch compared the improvement in patients taking the drugs with the improvement in those taking dummy pills—clinical trials typically compare an experimental drug with a placebo—he saw that the difference was minuscule. Patients on a placebo improved about 75 percent as much as those on drugs. Put another way, three quarters of the benefit from antidepressants seems to be a placebo effect. “We wondered, what’s going on?” recalls Kirsch, who is now at the University of Hull in England. “These are supposed to be wonder drugs and have huge effects.”

The study’s impact? The number of Americans taking antidepressants doubled in a decade, from 13.3 million in 1996 to 27 million in 2005.

To be sure, the drugs have helped tens of millions of people, and Kirsch certainly does not advocate that patients suffering from depression stop taking the drugs. On the contrary. But they are not necessarily the best first choice. Psychotherapy, for instance, works for moderate, severe, and even very severe depression. And although for some patients, psychotherapy in combination with an initial course of prescription antidepressants works even better, the question is, how do the drugs work? Kirsch’s study and, now, others conclude that the lion’s share of the drugs’ effect comes from the fact that patients expect to be helped by them, and not from any direct chemical action on the brain, especially for anything short of very severe depression.

As the inexorable rise in the use of antidepressants suggests, that conclusion can’t hold a candle to the simplistic “antidepressants work!” (unstated corollary: “but don’t ask how”) message. Part of the resistance to Kirsch’s findings has been due to his less-than-retiring nature. He didn’t win many friends with the cheeky title of the paper, “Listening to Prozac but Hearing Placebo.” Nor did it inspire confidence that the editors of the journal Prevention & Treatment ran a warning with his paper, saying it used meta-analysis “controversially.” Al-though some of the six invited commentaries agreed with Kirsch, others were scathing, accusing him of bias and saying the studies he analyzed were flawed (an odd charge for defenders of antidepressants, since the studies were the basis for the Food and Drug Administration’s approval of the drugs). One criticism, however, could not be refuted: Kirsch had analyzed only some studies of antidepressants. Maybe if he included them all, the drugs would emerge head and shoulders superior to placebos.

Kirsch agreed. Out of the blue, he received a letter from Thomas Moore, who was then a health-policy analyst at George Washington University. You could expand your data set, Moore wrote, by including everything drug companies sent to the FDA—published studies, like those analyzed in “Hearing Placebo,” but also unpublished studies. In 1998 Moore used the Freedom of Information Act to pry such data from the FDA. The total came to 47 company-sponsored studies—on Prozac, Paxil, Zoloft, Effexor, Serzone, and Celexa—that Kirsch and colleagues then pored over. (As an aside, it turned out that about 40 percent of the clinical trials had never been published. That is significantly higher than for other classes of drugs, says Lisa Bero of the University of California, San Francisco; overall, 22 percent of clinical trials of drugs are not published. “By and large,” says Kirsch, “the unpublished studies were those that had failed to show a significant benefit from taking the actual drug.”) In just over half of the published and unpublished studies, he and colleagues reported in 2002, the drug alleviated depression no better than a placebo. “And the extra benefit of antidepressants was even less than we saw when we analyzed only published studies,” Kirsch recalls. About 82 percent of the response to antidepressants—not the 75 percent he had calculated from examining only published studies—had also been achieved by a dummy pill.

The extra effect of real drugs wasn’t much to celebrate, either. It amounted to 1.8 points on the 54-point scale doctors use to gauge the severity of depression, through questions about mood, sleep habits, and the like. Sleeping better counts as six points. Being less fidgety during the assessment is worth two points. In other words, the clinical significance of the 1.8 extra points from real drugs was underwhelming. Now Kirsch was certain. “The belief that antidepressants can cure depression chemically is simply wrong,” he told me in January on the eve of the publication of his book The Emperor’s New Drugs: Exploding the Anti-depressant Myth.

The 2002 study ignited a furious debate, but more and more scientists were becoming convinced that Kirsch—who had won respect for research on the placebo response and who had published scores of scientific papers—was on to something. One team of researchers wondered if antidepressants were “a triumph of marketing over science.” Even defenders of antidepressants agreed that the drugs have “relatively small” effects. “Many have long been unimpressed by the magnitude of the differences observed between treatments and controls,” psychology researcher Steven Hollon of Vanderbilt University and colleagues wrote—”what some of our colleagues refer to as ‘the dirty little secret.’ ” In Britain, the agency that assesses which treatments are effective enough for the government to pay for stopped recommending antidepressants as a first-line treatment, especially for mild or moderate depression.

But if experts know that antidepressants are hardly better than placebos, few patients or doctors do. Some doctors have changed their prescribing habits, says Kirsch, but more “reacted with anger and incredulity.” Understandably. For one thing, depression is a devastating, underdiagnosed, and undertreated disease. Of course doctors recoiled at the idea that such drugs might be mirages. If that were true, how were physicians supposed to help their patients?

Two other factors are at work in the widespread rejection of Kirsch’s (and, now, other scientists’) findings about antidepressants. First, defenders of the drugs scoff at the idea that the FDA would have approved ineffective drugs. (Simple explanation: the FDA requires two well-designed clinical trials showing a drug is more effective than a placebo. That’s two, period—even if many more studies show no such effectiveness. And the size of the “more effective” doesn’t much matter, as long as it is statistically significant.) Second, doctors see with their own eyes, and feel with their hearts, that the drugs lift the black cloud from many of their depressed patients. But since doctors are not exactly in the habit of prescribing dummy pills, they have no experience comparing how their patients do on them, and therefore never see that a placebo would be almost as effective as a $4 pill. “When they prescribe a treatment and it works,” says Kirsch, “their natural tendency is to attribute the cure to the treatment.” Hence the widespread “antidepressants work” refrain that persists to this day.

Drug companies do not dispute Kirsch’s aggregate statistics. But they point out that the average is made up of some patients in whom there is a true drug effect of antidepressants and some in whom there is not. As a spokesperson for Lilly (maker of Prozac) said, “Depression is a highly individualized illness,” and “not all patients respond the same way to a particular treatment.” In addition, notes a spokesperson for Glaxo-Smith-Kline (maker of Paxil), the studies analyzed in the JAMA paper differ from studies GSK submitted to the FDA when it won approval for Paxil, “so it is difficult to make direct comparisons between the results. This study contributes to the extensive research that has helped to characterize the role of antidepressants,” which “are an important option, in addition to counseling and lifestyle changes, for treatment of depression.” A spokesperson for Pfizer, which makes Zoloft, also cited the “wealth of scientific evidence documenting [antidepressants’] effects,” adding that the fact that antidepressants “commonly fail to separate from placebo” is “a fact well known by the FDA, academia, and industry.” Other manufacturers pointed out that Kirsch and the JAMA authors had not studied their particular brands.

Even Kirsch’s analysis, however, found that antidepressants are a little more effective than dummy pills—those 1.8 points on the depression scale. Maybe Prozac, Zoloft, Paxil, Celexa, and their cousins do have some non-placebo, chemical benefit. But the small edge of real drugs compared with placebos might not mean what it seems, Kirsch explained to me one evening from his home in Hull. Consider how research on drugs works. Patient volunteers are told they will receive either the drug or a placebo, and that neither they nor the scientists will know who is getting what. Most volunteers hope they get the drug, not the dummy pill. After taking the unknown meds for a while, some volunteers experience side effects. Bingo: a clue they’re on the real drug. About 80 percent guess right, and studies show that the worse side effects a patient experiences, the more effective the drug. Patients apparently think, this drug is so strong it’s making me vomit and hate sex, so it must be strong enough to lift my depression. In clinical-trial patients who figure out they’re receiving the drug and not the inert pill, expectations soar.

That matters because belief in the power of a medical treatment can be self-fulfilling (that’s the basis of the placebo effect). The patients who correctly guess that they’re getting the real drug therefore experience a stronger placebo effect than those who get the dummy pill, experience no side effects, and are therefore disappointed. That might account for antidepressants’ slight edge in effectiveness compared with a placebo, an edge that derives not from the drugs’ molecules but from the hopes and expectations that patients in studies feel when they figure out they’re receiving the real drug.
The boy who said the emperor had no clothes didn’t endear himself to his fellow subjects, and Kirsch has fared little better. A nascent collaboration with a scientist at a medical school ended in 2002 when the scientist was warned not to submit a grant proposal with Kirsch if he ever wanted to be funded again. Four years later, another scientist wrote a paper questioning the effectiveness of antidepressants, citing Kirsch’s work. It was published in a prestigious journal. That ordinarily brings accolades. Instead, his department chair dressed him down and warned him not to become too involved with Kirsch.

But the question of whether antidepressants—which in 2008 had sales of $9.6 billion in the U.S., reported the consulting firm IMS Health—have any effect other than through patients’ belief in them was too important to scare researchers off. Proponents of the drugs have found themselves making weaker and weaker claims. Their last stand is that antidepressants are more effective than a placebo in patients suffering the most severe depression.

So concluded the JAMA study in January. In an analysis of six large experiments in which, as usual, depressed patients received either a placebo or an active drug, the true drug effect—that is, in addition to the placebo effect—was “nonexistent to negligible” in patients with mild, moderate, and even severe depression. Only in patients with very severe symptoms (scoring 23 or above on the standard scale) was there a statistically significant drug benefit. Such patients account for about 13 percent of people with depression. “Most people don’t need an active drug,” says Vanderbilt’s Hollon, a coauthor of the study. “For a lot of folks, you’re going to do as well on a sugar pill or on conversations with your physicians as you will on medication. It doesn’t matter what you do; it’s just the fact that you’re doing something.” But people with very severe depression are different, he believes. “My personal view is the placebo effect gets you pretty far, but for those with very severe, more chronic conditions, it’s harder to knock down and placebos are less adequate,” says Hollon. Why that should be remains a mystery, admits coauthor Robert DeRubeis of the University of Pennsylvania.

Like every scientist who has stepped into the treacherous waters of antidepressant research, Hollon, DeRubeis, and their colleagues are keenly aware of the disconnect between evidence and public impression. “Prescribers, policy-makers, and consumers may not be aware that the efficacy of [antidepressants] largely has been established on the basis of studies that have included only those individuals with more severe forms of depression,” something drug ads don’t mention, they write. People with anything less than very severe depression “derive little specific pharmacological benefit from taking medications. Pending findings contrary to those reported here … efforts should be made to clarify to clinicians and prospective patients that … there is little evidence to suggest that [antidepressants] produce specific pharmacological benefit for the majority of patients.”
Right about here, people scowl and ask how anti-depressants—especially those that raise the brain’s levels of serotonin—can possibly have no direct chemical effect on the brain. Surely raising serotonin levels should right the synapses’ “chemical imbalance” and lift depression. Unfortunately, the serotonin-deficit theory of depression is built on a foundation of tissue paper. How that came to be is a story in itself, but the basics are that in the 1950s scientists discovered, serendipitously, that a drug called iproniazid seemed to help some people with depression. Iproniazid increases brain levels of serotonin and norepinephrine. Ergo, low levels of those neurotransmitters must cause depression. More than 50 years on, the presumed effectiveness of antidepressants that act this way remains the chief support for the chemical-imbalance theory of depression. Absent that effectiveness, the theory hasn’t a leg to stand on. Direct evidence doesn’t exist. Lowering people’s serotonin levels does not change their mood. And a new drug, tianeptine, which is sold in France and some other countries (but not the U.S.), turns out to be as effective as Prozac-like antidepressants that keep the synapses well supplied with serotonin. The mechanism of the new drug? It lowers brain levels of serotonin. “If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it,” says Kirsch, “it’s hard to imagine how the benefits can be due to their chemical activity.”

Perhaps antidepressants would be more effective at higher doses? Unfortunately, in 2002 Kirsch and colleagues found that high doses are hardly more effective than low ones, improving patients’ depression-scale rating an average of 9.97 points vs. 9.57 points—a difference that is not statistically significant. Yet many doctors increase doses for patients who do not respond to a lower one, and many patients report improving as a result. There’s a study of that, too. When researchers gave such nonresponders a higher dose, 72 percent got much better, their symptoms dropping by 50 percent or more. The catch? Only half the patients really got a higher dose. The rest, unknowingly, got the original, “ineffective” dose. It is hard to see the 72 percent who got much better on ersatz higher doses as the result of anything but the power of expectation: the doctor upped my dose, so I believe I’ll get better.

Something similar may explain why some patients who aren’t helped by one antidepressant do better on a second, or a third. This is often explained as “matching” patient to drug, and seemed to be confirmed by a 2006 federal study called STAR*D. Patients still suffering from depression after taking one drug were switched to a second; those who were still not better were switched to a third drug, and even a fourth. No placebos were used. At first blush, the results offered a ray of hope: 37 percent of the patients got better on the first drug, 19 percent more on their second, 6 percent more improved on their third try, and 5 percent more on their fourth. (Half of those who recovered relapsed within a year, however.)

How does STAR*D validate the idea that the key to effective treatment of depression is matching the patient to the drug? Maybe. Or maybe people improved in rounds two, three, and four because depression sometimes lifts due to changes in people’s lives, or because levels of depression tend to rise and fall over time. With no one in STAR*D receiving a placebo, it is not possible to conclude with certainty that the improvements in rounds two, three, and four were because patients switched to a drug that was more effective for them. Comparable numbers might have improved if they had switched to a placebo. But STAR*D did not test for that, and so cannot rule it out.

It’s tempting to look at the power of the placebo effect to alleviate depression and stick an “only” in front of it—as in, the drugs work only through the placebo effect. But there is nothing “only” about the placebo response. It can be surprisingly enduring, as a 2008 study found: “The widely held belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking,” scientists wrote in the Journal of Psychiatric Research. The strength of the placebo response drives drug companies nuts, since it makes showing the superiority of a new drug much harder. There is a strong placebo component in the response to drugs for pain, asthma, irritable-bowel syndrome, skin conditions such as contact dermatitis, and even Parkinson’s disease. But compared with the placebo component of antidepressants, the placebo response accounts for a smaller fraction of the benefit from drugs for those disorders—on the order of 50 percent for analgesics, for instance.
Which returns us to the moral dilemma. In any year, an estimated 13.1 million to 14.2 million American adults suffer from clinical depression. At least 32 million will have the disease at some point in their life. Many of the 57 percent who receive treatment (the rest do not) are helped by medication. For that benefit to continue, they need to believe in their pills. Even Kirsch warns—in boldface type in his book, which is in stores this week—that patients on antidepressants not suddenly stop taking them. That can cause serious withdrawal symptoms, including twitches, tremors, blurred vision, and nausea—as well as depression and anxiety. Yet Kirsch is well aware that his book may have the same effect on patients as the crows did on Dumbo when they told him the “magic feather” wasn’t really giving him the power of flight: the little elephant began crashing to earth. Friends and colleagues who believe Kirsch is right ask why he doesn’t just shut up, since publicizing the finding that the effectiveness of antidepressants is almost entirely due to people’s hopes and expectations will undermine that effectiveness.

It’s all well and good to point out that psychotherapy is more effective than either pills or placebos, with dramatically lower relapse rates. But there’s the little matter of reality. In the U.S., most patients with depression are treated by primary-care doctors, not psychiatrists. The latter are in short supply, especially outside cities and especially for children and adolescents. Some insurance plans discourage such care, and some psychiatrists do not accept insurance. Maybe keeping patients in the dark about the ineffectiveness of antidepressants, which for many are their only hope, is a kindness.

Or maybe not. As shown by the explicit criticism of drug companies by the authors of the recent JAMA paper, more and more scientists believe it is time to abandon the “don’t ask, don’t tell” policy of not digging too deeply into the reasons for the effectiveness of antidepressants. Maybe it is time to pull back the curtain and see the wizard for what he is. As for Kirsch, he insists that it is important to know that much of the benefit of antidepressants is a placebo effect. If placebos can make people better, then depression can be treated without drugs that come with serious side effects, not to mention costs. Wider recognition that antidepressants are a pharmaceutical version of the emperor’s new clothes, he says, might spur patients to try other treatments. “Isn’t it more important to know the truth?” he asks. Based on the impact of his work so far, it’s hard to avoid answering, “Not to many people.”

Is Clinical Depression Caused by a Serotonin Imbalance?

This from Chemical Imbalance.org (thanks to Truthman30):

“In a sense there are two entirely different discussions going on about the theory: In the media and the advertisements serotonin deficiency is presented as simple and straightforward, but in scientific circles it is treated as tenuous at best.  In scientific circles the debate seems to be not so much about the strength of the theory but about the appropriateness of using it with patients given the lack of clear data – one prominent academic psychiatrist states that the serotonin theory is a metaphor which he will not use with his own patients; another practicing psychiatrist states that that the evidence presented by Dr. Kramer “doesn’t mean much” in clinical practice but admits to telling patients they have a chemical imbalance all the same.

We continue to wonder if the scientific evidence justifies such behavior, let alone massive marketing campaigns which inform the general public that depression is the result of a serotonin imbalance. In the matter of informed consent, we question whether patients who are told they have a chemical imbalance really understand how little direct evidence there is for the theory.”

[Now read on:]

Is Clinical Depression Caused by a Serotonin Imbalance? A Response to Peter Kramer

Jonathan Leo, Ph.D.
Jeffrey Lacasse, Ph.D.

INTRODUCTION

The claim that depression is caused by an imbalance of serotonin is often made in the mainstream media. In a recent paper in Society we report on our efforts to examine the supporting evidence used by journalists who make such claims. We corresponded with a pharmaceutical company, several psychiatrists, and the National Institute of Mental Health. For the most part we received few citations of scientific papers, and those that were cited did not provide evidence for a causal connection between serotonin and depression. In our experience, there are few scientists familiar with the data that will publicly defend the serotonin theory of depression.

We also believe that debate between researchers holding conflicting viewpoints is an essential part of scientific progress. We were therefore pleased to see that Peter Kramer, author of Listening to Prozac, recently posted a defense of the theory on his blog. Dr. Kramer had previously made public comments responding to critiques of the serotonin theory in 2006, stating, “While it’s true that one could say that these drug companies are using a very oversimplified metaphor – and a metaphor for something that may not even exist at all – it’s also wrong to suggest that it has no relationship to contemporary theories of mood regulation.

Since we agreed with this statement, we were intrigued by Dr. Kramer’s recent defense of the serotonin theory. In his blog posting, Dr. Kramer cites evidence to support the serotonin theory, much of it from a recent review article in the New England Journal of Medicine. All of the studies Kramer discusses are interesting research projects, but for us, the important question is: Do these studies provide enough scientific evidence to support the ubiquitous statements in the media about depression?  As just a few examples:  “Mental illness are simply chemical imbalances,” or “Depression is thought to be caused by a chemical imbalance in the brain.” Below, we analyze the evidence presented.

ANALYSIS OF CITED STUDIES

Alteration in 5-HT1B Receptor Function by p11 in Depression-Like States (2006) Science, 311: p77. In reference to this paper, Kramer states: “Other studies have found that serotonin receptors function less efficiently in depressed patients. A protein named p11 is implicated: depressed patients have less of it in the brain.”  The paper in question is a four page paper that examines the interaction of the serotonin 1B receptor with p11 in rodents. Out of the four pages, the authors devote one sentence to p11 in humans. In what can only be called a preliminary report, as very few details are supplied, the authors report that p11 mRNA is decreased in the anterior cingulate cortex in patients who suffered from depression (p.79). The study used fifteen patients and fifteen controls. Seven of the patients committed suicide. Patients who commit suicide are very likely not a fair representation of the average patient diagnosed with depression, but this problem aside, the authors do not mention whether the patients had a history of medication exposure – an obvious question.

An e-mail inquiry and subsequent reply from E. Fuller Torrey, the head of the Stanley Foundation, which supplied the brains for the study, confirmed that the majority of the patients had been prescribed medication – whether they filled these prescriptions and/or took the medications is unknown. Dr. Torrey did mention that one possibility is that the patients who committed suicide stopped taking their medication, implying that the lack of medication was a contributing factor to their suicide. Thus the lower level of p11 in the depressed patients could be due to long-term antidepressant use, to the withdrawal effect, or to a combination of both. Therefore, a major piece of evidence that Kramer uses to defend the serotonin theory is a comparison of 15 patients with a history of medication use, which was only one minor component of a larger study.  We do not think that our concern with prior medication use is excessive. In the words of Ross Baldessarini, professor of psychiatry,  “Almost any psychotropic drug that’s given for more than a few weeks leads to changes in brain function such that when you stop, the brain has to reset its thermostat.”

Major Depressive Disorder, New England Journal of Medicine (NEJM), 358:55. In this review article, the authors discuss numerous avenues of research into depression. While the authors discuss serotonin they do not supply any direct evidence for the idea that low serotonin is the cause of depression. For instance, they discuss tryptophan depletion studies. Tryptophan is a rate limiting enzyme involved in serotonin production in the brain. It was originally hypothesized that tryptophan depletion would lead to low serotonin, which in turn would lead to a lowering of mood. Yet, as the authors point out, in healthy subjects this has not been the case.

The authors also discuss an oft-cited study by Caspi et al. which investigated common polymorphisms of the promoter for the serotonin transporter gene.  Yet, the NEJM’s piece also includes the oft-made characterization about the study, which leaves out some important details. According to the NEJM, “Caspi et al. found that 5-HTTTLPR predicted depression only in association with defined life stresses” (p. 56).  However, this needs to be qualified by pointing out two important points: 1) Just the presence of the short form of the gene did not predict depression – after all following major life stressors only 35% of the short form carriers developed depression (If 65% of the carriers do not develop depression, it seems hard to characterize it as predictive). One needs to qualify the statement in the NEJM by saying that carriers of the short form were more likely than carriers of the long form to develop depression after major life stressors (It is the comparison that is important). Yet, besides pointing out that it is the difference between long and short form that is important, even more qualifications are warranted. 2) In addition, “defined life stressors” must be qualified; the carriers of the short form were at a disadvantage only if they were exposed to three or more major life stressors.  For those people who only suffered one or two life stressors, the findings were reversed and the patients with the short form actually were less likely to be depressed – in this case the short form was protective (See Figure 3, p. 389 of the Caspi study). A subsequent study by Shelley Taylor and her colleagues at UCLA found that people with two copies of the gene’s short form were actually less likely to have depression symptoms if they had positive childhood experiences.

Also of note with the Caspi study is that the marker in question is not a rare mutation found in only a small percentage of the population. Approximately 70% of the population carries this “susceptibility” gene. One possible conclusion is that they have not discovered something unique about the subset of people diagnosed with depression, but have discovered something about human nature in general. Of course there are mechanisms in the makeup of the human brain that respond to environmental stressors. But finding these mechanisms does not mean that we have found a marker for a disease. If 70% of us have a gene that plays a role in our response to stress should this be considered “normal” or “pathological?” Complicating interpretation of this data, while some studies have found similar results to Caspi, other groups have not (Gillespie, 2005).

Kramer also touches on the efficacy of the SSRIs when he says, “The NEJM notes that a third of depressed patients do not respond to antidepressants. In those who do respond, what the authors call ‘the monoamine-deficiency hypothesis extended’ remains the most powerful explanation of the drugs’ mechanism of action.” Leaving efficacy aside, it is important to point out that showing how a drug acts at the molecular level does not necessarily equate to understanding the etiology of a condition – in this case determining that a drug acts on the serotonin receptor or serotonin system does not prove that depression is caused by low serotonin. If we followed the logic that “mechanism equals disease” then we could assume that every drug with a behavioral effect on the nervous system does so because of a chemical imbalance – something which is certainly not true. In many cases a drug will relieve a symptom but not treat the root cause of the problem. Take a long distance runner with a pulled muscle. Pain medication will relieve the pain – a symptom – but we do not attribute the cause of the pulled muscle to a chemical imbalance. Many drugs – both legal and illegal – act on the monoamine system: SSRIs, amphetamines, methylphenidate [Ritalin], mushrooms, coffee, cocaine, etc.

The authors of the NEJM piece state: “A strong point of the monoamine theory is its predictive power. Almost every compound that has been synthesized or discovered for the purpose of inhibiting norepinephrine or serotonin reuptake has been proved to be a clinically effective antidepressant.” We would go one step further and point out that based on the predictive power of the monoamine theory, even though the legal and illegal drugs have similar pharmacological properties, the chemical imbalance theory will only be applied to the use of drugs sold by a pharmaceutical company. Take the performance enhancing effects of amphetamines. If they are sold by a pharmaceutical company to improve classroom performance in a child this is considered acceptable, but selling amphetamines to a baseball player seeking to increase his batting average, can get you five to ten – and the player can wind up unemployed. The justification for the difference between the two scenarios? One case involves treatment for a supposed chemical imbalance, and one case involves a cheater. The demarcation between the two scenarios is not based on the pharmacological profile of amphetamines but on marketing and societal mores.

Elevated Monoamine Oxidase A Levels in the Brain: An Explanation for the Monoamine Imbalance of Major Depression,” Archives of General Psychiatry, 63, 1209-1216. This is one of the more interesting papers on this topic. MAO-A is an enzyme that breaks down the neurotransmitters serotonin, norepinephrine, and dopamine. The authors’ hypothesis is that MAO-A levels are higher in the brain during untreated depression, which they believe could explain the monoamine theory of major depression. They used positron emission tomography (PET) scanning on 17 patients diagnosed with depression and 17 healthy patients, and measured their levels of MAO-DVs, an indicator of MAO-A. The group of depressed patients had higher mean (average) levels of MAO-A. Thus, one interpretation is that these higher levels of MAO-A enzymes cause major depression. After critically appraising this paper, we have several questions:

Does this paper establish that increased MAO-A is the cause of major depression? Or, alternatively, does it simply document an association? We wonder if higher mean MAO-A among a group of depressives might be a sign of depression, rather than the cause. Consider that many people get nervous before public speaking, and, frequently, their heart rate quickens and their blood pressure goes up. But most people would not say that high blood pressure is the biochemical explanation for public speaking anxiety. Similarly, how do we know that lower MAO-A in depressed individuals is not simply a sign of depression, rather than the cause? Certainly, further experiments are required before causal claims can be made regarding MAO-A in depression.

Have the results been replicated? The answer is no. This is a study of 17 depressives and 17 healthy patients in Canada. Time will tell if independent research teams are able to replicate this finding with other patients. Certainly, important findings should be replicated, repeatedly, by as many different research teams as possible. The history of science, and in particular psychiatric science, is full of exciting preliminary findings followed by failed replication attempts.

Are the results specific to depression? Keep in mind that MAO does not just break down serotonin, but also norepinephrine and dopamine. These three neurotransmitters are implicated in almost every DSM-IV-defined mental disorder. In future experiments, rather than healthy volunteers, it would be interesting to see patients diagnosed with major depression compared to patients diagnosed with other non-affective mental disorders (e.g., ADHD). Until such experiments are performed, we think many will question whether these findings are specific to depression.

Below, we have created a figure with content similar to figure 2, p.1212, in their article. (We cannot reproduce the original figure due to copyright). This figure is most similar to the results presented for the midbrain, hippocampus, and putamen. The pattern holds true less so for the results from the posterior cingulated cortex and thalamus.

What do we make of the fact that there is overlap between healthy and depressed patients? Several healthy patients have higher levels of MAO-A than depressed patients, and some depressed patients have lower levels of MAO-A than healthy patients. For instance, in the figure above, if we consider that the healthy patients have “normal” levels of MAO-A, then eight out of the seventeen depressed patients would fall in the normal range, or conversely 7 of the healthy patients would fall in the same range as the depressed patients. In other words, while there might be differences in group means, this does not mean that individual patients can be identified on the basis of their MAO-A levels. This is quite different than the diagnosis of diabetes, a medical condition to which clinical depression is often compared, in which lab tests are used to accurately diagnose patients.

Are the author’s conclusions congruent with the existing clinical trial data? Recent research has challenged the efficacy of SSRIs. For instance, a recent systematic review concluded, “Among adults with moderate to severe major depression in the clinical trials we reviewed, paroxetine was not superior to placebo in terms of overall treatment effectiveness and acceptability” (Barbui, Toshiaki, & Cirpiani, 2008, p. 296). We are confused as to how such findings line up with the proposal that serotonin imbalance causes depression. Michael Thase, an academic psychiatrist and pharmaceutical company-funded clinical trialist, has proposed that one or two out of ten patients prescribed an SSRI have a clinically significant response. Would proponents of the chemical imbalance theory interpret this to mean that 80-90% of patients prescribed SSRIs do not have a serotonin imbalance?

To top it all off, there are many debatable issues regarding statistical reporting, generalizability, and the other issues that face all such small neuroimaging studies.

Thus, while the Meyer study is an interesting piece of research, and is an important contribution to the field (and we certainly look forward to seeing future reports of MAO) we do question using it, as Kramer does, as primary evidence in support of the idea that depression is caused by low serotonin. In other words, the problem lies not with the ongoing laboratory research, but with prematurely drawing conclusions from these data.

CONCLUSION

We are pleased that Kramer has put in writing what he thinks is the best evidence for the serotonin theory, however, we are concerned that readers of his blog may mistakenly conclude that there is indeed powerful new evidence for the serotonin theory. As we have shown, an in-depth look at these studies finds the results to be tentative, at best. Hypotheses regarding serotonin and depression have been generated that need to be rigorously tested, as has been the case for forty years.

Overall, this discussion illustrates the difficulties of the scientific process and the perils of justificationary thinking. If a psychiatrist begins with the belief that serotonin deficiency causes depression and proceeds from there, there will always be studies to be cited. Unfortunately, much of this evidence collapses under critical scrutiny.

We would prefer a more rigorous scientific model. Important components would include replication, acceptance and integration of counter-evidence, active attempts to falsify the theory being tested, and a solid grasp of the methodological limitations involved with the research. Fortunately, we find that most scientists are quite aware of these limitations. In fact, when scientists discuss the biological basis of mood with other scientists, it is almost as if there are a set of ground rules that everyone agrees with, such as: (a) There are extremely subtle nuances to many of these studies; (b) it is important to refrain from drawing too many conclusions from the latest findings; (c) finding a biological difference between people diagnosed with depression and “normals” does not automatically warrant the jump to causation; and (d) environmental triggers play an extremely important role in why someone’s mood might be lowered. Yet, in the popular press all these qualifications disappear and instead the public is inundated with declarations that “mental disorders are caused by chemical imbalances.”

In a sense there are two entirely different discussions going on about the theory: In the media and the advertisements serotonin deficiency is presented as simple and straightforward, but in scientific circles it is treated as tenuous at best.  In scientific circles the debate seems to be not so much about the strength of the theory but about the appropriateness of using it with patients given the lack of clear data – one prominent academic psychiatrist states that the serotonin theory is a metaphor which he will not use with his own patients; another practicing psychiatrist states that that the evidence presented by Dr. Kramer “doesn’t mean much” in clinical practice but admits to telling patients they have a chemical imbalance all the same.

We continue to wonder if the scientific evidence justifies such behavior, let alone massive marketing campaigns which inform the general public that depression is the result of a serotonin imbalance. In the matter of informed consent, we question whether patients who are told they have a chemical imbalance really understand how little direct evidence there is for the theory.

We encourage reporters to dig deeper and to question whether the evidence in support of the theory justifies simplistic claims about the cause of depression, and to carefully consider the claims made by  psychiatrists and other experts about the serotonin theory. In his blog posting, Kramer argues that the miserably depressed Zoloft Ovoid creature is smarter than the critics have made him or her out to be. We agree with Kramer that the Ovoid is intelligent, however, given its ability to convince the media that there is substantial evidence in support of the serotonin theory, it appears that the Ovoid’s talents seem to lie in the marketing, and not the scientific, realm.

Glaxo – a simple challenge for you…

It’s been a while since I wrote anything as I’ve been very busy with my day job.

Happily, others have continued to write – I’ve just read a post over at Seroxat Suffers about Glaxo in New Zealand and the Patient Information Leaflet that comes with Aropax (Seroxat).

According to Glaxo (only in New Zealand, though):

Depression is longer lasting or more severe than the low moods that everyone has from time to time. It is thought to be caused by a chemical imbalance in parts of the brain.

AROPAX corrects the chemical imbalance and so helps relieve the symptoms of depression.

Sorry, but I have to throw the gauntlet down to Glaxo on this one… I think in 2012 it’s fair to say that the chemical imbalance story has been discredited completely.

But, Glaxo, if you can tell me what the correct level of Serotonin is in a human brain, then I’ll listen.

If you can measure how much Serotonin I currently have in my brain, then I’ll listen.

If you can then demonstrate how much 20mgs of Seroxat will raise my brain serotonin level by, then I’ll listen.

But the problem is that Glaxo can’t do any of those – the idea of a ‘chemical imbalance’ causing depression – and even the term ‘SSRI’ – was invented by marketing and PR companies, simply to sell a drug.

To use a technical term, it’s complete bollocks.

 

 

Research repeatedly shows that antidepressants give little benefit – but have many side effects

So, slowly, slowly the mainstream media seems to be catching up with what we’ve known for quite a while – the drugs don’t work, we’ve just been told they do.

If you follow this argument to source, then you have to question the drug companies about the way they run their drug trials and the way the way they market their (all too often) sub-standard and dangerous drugs – Glaxo, amongst many others, has a track record of hiding negative clinical trial data that would knock sales of its drugs – the story of Seroxat and Study 329 is truly shocking.

This from today’s Independent:

What if the drugs don’t work?

Research repeatedly shows that antidepressants give little benefit – but serious side effects. Yet millions who take them regard them as lifesavers. Markie Robson-Scott reports on the controversy that is dividing psychiatrists.

When my American friend Bill, who’d been on SSRI antidepressants for 22 years (Prozac, followed by Paxil, Lexapro, then Celexa), read a two-part article by Dr Marcia Angell in The New York Review of Books recently about the crisis in psychiatry and the inefficacy of antidepressants, he stopped taking his meds (tapering off gradually, monitored by his doctor). “The article brought on enough doubt to push me over,” he said. Since then, his moods have become more volatile – more anger, more emotion, such as crying at the end of the last Harry Potter film (he’s in his 50s). But he’s got his libido back after years of “muffled response” and that seems a worthwhile trade-off.

Instead of listening to Prozac, have we been listening to placebo all along? Research repeatedly appears to show that: antidepressants are little more than placebos, with very little therapeutic benefit but serious side-effects (70 per cent of people on Celexa and Paxil report sexual dysfunction, and in some, it carries on even when they stop taking the pills). The theory of chemical imbalance as a cause of depression is an unproven hypothesis; and doctors are prescribing the drugs mainly because of the “juggernaut of pharmaceutical promotion”, as the US psychiatrist Dr Daniel Carlat calls it.

It’s not surprising there’s a US media furore – about 10 per cent of Americans over the age of six take antidepressants. In the UK, prescriptions for the drugs went up 43 per cent in the last four years to 23 million a year.

Professor Irving Kirsch, associate director of the programme in placebo studies at Harvard Medical School and author of The Emperor’s New Drugs: Exploding the Antidepressant Myth, says the theory of chemical imbalance – that there is not enough serotonin, norepinephrine and/or dopamine in the brain synapses of depressed people – doesn’t fit the data (lowering serotonin levels in healthy patients has no impact on their moods). Chemical imbalance is a myth, he says. It follows that the idea that “antidepressants can cure depression chemically is simply wrong”. His meta-analysis of 38 clinical studies – 40 per cent of which had been withheld from publication because drug companies didn’t like the results – involving more than 3,000 depressed patients on SSRIs shows that only 25 per cent of the benefit of antidepressant treatment was due to the drugs and that 50 per cent was a placebo effect. “In other words, the placebo effect was twice as large as the drug effect,” though the placebo response was lower in the severely depressed.

This is not quite as damning as it sounds: placebos are extraordinarily powerful and can be “as strong as potent medications”. Placebo response is specific: placebo morphine eases pain, placebo antidepressants relieve depression. It’s a question of expectancy and conditioning: if you expect to feel better, you will, even if you’re getting negative side effects, because side effects, Kirsch says, convince people that they’ve been given a potent drug.

Psychotherapy boosts the placebo effect and is “significantly more effective than medication” for all levels of depression, he says. Antidepressants should only be used “as a last resort and only for the most severely depressed”.

Of course, not everyone agrees. Ian Anderson, Professor at psychiatry at the University of Manchester, who is to debate whether “antidepressants are useful in the treatment of depression” with Kirsch at a conference in Turkey next month, thinks we’re in danger of throwing the baby out with the bathwater when we say antidepressants are rubbish. Antidepressants are part of a doctor’s toolbox, though probably most useful for the most depressed; some people don’t take to talking therapies; it’s not an either/or situation, he says.

Professor Allan Young, chair of psychiatry at Imperial College London, agrees. “Depression is such a huge category of illness – there are multiple types, and each type responds differently.” Of course, the brain and the body are inextricably linked, he says, and placebo effects are greater in the less-severely ill.

To make things more complicated, there’s the nocebo effect. If you expect to feel bad when you come off antidepressants, you will, because “we tend to notice random small negative changes and interpret them as evidence that we are in fact getting worse”, Kirsch says.

Lucy, who was suicidal, took Cipramil (Celexa in the US) on and off for 10 years. She says the drug “gave me back myself, it was like a ray of light shining through fog”, but the side effects – nausea and lost libido among others – forced her off it. Then “it was like a clock ticking, a twitch in the back of my mind. I lived in fear of the depression coming back. The only thing that kept me alive was knowing the pills were there. But was it because I believed I was a depressive so when I had the negative feelings I panicked?”

For Judy, lofepramine, a tricyclic, worked well. “First I was given Prozac, which gave me huge anxiety, like a bad trip, and made me horribly aware of all my nerve-endings. But lofepramine worked from the first day. When I took it in the morning I’d get a chemical lift, like a switch being turned on: it was a fabulous rush of joy.”

She stopped taking it after six months. Several months later, she felt low, though not depressed – “I feel depression like a stone in my solar plexus, and it wasn’t like that. But still I thought it would be nice to have that short-cut to happiness, so I took a lofepramine and it had no effect whatsoever – because I wasn’t really depressed. So to me the placebo theory makes no sense.” Neither does it to Hannah, who took Prozac for 10 years and says “it was absolutely fantastic and saved my life”.

Daniel Carlat, a psychiatrist in Boston and author of Unhinged: The Trouble with Psychiatry – A Doctor’s Revelations about a Profession in Crisis says that prescribing is a hit-and-miss affair. “Unfortunately we know a good bit less about what we are doing than you might think,” he writes. “When I find myself using phrases like ‘chemical imbalance’ and ‘serotonin deficiency’, it is usually because I’m trying to convince a reluctant patient to take a medication. Using these words makes their illness seem more biological, taking some of the stigma away.”

Most lay people, he says, don’t realise how little shrinks know about the underpinning of mental illness, though he’s not as convinced as Kirsch about the placebo effect and makes the point that the patients who turn up at his office are different from those recruited into clinical trials because drug companies, desperate to get their product to outperform a placebo, are picky about who they choose.

You have to have “pure” depression, unblemished by alcohol use, anxiety problems, bipolar disorder, suicidal thoughts, mild or long-term depression – which, says Carlat, would exclude most of his patients. Yet, as Marcia Angell, author of The Truth About the Drug Companies: How They Deceive Us and What to Do About It, says: “It’s true… but they are the best we have.”

If there’s one thing that’s clear among the contradictions, it’s that the brain remains mysterious. As Carlat says: “Undoubtedly, there are neurobiological and genetic causes for all mental disorders, but they are still beyond our understanding.” All we really know is that depression exists and that sometimes the drugs seem to work – even if it’s a placebo effect.

Antidepressants: the guidelines

* Never stop taking antidepressants without discussing it with your doctor, because abrupt cessation of SSRIs can cause withdrawal symptoms that can be both physical and mental.

* If you do decide to stop, you’ll need to reduce the dose gradually rather than stopping abruptly.

* If you’re happy with your antidepressant and you feel it works for you, then keep on taking it. Regular use is what works: if it ain’t broke, don’t fix it, says Professor Irving Kirsch.

Confirmation that there is a difference between Seroxat/Paxil and other SSRIs

A very topical subject this – it seems that Seroxat is actually different from other SSRIs… but I’m worried that it has come just too late.

Before you read this article please bear in mind that no-one actually knows just how SSRIs work – the hypothesis of chemical imbalance has been exposed as a lie.

However, what this new research does seem to point to is that Seroxat/Paxil acts in a different way to other SSRIs – perhaps this could explain why Seroxat/Paxil is so hard to stop taking?

The most widely prescribed antidepressants — medicines such as Prozac, Lexapro and Paxil — work by blocking the serotonin transporter, a brain protein that normally clears away the mood-regulating chemical serotonin. Or so the current thinking goes.

That theory about how selective serotonin reuptake inhibitors (SSRIs) work can now be put to the test with a new mouse model developed by neuroscientists at Vanderbilt University.

These mice, described in the online edition of the Proceedings of the National Academy of Sciences (PNAS), express a serotonin transporter that has been genetically altered so that it does not respond to many SSRIs or cocaine.

In addition to testing the theory about how SSRIs work, the new mouse model could lead to the development of entirely new classes of antidepressant medications, said Randy Blakely, Ph.D., Allan D. Bass Professor of Pharmacology and Psychiatry at Vanderbilt and senior author of the PNAS paper.

“Many antidepressants have been shown to target other proteins besides the serotonin transporter and … their efficacy in treating depression takes many weeks to develop,” Blakely said. “There is likely a lot that we don’t know about how these drugs act.”

To generate the mouse model, Blakely and colleagues at Vanderbilt and the University of Texas Health Science Center at San Antonio first determined exactly which parts of the serotonin transporter protein interact with SSRIs. They took advantage of the fact that the fruit fly expresses a serotonin transporter that is relatively insensitive to the drugs.

By changing the protein’s amino acid building blocks, they converted parts of the human serotonin transporter into its fruit fly equivalent, and in so doing identified the single amino acid required for potent binding to many SSRIs as well as to cocaine.

As predicted, the genetically-modified mice displayed normal serotonin transporter levels, and their transporter exhibited normal activity in clearing serotonin from the synapses between nerve cells. But the mice did not respond to Prozac or Lexapro, indicating that the transporter is indeed the specific target of these medications for blocking serotonin inactivation.

“Interestingly, one SSRI, paroxetine (Paxil), retains its normal powerful action on the transporter, revealing that — at a molecular level — different antidepressants interact with the transporter in different ways,” Blakely said.

The researchers are now evaluating chronic administration of SSRIs to determine how much the transporter contributes to the more clinically relevant, delayed effects of these drugs, as well as for the side effects experience with antidepressant medications.

Because the serotonin transporter in the mouse also lost cocaine sensitivity, the model also may help researchers determine exactly how cocaine acts in the brain. “Perhaps what started as a hunt for better ways to treat depression may also spill over into a better understanding of addiction,” Blakely said.

Brent Thompson, Ph.D., is the first author of the PNAS paper. Blakely directs the Center for Molecular Neuroscience and the Silvio O. Conte Center for Neuroscience Research at Vanderbilt.

Douglas McMahon, Ph.D., professor of Biological Sciences and Pharmacology at Vanderbilt, also collaborated on the research, which was supported by the National Institutes of Health.

How drug companies re-engineer illness to keep making money

In this interview with Christopher Lane (from Psychology Today), David Healy outlines just a few of the ways way drug companies market their pills…

David Healy, a former secretary of the British Association for Psychopharmacology, is the author of over 120 articles and 14 books, including The Antidepressant Era, The Creation of Psychopharmacology, and Mania, a fascinating new book on the history of bipolar disorder. His criticism of drug-company practices has put him at odds with colleagues in psychiatry and pharmacology. At the same time, his undisputed expertise as a leading academic, researcher, and clinician gives him a unique perspective on patterns and problems in Anglo-American psychiatry. He recently agreed to answer a number of questions about the growing prevalence and expanded definition of bipolar disorder.

Part of what you describe in your new book Mania: A Short History of Bipolar Disorder is a fair amount of “biomythology” about the illness. What aspects in particular do you have in mind?

Biomythology links to biobabble, a term I coined in 1999 to correspond to the widely-used expression psychobabble. Biobabble refers to things like the supposed lowering of serotonin levels and the chemical imbalance that are said to lie at the heart of mood disorders, ADHD, and anxiety disorders. This is as mythical as the supposed alterations of libido that Freudian theory says are at the heart of psychodynamic disorders.

While libido and serotonin are real things, the way these terms were once used by psychoanalysts and by psychopharmacologists now—especially in the way they have seeped into popular culture—bears no relationship to any underlying serotonin level or measurable chemical imbalance or disorder of libido. What’s astonishing is how quickly these terms were taken up by popular culture, and how widely, with so many people now routinely referring their serotonin levels being out of whack when they are feeling wrong or unwell.

In the case of bipolar disorder the biomyths center on ideas of mood stabilization. But there is no evidence that the drugs stabilize moods. In fact, it is not even clear that it makes sense to talk about a mood center in the brain. A further piece of mythology aimed at keeping people on the drugs is that these are supposedly neuroprotective—but there’s no evidence that this is the case and in fact these drugs can lead to brain damage.

How does our understanding of “mania” differ today from earlier conceptions of the phenomenon?

Bipolar disorder itself is a somewhat mythical entity. As used now the term bears little relation to classic manic-depressive illness, which required people to be hospitalized with an episode of illness, either depression or mania. The problems that currently are grouped under the heading “bipolar disorder” are akin to problems that, in the 1960s and 1970s, would have been called “anxiety” and treated with tranquilizers or, during the 1990s, would have been labeled “depression” and treated with antidepressants.

How did we move so rapidly in the 1990s from a psychotherapeutic treatment model for children to a largely drug-related one?

I think a key factor in this shift has been the availability of operational criteria. These were introduced in 1980 in DSM-III, the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders. The idea was to bridge the gap between the psychotherapists, on the one hand, and the neuroscientists on the other. It was hoped that if both camps could ensure that patients met 5 of 9 criteria for depression, for instance, then at least the patient groups would be homogenous, even if the views on what had led to the problems weren’t.

It was still assumed, however, that there was a place for clinical judgment, so that a patient who met 5 of the 9 criteria for depression but had ‘flu or was pregnant would be diagnosed as being pregnant rather than depressed. But in the face of company marketing, and with the advent of the Internet, clinical judgment has been eroded. Patients going on the Internet or faced with drug company materials now all too easily find that they meet criteria for a disorder and there is often nothing or no-one to tell them this is not equivalent to having the disorder.

In the extreme, I have had patients with highly social careers come to me and say they think they have Asperger’s Syndrome because they’ve been on the Internet and find that they meet the criteria for this when, in fact, almost by definition, such a person cannot have Asperger’s Syndrome. In the absence of clinical judgment there is a default towards a biological option and a drug solution. Criteria create a problem for which a drug is all too often the answer, in just the same way that measurements of your lipid levels create a problem that a statin is the answer to.

Operational criteria are interacting here with a certain loss of medical authority. It is not possible for a doctor today to say to a patient, “Based on my 15 to 20 years experience, you do not have PTSD,” or whatever. She cannot say, “We do not need to continue this conversation; come back when you’ve had a medical training and 15 years of clinical experience.”

The doctor has to engage with the patient on the level of the material that’s out there in popular culture, and when she tries to do this she will find that she’s up against an extraordinarily skilful deployment of those materials by pharmaceutical company marketing departments who are masters at populating the wider culture to suit their interests.

In the mid-1990s, you note, roughly half of all mood disorders were redefined as bipolar disorder rather than depression. What do you think accounts for that dramatic shift in perspective?

The key event in the mid-1990s that led to the change in perspective was the marketing of Depakote by Abbott as a mood stabilizer. Before that, the concept of mood stabilization didn’t exist. And while in a popular TV series we can accept that Buffy the Vampire Slayer gets a new sister in Season Five that she had all the time but we didn’t know about, we don’t expect this to happen in academia.

The introduction of mood stabilization by Abbott and other companies who jumped on the bandwagon to market anticonvulsants and antipsychotics was in fact quite comparable to Buffy getting a new sister. Mood stabilization didn’t exist before the mid-1990s. It can’t be found in any of the earlier reference books and journals. Since then, however, we now have sections for mood stabilizers in all the books on psychotropic drugs, and over a hundred articles per year featuring mood stabilization in their titles.

In the same way, Abbott and other companies such as Lilly marketing Zyprexa for bipolar disorder have re-engineered manic-depressive illness. While the term bipolar disorder was there since 1980, manic-depression was the term that was still more commonly used until the mid-1990s when it vanishes and is replaced by bipolar disorder. Nowadays, over 500 articles per year feature bipolar disorder in their titles.

You just have to look at Lilly’s marketing of Donna from the Zyprexa documents on the Internet to see what is going on here: “Donna is a single mom, in her mid-30s, appearing in your office in drab clothing and seeming somewhat ill at ease. Her chief complaint is ‘I feel so anxious and irritable lately.’ Today she says she has been sleeping more than usual and has trouble concentrating at work and at home. However, several appointments earlier she was talkative, elated, and reported little need for sleep. You have treated her with various medications including antidepressants with little success. . . You will be able to assure Donna that Zyprexa is safe and that it will help relieve the symptoms she is struggling with.”

Donna could have featured in ads for tranquilizers from the 1960s to the 80s, or for antidepressants in the 1990s, and would have probably been more likely to respond to either of these treatment groups than to an antipsychotic, and less likely to be harmed by them than by an antipsychotic. What company marketers are so good at doing is framing the common symptoms people have—we almost all have—in a manner most likely to lead to a prescription for the remedy of the day. It flies in the face of a century of psychiatric thinking to see conditions that patients like Donna have as bipolar disorder. But while a century of psychiatric thinking used to count for something, it doesn’t any longer.

Between 1996-2001, you explain, there was a fivefold increase in the use of antipsychotics (Zyprexa, Risperdal, Abilify, Seroquel, and others) in preschoolers and preteens. What role did DSM-IV play in that, with its introduction of the still-controversial category Bipolar II disorder?

The concept of juvenile bipolar disorder flies even more in the face of traditional wisdom in psychiatry than does calling Donna bipolar. As of 2008, upwards of a million children in the United States—in many cases preschoolers—are on “mood-stabilizers” for bipolar disorder, even though the condition remains unrecognized in the rest of the world.

I am not sure how much DSM-IV played a role in this switch. I think the companies would have found a way to engineer the switch even without the introduction of Bipolar II disorder in DSM-IV.

So then how much of that shift is attributable to SSRI antidepressants coming off patent while the antipsychotics were still major revenue earners?

I think this was in fact central to what happened. The antidepressants were due to come off patent whereas the anticonvulsants were older drugs that could be repatented for this purpose, and the antipsychotics—which also could be (and were) marketed as mood stabilizers—were early in their patent life.

A related point that’s worth bringing out is that the switch happened because companies weren’t able to make new and more effective antidepressants. Had they been able to do so, I think they would have probably stuck with the depression model rather than made the switch to bipolar disorder.

In terms of what is happening in the US, I think we have to look at how skillfully the drug companies have exploited doctors. Doctors have wanted to help. While the drugs are available on prescription only, doctors tend to see giving a medicine as the way to go, where previously they had been much more skeptical about the benefits of drug treatments.

The drug companies have engineered a situation in which academics have become the primary spokespeople for the drugs. We see the sales rep in the corner and think we can easily resist his or her charms—but we still let them pick up the drinks tab. But it’s the academics who sell the drugs. Doctors who think they are uninfluenced by company marketing listen to the voices of academic psychiatrists when these, in the case of the antidepressants or antipsychotics given to children, have talked about the data from controlled trials, and by doing so have been witting or unwitting mouthpieces for company marketing departments.

In your opinion, did the FDA’s 2004 decision to add black-box warnings to SSRIs over pediatric use lead to greater off-label prescriptions and even the move toward antipsychotics, on the presumption that the latter are safer to use on children?

I think this had very little effect on the switch from depression to bipolar disorder, but what was quite striking was how quickly companies were able to use the views of the few bipolar-ologists who argued that when children become suicidal on antidepressants it’s not the fault of the drug. The problem, they said, stems from a mistaken diagnosis and if we could just get the diagnosis right and put the child on mood stabilizers then there wouldn’t be a problem.

There is no evidence for this viewpoint, but it was interesting to see how company support could put wind in the sails of such a perspective.

It was also interesting to see how close to delusional people could get about an idea like this. Faced with details such as even healthy volunteers becoming suicidal on an antidepressant, committed bipolar-ologists were quite ready to say that this just shows that these normal people are latently bipolar.

In this case, I think most people will see that “latent bipolarity,” as a concept, is functioning a little bit  like the way latent homosexuality once functioned for the Freudians. Most people will also see that the first concept is impossible. What the companies have done is hand a megaphone to the proponents of that view on bipolar disorder, which was until very recently a distinctly minority one.

And are the antipsychotics in fact safer than antidepressants?

No, they are not. The antipsychotics are as dangerous as the antidepressants. Before the introduction of the antipsychotics, the rates of suicide in schizophrenia were extremely low—they were hard to differentiate from the rest of the population. Since the introduction of the antipsychotics the rates of suicide have risen 10- or 20-fold.

Long before the antidepressants were linked with akathisia, the antipsychotics were universally recognized as causing this problem. It was also universally accepted that the akathisia they induce risked precipitating the patient into suicidality or violence.

They also cause a physical dependence. Zyprexa is among the drugs most likely to cause people to become physically dependent on it. As far as I am concerned, Zyprexa’s license for supposed maintenance treatment in bipolar disorder stems from data that is in fact excellent evidence for the physical dependence it causes and the problems that can arise when the treatment is stopped.

In addition, of course, these drugs are known to cause a range of neurological syndromes, diabetes, cardiovascular problems, and other problems. It’s hard to understand how blind clinicians can get to problems like these, especially in youngsters who grow obese and become diabetic right before their eyes.

But we have a field which, when faced with the obvious, instead chose to listen to Eli Lilly voices saying, “Oh no, there is no problem with Zyprexa. The psychosis is what causes diabetes—Henry Maudsley recognized that 130 years ago.” Well Henry Maudsley hated patients, and saw very few of them at a time when diabetes was rare. We recently looked at admissions to the North Wales Hospital from 1875-1924, years spanning his career, and among the more than 1,200 cases admitted for serious mental illness, not one had diabetes and none went on to develop it.

We also looked at admissions to the local mental-health unit between 1994 and 2007, and in over 400 first admissions none had type 2 diabetes, but the group as a whole went on to develop diabetes at twice the national rate.

This is not surprising. What is is how the entire field swallowed the Lilly line, especially when it was so implausible to begin with. We had great difficulties getting this article published—one journal refused even to have it reviewed.

One way of raising the profile of bipolar disorder in children, you note, was to argue that they’d been misdiagnosed with ADHD. What were the implications and effects of that claim?

In the case of children with ADHD, I think what one needs to appreciate is that in most of the world until very recently (and in countries like India still), ADHD is a very rare disorder where children, usually boys, are physically very overactive. This is a condition they grow out of in their teens. Treatment with a stimulant can make a difference in cases like this. Whether treatment is always called for, however, may depend on the circumstances of the child as opposed to the nature of any supposed condition.

It is only in a world where schooling or adherence to a particular set of social norms is compulsory that a condition like ADHD becomes a disorder. There was greater scope over a century ago than there is now for children to do other things in childhood and wait until they settled down in adolescence without being treated for their condition.

What we have today is not ADHD as it was classically understood, but rather a state of affairs we have had for centuries, which is “the problem child.” Today the problem child is labeled as having ADHD. But having just one label is very limiting. Child psychiatry needed another disorder—and for this reason bipolar disorder was welcome.

Not all children find stimulants suitable, and just as with the SSRIs and bipolar disorder it has become very convenient to say that the stimulants weren’t causing the problem the child was experiencing; the child in fact had a different disorder and if we could just get the diagnosis correct, then everything else would fall into place.

One fascinating phenomena at the moment is a clear looping effect with adult ADHD. Quite recently Britain’s NICE [National Institute for Health and Clinical Excellence] guidelines for ADHD came out and stated that adult ADHD is a valid clinical disorder. I am quite sure that a few years ago, 85 to 90 percent of physicians in the UK would not have thought adult ADHD was a valid clinical disorder. One might expect guidelines to be somewhat conservative, but in this case what we appear to be seeing is the guideline process getting out ahead of the field, leading clinicians in a direction that seems to be quite surprising.

Drug companies understand all too well that those constructing guidelines are supposed to be value-neutral and to follow the data. This means they can readily engineer trials that may show minimal benefit for their drug for a condition they have called “adult ADHD.” The makers of the guidelines have little option but to suspend judgment and to accept that the condition named must be real. So, for instance, as Lilly grasped, they end up endorsing the use of the agent like Strattera.

What’s astonishing about the current situation is that there seems to be almost no way to get the guideline makers—who are sitting in the middle of the road, immobilized by the oncoming headlights—out of the way of the pharmaceutical juggernaut. You can point out how they are being manipulated but they shrug and ask, “What can we do?”

We have recently begun a survey, here in North Wales, looking at aspects of this situation. In response to questions, clinicians here have indicated that three years ago they were quite certain they would not have used adult ADHD as a valid condition, but that three years from now they anticipate that they probably will. I think this shows a realistic appreciation of company abilities to change the climate in which clinical practice takes place, and the relative futility of attempting to stand up to such changes.

You have to treat real patients. What do you tell them about these conditions and their treatment options?

Many clinicians, scientists, and patients have heard about postmodernism. They might have heard company criticism of someone like me along such lines as “Pay no heed to him, he’s just a postmodernist.” The implication is that postmodernism is all-but a psychiatric disorder in its own right, in which academics like me refuse to concede that there’s any reality to human behaviors—or the physical underpinnings of disorders of human behavior. By contrast, the story goes, there are the hard scientists who work in or with drug companies who deal only with facts and hard data, and the proof is that they bring new and helpful drugs to the market.

Well, I think what Donna’s story above illustrates is that pharmaceutical marketing departments are actually the postmodernists par excellence. They treat the human body (including its disorders and complaints) as texts to be interpreted one way this year and in just the opposite way a year or two later.

In contrast, when it comes to the hazards of these drugs—just like the tobacco companies before them—the motto of Pharma has become “doubt is our product”—they simply refuse to concede that their drugs are linked to any hazard at all . . . until the drug goes off patent. You cannot get a better definition of postmodernism than “doubt is our product.”

So, to the matter of whose treatments are better: I’m quite happy that the patients coming to see me would in general get more effective and safer treatment for their problems than they’d get from physicians adhering to the latest guidelines. Trouble is, I only have to slip up once to have a big problem, whereas atrocities can be committed on the other side without anyone likely to be affected by blowback.

David Healy is the author of 14 books, including The Antidepressant Era, The Creation of Psychopharmacology, Let Them Eat Prozac: The Unhealthy Relationship between the Pharmaceutical Industry and Depression, and, most recently, Mania: A Short History of Bipolar Disorder. Christopher Lane is the author most recently of Shyness: How Normal Behavior Became a Sickness.

Seroxat and alcohol, Paxil and alcohol…

Do you know what really amazes me?… I’ll tell you then.

It is the fact that Glaxo continues to say there is nothing wrong with Paxil (Seroxat) – and that if you do suffer from withdrawal then the “discontinuation symptoms” that can occur in some people will be “generally short lived” and “mild to moderate in intensity”.

Glaxo says “We take the reporting of adverse effects very seriously, as we do with all our medications. Fortunately, with Seroxat, we have a wealth of positive experience involving thousands of physicians and millions of patients – over ten years of experience worldwide.”

Then why can Glaxo continue to IGNORE the tens of thousands of reports of “negative experience” – such as adverse drug reactions and the huge mass of anecdotal reports of severe problems while taking (and withdrawing from) Paxil?

WHY?

Below are comments posted to an article called Pax-ills – What Every Paxil User Needs to Know. It made even me sit up and take notice. (Read more comments here)

You’ll notice the dates – 2003/2004/2005… nothing new here, so Glaxo has had plenty of time to “take the reports seriously” – and yet it has done nothing:

Anonymous (March 11, 2003): Please tell me I’m not the only Paxil patient who has developed an intense craving for alcohol. I am hangover-free (which was never the case when I indulged on a weekend) and am drinking every day. It’s ruining my life but no one else seems to believe it’s the Paxil.

Amy (April 22, 2003): I just want to warn the public about the side effects from stopping the vile drug, Paxil. I have been on it for almost 3 years for GAD. When I decided to go off, my dr. gave me the instructions for “weaning” myself off the drug. I did exactly what she had told me to do, and within a week of weening, I started to get these horrible side effect. They included: Brain “zaps”, confusion, crying spells, dizziness, and a list of many other things. I called my Dr back, and let her know about this. She told me that it was just depression, and to go back on Paxil. I tried to explain to her that I was not on Paxil for depression, (This was not the original dr. that prescribe the drug to me), I was on it for GAD, and the feelings that I was having, were NOT the same feelings that I had before I started taking Paxil in the first place. I am still trying to “wean” myself off the drug, without the help of any dr., and it has been over 3 months now. I just want to stop taking it, but every time I go off, the side effects continue. No one can seem to help me.

Please, if you can help it, DO NOT go on this vile drug. While it did help me when I was on it, it is impossible to go off.

Anyone who is experiencing the same thing, there is a website called paxildatabase.com in this website, there is a petition that you can sign for the drug maker.

Nicole (May 14, 2003): Re: Paxil withdrawal–I’ve been through it, and while it isn’t my favorite experience, future withdrawal fears shouldn’t prevent anyone suffering a major depression from trying this drug or other SSRIs. I was put on Paxil for after being hospitalized for depression in 1999 and had almost three good years on it, with minimal depressive symptoms. It literally gave me my life back! Unfortunately, it seemed to be gradually losing its efficacy earlier this year (the typical poop-out thing many people experience) resulting in a second severe episode of depression. Going off the Paxil (to switch to Effexor, which I’m glad to say is working pretty well) was uncomfortable–I had “electric” “zingy” feelings in my head, muscle cramps, anxiousness for about two weeks–but not at all intolerable (certainly nothing compared to being severely depressed). More like having the flu. It’s a minor price to pay for three years of relief–Truly.

Newzmel (May 25, 2003): I am currently on Paxil and have been on and off it for about ten years. Initially, I was diagnosed as unipolar; thanks to three weeks without sleep on the new Paxil CR, I am now diagnosed as bipolar. I too get brain zaps, as well as bugs crawling in my stomach. The regular paxil made me anorexic, no appetite whatsoever. I have never had a problem getting off it, in fact, feel *great* for about two months after. Then BOOM, back to the Paxil. I have tried other antidepressants, but this one seems to work the best. I’m told it’s good for anxiety, but I notice my panic level is heightened on the drug. I’ve tried Celexa, Prozac and the most heinous of the bunch: Zoloft. I felt like my arms were on backwards. Paxil may work for some for three years Nicole, but what about these horrible side effects????

PPH (June 16, 2003): I tool Paxil from July 1996 through November 2000. Prior to taking the drug, I exhibited symptoms of depression including insomnia and frequent crying. These symptoms quickly went away when a doctor prescribed Paxil. However, there was one side effect. Prior to Paxil, I rarely drank alcohol. This changed quickly, I began drinking heavily within two months of beginning Paxil. It was something that I couldn’t control. I always thought there was a connection, but I couldn’t find any evidence to support this theory. The drinking continued with heavy consequences. Finally, after entering rehab in November 2000, I begged them to switch my medication (I had to beg because they still didn’t think it was contributing to the drinking). They did switch me to Zoloft. Today, I still don’t drink, and I lost that insane urge to drink that I had while on the Paxil.

Dolfingrl (Aug 18, 2003): Help…My husband has been on Paxil for two years and I have noticed a DRASTIC change in his personality. He has become insensitive and prone to anger…he used to be a a very caring and mild mannered person, but now is prone to violent (verbal) outbursts and is quick to lose his temper. He has difficulty controlling his anger and communicating in the normal manner. Please tell me if this is normal???

PRP (Aug 25, 2003): To all user of Paxil, my husband was on Paxil for 8 months, he was a wonder husband & father. A church member, member to masonic lodge and self-employed. Our life changed 8/21/02 when he blacked out, and got a gun and I was almost killed myself, himself, along with a family friend. The gun was fired 4-times,he then went to our couch, and his eyes where going back & forth (as I was told), I was knocked out. He then grabbed a blackjack and beat me till he came too. Then I blacked out again and I came too. I saw him with a 357 gun point to our friend’s head. He was charged with 2nd degree attempted murder and all that comes with that. To make this a shorter story, all charges were dropped because there was only Paxil in his system. He as well was a victim. We are suing GSK And we are very happy now .My husband has no memory of this event. It will live with us forever.

Luz (Sept 19, 2003): I found this thread because I was specifically searching for info on Seroxat (Paxil) and alcohol cravings. I have been on Seroxat for 5 or 6 years now, and have been drinking more with less apparent effect (until I (occasionally) black out & lose my memory) during that time. What I have noticed is that when I tried (unsuccessfully, because of withdrawal symptoms) to reduce or stop the dosage, my cravings for alcohol pretty much disappear. I am not talking about alcoholism but this level of drinking is deeply worrying to me. I understand the legal disclaimers on this thread, so I would point out that obviously this is just my particular case, but it is extremely interesting to me to see that others have had similar side effects.

Smilin’ Scott (Dec 17, 2003): I have had an increase craving for alcohol, morning hand tremors or shakes, and electric shock sensation on different parts of my body first thing in the morning. Anyone else have these things?

SSC (Dec 26, 2003): I am so glad I found this site. I, too have been searching the web for Paxil and alcohol cravings info. My cravings became so intense that it has ruined my life. I told my doctor about he cravings but he said it was not from the Paxil. I began drinking every day-large amounts. I have since lost my job, went to rehab. and am facing 2 counts of DUI and will loose my license and go to jail. I am so scared! I never had trouble with the law or drinking before. Plus, I live in a small town and everyone thinks I am the town drunk as all of this was posted in our local paper. I have been humiliated. I am also in jeopardy of loosing my current job because of my legal situation. I went off the Paxil and guess what? No cravings. If anyone has any info that might help me show a link between Paxil and alcohol, please post! I am just glad to know I am not alone.

Kit (Jan 24, 2004): After reading this article, I was relieved to find other people having the same alcohol symptoms as myself. I didn’t know why for the past two years I couldn’t stop drinking. It has been awful! I am on a small dosage of Paxil (10mg) and cut down to 5 last weekend. I still drank all week and have had some mild withdrawal- headaches, weird dreams, sleeplessness, pounding heart, but nothing I can’t handle. Last night was the first night I didn’t crave alcohol. We went out to dinner, I had one glass of wine, and didn’t want another. It is now 5:30 pm and by now I’d have had a few, but I haven’t even wanted one. I am so excited. I’ll keep you posted as I continue to cut the Paxil out of my life. Stupid drug.

Quitter (Feb 2, 2004): Hi, I have been taking Paroxetine for a bit over 2 years to combat generalized anxiety disorder. I am now 4 days into my third attempt at quitting. It is a relief to find others who know what this feels like, the “zaps”, the dissociation, dizziness, and hopelessness. I started taking this drug because it had a short half-life and would hit my system quickly, a necessity because when I went to see the doctor, my anxiety was so powerful it had consumed my life.

Surfer Girl (Feb 7, 2004): My 19 year old daughter has been on Paxil for about 8 months. Her depression is worse, she is self injurious, angry, anxiety ridden, and cannot sleep. She has nightmares, and suicidal thoughts. I recently began to taper down her dosage, after checking her into a local mental hospital. She now has to attend partial day classes every day for 3 weeks. The hospital has given her a prescription for Effexor XR, to which I say NO THANKS. I want a therapist to work with my “drug free” daughter, not a suicidal induced, stressed out maniac. Withdrawal has been a problem also. I SEE NO BENEFIT TO PAXIL CR.

Now I want off. It is terrible to be ruled by a drug. I didn’t know it would be this hard. I was so uninformed, people need to know what can happen when they quit the “miracle drug”.

Kit (Feb 8, 2004): I wrote earlier about Paxil vs alcohol. I am now down to 2.5 mg of Paxil from 10 – which I know was not a large dose to begin with – and haven’t had a drink in 11 days and haven’t wanted one either. I thank God I found this site. I knew my crazy, out of control alcohol cravings didn’t just start on their own! I’ll be off Paxil soon – probably another week. I wait until the brain zaps stop, and then I go down another few mgs. I can’t go any lower, so I’ll be off of it. After awhile, maybe in a few months, I’ll have a glass of wine. If I can’t stop drinking, I’ll know I’m a booze bag and have to quit alcohol forever. If I can drink like I used to – one glass of wine being just fine – I’ll know it was the Paxil, for sure.

Smilin’ Scott (Feb 19, 2004): Has anyone else had realistic dreams? i am having a hard time with reality and dreams. also my memory isn’t as good as it used to be. I do feel more like my old self beside the alcohol cravings, dreams and memory and the “zapping.”

Anonymous (April 2, 2004): I rarely drank much until I began Paxil but noticed a higher tolerance. I went out one night and had 19 drinks. Mixed with my Paxil, I hit a police officer and am now facing 15 yr aggravated

assault charge. I am not a violent person. I don’t even know what happened and how I was able to drink so much without passing out. No one will even listen to me about this happening due to Paxil and increased alcohol consumption. Paxil has ruined my life and my families!!! Why

aren’t there alcohol warning labels on the sides of the bottle???? Sucks to be me!!!!!

Not Myself (April 13, 2004): After one more bizarre night out, I decided to look for information on Paxil CR and alcohol. Glad to find this site.

I have been taking Paxil CR for several months. Previously took Zoloft; should NEVER have switched! I’m going back– but, here’s what I’ve noticed!

1. Paxil leaves me feeling anxious… on the verge of depression and irrational thought, but not so much that I don’t recognize that it’s happening. I feel like crying every day, but I cannot cry.

2. I have insane and crazily vivid dreams. Last night, I woke with a scream and totally freaked out my pets! What’s more, there is a finer line between my reality and dream states… it’s very confusing. Too, my memory is awful.

3. I have gone out on the town a few times; I have been out of control! Just this weekend, I was wasted after one cocktail… but, I didn’t stop… went rapidly on to a 2nd and 3rd cocktail… moving into something of a dream state. I was detached, wildly aggressive and truly out-of-control! I was fortunate to have friends with me, so I suffered only embarrassment. I slept entirely through the next day… I’ve never, ever done that before. Three days later, I still feel abnormal.

There is DEFINITELY something wrong with my reactions to Paxil CR! For me, it’s confirmed!

Anna (April 16, 2004): Hi I have been on Seroxat for 5 1/2 years i have tryed coming off before and had the side effects such as feeling down anxious head zaps which i didn’t know then where actually side effects the Doctor told me it was my anxiety coming back and i was to up my dose I know realise that to get off seroxat you have to go through the withdrawal i am now using the liquid for and have gone from 30mg to 4mg it has taken 1 + 1/2 months the side effects are not that bad I will beat this. If you really want to get off this Drug get the liquid for its much easier to cut down with.

Chris (May 9, 2004): My wife takes Paxil CR for OCD, undiagnosed before we got married, and I loved her before starting the medication, but REALLY like it that she can now go kill her own ants, spiders, and cockroaches without me rushing home from work to do it for her. There are a lot of the same side-effects involved with her that were listed in the other stories- increased tolerance/ craving for alcohol and other carbohydrates, diarrhea after eating, etc… but with the hope of eventually getting off it and keeping the OCD in check post-Paxil CR, we’re all-in-all happy with the drug. It’s not for everybody. I work in medicine and know some of those doctors talked about in the other stories- “medication is the solution to everything”. It will seriously help anyone having trouble with this medication to have a really good friend there to help, like my wife says that I am for her. Good luck to you all!

G (May 17, 2004): I have been on Seroxat for about 6 years, and found it fixed my problems, except that my craving for alcohol increased a great deal (normally drink very little). It doesn’t give you a hangover in the morning either. I have managed to keep the drinking to the evenings, but spirits taste like water, and has very little effect until I fall asleep about 11:00 pm. I started on 20mg and I am now on 10mg. Trouble is I don’t want to get of it all together, only to have my symptoms come back, which were very unpleasant. The other articles are very interesting re drinking, think they all have a common cause.

Cathy (June 5, 2004): I am about to be getting a possible Article 15 in the US Army for 2 counts of assault and drunk and disorderly behavior.

– I have NEVER gotten violent while drinking; I’m what you would call a “happy, goofy” drunk.

– Sure, I’ve gotten drunk, but I’ve never drank to where I don’t even remember drinking and become so incapacitated. In other words- I can tell you how much I drank and know that I was getting drunk!

– My blood alcohol was a .29! I only remember drinking 3 beers! My friend said I was buying one stein of beer after another- I don’t even remember this – this is for the person who said they had 19 drinks and didn’t even realize it!!!

– Maybe those of us whose lives/careers/families are being ruined because of this can support one another and assist each other in a defense.

Herein lies the problems I’m trying to deal with:

1.) Personal Responsibility-

On my prescription bottle of medication it does have a label that says “Do not drink alcohol while taking this medication” – therefore I have no defense in this matter

but pleez!!!! Are you telling me that people that take Paxil do not drink AT ALL????

It was my understanding that the main reason you shouldn’t drink alcohol is mostly that it intensifies the drowsiness and reduces the effectiveness of the drug?

I was also told that a beer or 2 is okay – but geez, if there’s a way to prove that it can cause the craving for alcohol, then maybe I can help with my defense?

I’m so frustrated. Some people say I’m trying to make up excuses and blame it on the medication. I’m struggling with this –

how do I accept personal responsibility?

I need to find medical journals/studies – is there currently research being done on SSRI’s/increasing levels of serotonin in brain and link to craving alcohol?

Also- I’ve seen where Paxil has been used to TREAT ALCOHOLISM! Could it be that for some small percentage of the population- it actually does the OPPOSITE?

Yeah, I know what you mean- the guy who said he’s labeled the “town drunk”. It’s like it’s not bad enough that we’ve done something so out of character that we’ve shocked ourselves- but that people label us. People look at me with these disapproving looks. You can’t explain that this is not normal behavior for you! It’s so devastating the humiliation. I just want to scream YOU DON’T KNOW ME, YOU DON’T UNDERSTAND!!!! But they don’t.

They’re so quick to judge you negatively.

Jill (June 18, 2004): Well thank goodness ! I thought I was the only one with these symptoms. I used to have a couple of glasses on wine on the weekends, but after being on Paxil, I can drink wine like water. One to two bottles is not unusual for me at all. And I can get up the next day feeling normal, without even a headache. Why is that ? I have the strange dreams too and sometimes feel like I haven’t slept. To make matters worse, I have gained 10 lbs (most likely because of all the wine). I really am not happy with the way this pill is working at all.

Rick (June 20, 2004): I’ve been taking Paxil for over 5 years now. I’am bipolar and have had a fair amount of success with this drug. I am 44 years of age and have been fighting this wicked disease since I was 14.Back then Doctors knew very little about this disease and how to treat it. I’ve been on just about every medication out there. Paxil is the only drug to really help me although I’m not doing very well as I write this. Drinking over the years is something I have enjoyed and for the most part was able to control it. There are plenty of times when I drank more than I should have-but I usually knew when to call it a night and always got home safely. Drinking on Paxil is a different story. I never know when to stop because you don’t feel like your getting drunk until it’s way to late and I end up blacking out.

What is so amazing is I can drink more then I ever have and wake up like nothing happened-no hangover what so ever. I also know I should not be drinking while taking Paxil but I crave it more then I ever have before. I could never understand this and now that I have discovered this web site I know i’ts not just me. As I write this I find myself in the depression stage of bipolar and although I’ve been through this so many times before I’m not sure I will be around to see what comes of this. My life has been a roller coaster and I don’t know how much more I can take.

Luz (June 25, 2004): Re. my September ‘03 post on alcohol cravings. Since that post, I have finally managed to come off Paxil completely, and have been off the drug for 6 months now. I noticed a definite ’switch point’ in the withdrawal process where my alcohol cravings disappeared entirely, and they have never returned – I am overjoyed. I wonder whether the effect some of us report is a distortion of the carbohydrate cravings the drug is said to produce (hence the weight gain), but I think there is more to it than that; I could drink and drink and drink, as if I was seeking oblivion. I am back to being an occasional drinker with normal hangovers – Hurrah! I am afraid I don’t have any good advice to offer those still suffering these cravings, but I am thinking of you.

Lisa (July 16, 2004): I was wondering if anyone else was misdiagnosed with Bi-Polar disorder while on Paxil?

I have been taking it on, and off for 11 years. Last year my ex-Dr doubled my dosage from 20 to 40mgs of Paxil, and that is when I started having bi polar signs. Not sleeping, and going like the Duracell bunny followed by being exhausted with major thoughts of suicide. My life was a living hell. I finally found a Dr that listened, and told me I was being poisoned by the Paxil, and slowly I am getting my life back.

Another thing the Paxil did was mimic Auto Immune diseases, Anyone else have this problem. Thanks!

Karen (Oct 7, 2004): Following the recent Panaroma programme on the BBC, I am absolutely disgusted at the lack of integrity by Alastair Benbow & his organisation – many people have suffered and died at the hands of these people just for the sheer end of generating profit. My faith in the medical profession at large is at an all time low. In my capacity as an advertising executive, I will NEVER work with a pharmaceutical company. They are scum.

David (Oct 12, 2004): I have been very desperate lately and it seems that everything is falling into place after reading about Paxil and alcohol. I took Paxil for 3 years and had a number of episodes like what is mentioned here,i just figured it was me and my mental decline from a 45 day coma and my brain just giving up. I have since being on Paxil become suicidal, i have mutilated myself, I have sporadic violent outbursts (at 6′3 220lbs,its not pretty), I even smell alcohol I have an uncontrollable urge to just get wasted. I to like many got a dui and I consider it to me a godsend. My demeanor is not what I mentioned above but i just assumed it was my failure to cope. I have stopped taking the Paxil cr(37.5) and realize the good it did. I don’t remember things very well like were i set my keys, money, wallet. I “space out” a lot more and almost feel as if at any time i could be sleeping but awake like on that movie Looker. My point being Paxil is an evil drug that should be limited maybe to short term use. Open your eyes see the light and get off the Paxil. Thank you for your forum, it may have well saved my life or someone else’s for that matter. If you have any advise get back to me please. Thank You again McMan

PPP (Nov 5, 2004): I TAKE PAXIL CR I WENT TO A DINNER PARTY WITH MY HUSBAND DRINKING WINE BLACK OUT ALL I CAN REMEMBER IS WAKING THE NEXT MORNING HE SAID I EMBARRASSED SO BAD THAT HE DIDN’T SHOW HIS FACE AT WORK

Kathy (Nov 11, 2004): Thank you for this website & the luck of finding it! I am finally not alone. I have been taking 20mg Paxil daily for 3 years. FOr the last 6 months I have CRAVED white wine daily & drink approximately a bottle a day every night. In the last 3 months I have had watery stool after EVERY meal, and I have gained 20 lbs. I never thought it was Paxil related, I\’ve been on it so long without these side effects I figured it was a GI problem. So I finally went to a new MD. Her suggestion was to get a colonoscopy & increase the Paxil to 30mg a day. After reading all of the above, how can I get off this horrible drug without the terrible side effecs? Please help me.

MIndy (Nov 12, 2004): Paxil side effects I too want to report an increased craving for alcohol while on Paxil. I would take the medication and a few hours later just be dying to have a drink. I was always one that drank some but never to this extent. It got to the point where I was unable to get my work done. I went to my medical DR with this and he just laughed and looked at me like I was crazy. I then went to a psychiatrist with this and she was much more receptive. I am now switching to Effexor. Today is the first day so I am hoping that it will go well. I will keep you all posted on my progress but it is so nice to know that it was not just me.

Lynda (Nov 19, 2004) My husband was put on Paxil June 2004. He ran out and didn’t refill his prescription. I found out on the 3rd day and we got it refilled on the 4th day. He planned on starting back on it the following morning. It was too late, he flipped out that night and I found him the next morning – he hung himself September 30th.

IF YOU’RE NOT TAKING PAXIL, DON’T START. IF YOU’RE ON IT, BE EXTREMELY CAREFUL ABOUT GETTING OFF IT – DON’T GO COLD TURKEY.

I would like to help get this drug off the market. Please feel free to email me at LyndaLu99999@yahoo.com

Angie (Dec 4, 2004): This site is a god send. I started taking 20mg Seroxat approximately 3years ago. Before this I rarely drank and couldn’t tolerate alcohol, my friends would tease me about my pathetic intolerance to booze, and how I could get drunk after one can of lager. I was prescribed seroxat for depression, which I have suffered with for most of my life. I never took Ad’s before and didn’t self medicate with other drugs or alcohol. Following a very stressful time in my personal life and with work, my depression worsened, and after seeing my gp, I agreed to give them a go, following many consultations over previous years where I had refused. I found they worked instantly, and for the first six months I felt fantastic, then I began to crave alcohol, and found myself coming home from work, drinking until bedtime and going to work, next day without hangover. Weekends I just wanted to stay home and drink, and i drink until I physically could take no more, but mentally still wanted more. I didn’t want to see people, didn’t want to go out, I just wanted to be at home and drink. My life stopped, and whilst functioning at work, but desperate for the end of the day, to drink I felt empty and began to think about suicide all the time. Prior to taking seroxat, whilst feeling depressed, I did sometimes wonder about suicide but always had a strong feeling that I could never ever really do it, because of loved ones. However whilst on Seroxat I lost those reasons to live. I used to sit overwhelmed by compulsions to swallow tablets and take an overdose. Sometimes I could almost taste the tablets, and had to force myself to go to sleep, to get suicide out of my head. Over the past three years I have gone through cycles. I took the tablets, felt better, then would get increased suicidal thoughts and numbness and be drinking heavily. I would stop the tablets, feel severe withdrawal symptoms, dizziness, brain shudders, sweats, emotional outbursts, feel frightened start the tablets again, feel better for a bit then go down again, and repeat the cycle. I tried withdrawing from them slowly, as recommended by GP, but I still got the side effects. In despair, I have now decided to stop them instantly and suffer the withdrawls, and just hope they don’t last, because being depressed as i was before seroxat and the brief periods of feeling better when restarting them, after a couple of days being off them, is really not worth the feelings of wanting to end my life and becoming an alcoholic.

Jim (Dec 22, 2004): Hi, I have been on paxil on and off for the last 5 years or so. I have experienced all the same horrible side affects while trying to come off the drug as well. What I was wondering is if anyone has went out and drank too much in one night while taking the paxil. I overindulged in alcohol with my buddies which i know i shouldn’t have, and now it seems like the drug just stopped working. It has been a week now since my night out drinking, and i am as anxious as ever, dizzy, and feel like the drug just stopped working. Has anyone experienced anything like this? Thanks.

Kat (Jan 11, 2005): Reading others histories and tragedies has been eye opening. After being diagnosed by by GP, three years ago, I first started a small dosage of Paxil. My child was just two, and I had a situation where I should have seen a psychiatrist immediately. My husband and I went to a counselor instead and he recommended a family doctor. The Paxil helped me to sleep, stopped my anxiety attacks, nightmares, and angry outbursts, and thoughts of death. I felt happy and relaxed for a time. The drawbacks were a fuzzy numb headed feeling, electric zaps, and the overwhelming urge to smoke cigarettes, which I had only done occasionally before. Also I let the bills go unpaid without worrying about due dates. After being on the smallest dosage for awhile, I started to feel the anxious, dark feelings again, and my GP told me to try 20mgs. I was on and off, because of my conflicting feelings about taking medication. I then became pregnant and completely stopped for some months. Until my depression was back to the point where I could not function well, I read up on paxil and side effects on the baby in womb. I stayed on through the end of my pregnancy and through nursing my daughter until she was 11 months. I have recently been very low and not able to deal with day to day life. My doctor again prescribed taking Paxil, its been 7 months since I took myself off abruptly, experiencing headaches , vivid nightmares and nausea, but I think I will not return to the comfortable numbness. It has caused memory loss, and I feel like I have empathy, affection and other good emotions erased. I am going to try herbal medicine and try to get the old me back. May God bless the families of those that have lost their lives or been killed by mental illness and perhaps these medications.

Michael (Jan 14, 2005): I don’t know about all this reaction to Paxil. I’m Bipolar and been on it 5 years at about 40 mgs. I actually quit drinking. But I have had the electic Zap thing happen once and I didn’t connect it to the Paxil.

All I know is Paxil has allowed me to live a normal life that and mood stabilizing drugs. I’m glad its there because if you knew what my life was before six years ago, well I’ll tell you.

Jon (Feb 6, 2005): I knew I wasn’t the only one! I tried doing a search on Paxil and Alcohol and only found articles about how Paxil is used to treat Alcoholism. PLEASE! That’s like giving crackers to a thirsty person. Maybe it could work, if your drinking is due solely to depression, but my experience is that Paxil hits the “drink alcohol instead of water” button. Why is there so little written on this subject? Besides the alcohol, my short term memory is not reduced, its gone. Not to mention that I’m tired of women telling me how sore I make them (laugh if you want, it really sucks). Sure would be nice to have a good orgasm again without shredding her in the process.

I’m stable enough now that I’ve gotten a good job (thanks Paxil) but I don’t get my work done, get in trouble for forgetting assignments and not completing tasks (thanks Paxil). I guess it’s time to quit this poison pill and hope the zaps aren’t too bad. I’ve tried a couple times before cold turkey and couldn’t get past the nausea and brain shutdown.

Jessie 2/11 Pax-ills I, too, developed cravings for and high tolerance of alcohol when I began Paxil. And I was somehow able to wean myself from those cravings after a few years, remaining on Paxil.

Recently I quit Paxil cold turkey. I know, I know – bad idea. But I ‘d been on the stuff since 1994 and quit twice before. Once gradually, once abruptly. And I made the conscious decision to go abrupt this time (from 20mg to 0) to avoid the long drawn-out withdrawals in favor of the more extreme but sooner done symptoms.

I regret this decision. After 4-1/2 months I am still quite sick. And my withdrawal symptoms seem to ebb and flow with hormonal fluxes, so that Day 5-Day 14 is usually pretty good. Day 14 (ovulation) brings on burning in stomach, throat and mouth, some nausea, heightened sense of smell, blurry vision, restless sleep. That lasts through menstruation. Then 5 days off until it all starts up again.

Of course, I ‘m returning to a fairly severe chronic depression and though I loathe to return to the medicine that can produce these effects, I may have to simply to survive. When I think about trying a different SSRI or another of the newer anti-depressants, I tend to think that would just add a different set of potential longterm damages.

So its not just a physiological or psychological dependency, but a depressed person ’s reasoned choice to return to the evil you know, rather than the one you don ‘t.

Is there a good argument for trying a different medication. Paxil did after all work wonders – it only made me hypo-manic, killed my sex drive, and slight twitches but it did give me a chance to live life.

JY 2/17: Effexor / Paxil were key players in my cessation of alcohol / drug use. In other words — they helped me get sober! I ‘ve been taking paxil for about 2 years, and am more productive / happy / efficient / generally pleasant than ever before. Although, i ‘ve noticed that I am prone to extreme violent outbursts (mainly verbal) which is totally not my style, and it even seems that my anxiety is worse than ever. But my depression is all gravy, which is honestly the only thing that matters to me.

Yeah, there ’s some weird side effects. I tour a lot out of the country, DJing in clubs, and after a late night, i often feel hungover (even though i don ‘t drink alcohol). I also get giant red spots on my neck and face during interpersonal interaction (especially phone calls).

Sooooo, switched to Effexor XR today, cold-turkey. Took it a few years ago and it worked like a charm. we ‘ll see what happens.

Please do not discount the fact that anti-depressants improve and even SAVE peoples ‘ lives. I for one am not sure i ‘d be alive today if it weren ‘t for them.

Also don ‘t feel guilty about taking them. I know sometimes it plays with your head, realizing that you ‘re taking a pill everyday. Sometimes society tells you that ’s weird, or not okay. But if you ‘re taking an anti-depressant, there ’s probably a good reason for that. And for some of us, we need to come to terms with the fact that we have a chemical imbalance and might need to take medication for that for the rest of our lives. And that ’s okay. If the benefits outweigh the drawbacks, it ’s probably good that you are taking it.

Stu 2/20 i also did a search looking for links about alcohol problems and paxil. i only know of three people including myself who have taken this drug, all three have had their lives destroyed due to the above mentioned alcohol cravings/tolerance. i came off cold turkey in 2001 and i,m lucky to be here. i tried reducing the dose under doctors orders but it was to painful, i wish i could have coped with the pain and done it slowly but i needed to break the addiction fast.

ArkansasChick 3/10 Being victim to the legal poison Paxil my symptoms are the same as others I’ve read about with the exception of feelings of being poisoned and losing my hair. That’s right! I looked like the crypt keeper on TV. I wonder how many years paxil can effect people. Surely the side effects aren’t forever.

Eric 3/11 Paxil and wanting to drink I took paxil for almost 2 years. In that time i became someone i didn’t even know anymore. I started drinking and even tried other drugs which i never would have even thought about untill the Paxil opened up my insides and made me aggressive and care free. I was starting to get into fights and i even got in trouble with the law fighting with them which unfortunately has cost me 16 thousand dollars. All i can say is…i was never violent or care free until i started Paxil. It was like the Paxil made me want to drink, something i hated to be around. I have been Paxil free now for 6 months and i am back to my old self. No more drinking and no more getting into trouble.

Jay 3/11: Thank goodness for all the side effects my wife and son experienced on these hellish SSRI antidepressants. After my son’s arrest after experiencing a Effexor induced psychotic break and also while in Paxil withdrawal, we found out that their depression and anxiety were simply caused by Hypoglycemia. Thank goodness for sites like http://www.alternativementalhealth.com. No more drugs of any kind in our lives. It’s all natural from here.

Pitufo 3/25: Paxil has increased my drinking as well… No Hangovers!!! It’s f@#$’d up! Now I can drink every night, ignoring my alcoholism because i have no hangover. I’ve been doing it for about 10 months and now, because of personal social problems, I am exhibiting a lot of subtle anger (towards myself and others) and it all comes out when I drink. Which is every night because I can now without the repercussions of the hangover and associated symptoms…. I would mention suicidal thoughts but that only happens when I’m really angry (livid) and besides that I am aware that it is just my current living situation…. But those thoughts (and actions) are definitely new.

Shellie 4/26: OK…I happen to LOVE Paxil. I have had social anxiety disorder for most of my life. I can honestly say that I never had a happy life until after taking the medication. I could think clearer. I was just a happier person in general. My life started to make sense in more ways that I could possibly tell you. What I believe is happening…is doctors..medical doctors..are prescribing Paxil, and do not have any knowledge of the mental disorder they are prescribing it for, or the side effects of the medications. So I believe the people who are having these problems that are so “horrible” are because they should have never taken the medication to begin with. They didn’t need it. Paxil is for people with extreme mental disorders like myself.

Dee 5/15: I started taking Paxil CR for Social Anxiety about 1 year ago. I had previously tried some other anti-anxiety and anti-depressants but my new doctor recommended Paxil CR. I have never been much or a drinker, and I have never had alcohol cravings. In fact I never tried alcohol on this med. As for me, I feel that Paxil does seem to work in treating some aspects of my social anxiety but I also am more aware of my anxiety and I don’t know if it is because I am aware of it or if I am experiencing more (whether or not Paxil related). However, I have tried to stop taking the med because I’ve felt at times a lack of motivation and loss of memory or perhaps just the ability to focus. I am 27 yrs old and I have been studying for fairly technical financial certifications and have been having trouble having the motivation or the energy to study. I’ve not had this problem before.

Julie 6/16: Wow. It isn’t “just me”. I am in the process of getting off Paxil. I had no idea that it would be so hard.

I, too, craved alcohol while taking Paxil. I would have a glass of wine and then I would not stop until the bottle was gone. I usually could care less about drinking.

And, instead of being “warm & fuzzy”, I became a violent, angry, out of control person. I would do horrible things and not remember the next morning. My husband accused me of being an alcoholic and having a personality disorder. We almost divorced and are still feeling the repercussions. I got “pushy” with my psychiatrist to switch me off of Paxil to another SSRI. Now, after doing searches on “Paxil Withdrawal”, I can understand why he was so hesitant.

My medical Dr. informed me that she does not like Paxil as the “crash” getting off it is so severe.

Where is the FDA? Peoples lives are being torn apart, ended, ruined, destroyed by this drug.

Amber 6/20: I have been on Paxil for about three years and then slowly weaned myself off of it. The withdrawal was hard but having your doctor work with you and understand the symptoms can help.I stayed Paxil free until My panic attacks started to come back last fall. My doctor asked me if I wanted to go back on Paxil and now I am doing great. I am not angry anymore and I can go anywhere without having an anxiety attack. As for drinking, I just don’t do it anymore. Drinking is said to decrease the effects of Paxil, which would be blocking the same reason I’m on it.

Jean 6/29: Been off Seroxat nearly 3 weeks now and still having symptoms dizziness, not eating etc. does it ever end

Sherrie H. 7/10: I have been on Paxil for about 8 or 9 years. i sought it out for depression. i thought it was helping me but over the years i have slipped back into the depression PLUS i used to be a shy, nice, quiet, normal person. the Paxil has made me a loud, obnoxious, mean, irritable person. i drink alcohol about once or twice a year. i thought i was having fun and seemed to have NO FEARS when drinking on Paxil. i can drink all night long and never want the party to end. before Paxil i was not like that. it has caused problems with the people i have drank with and the next day they tell me i have done and said violent things. i was mortified that THEY thought i acted like that! i remember the entire night and speaking to my family members. i remember getting mad at them BUT i do not remember the MEAN, VIOLENT, things they say i did. i have lost several family members respect and love because of Paxil. it has effected my normal every day life to the point that i feel like i am going crazy. i have had thoughts of severe anger at every thing around me to the point that i have been to the doctor having all kinds of blood work drawn up because i thought my thyroid meds where out of whack but i stumbled onto some of the many sites on the internet like this one and now know what and WHY i am so out of control and the many effects paxil has had on people just like me. i take 30 mg of Paxil and today i am going to start weaning myself off of this horrible mind altering drug. i have been taking it soooo long that i am not sure how long it will take to get out of my system. i know i can not change the things i have said and done that have hurt the people closest to me but at least i am finding out these horrible stories of anger and rage that had deadly consequences BEFORE i have gone that far. wish me luck and power on my struggle to become Paxil free and anger free again.

Skeeweeaka 7/15: I believe that the long-term affects of antidepressants are really not fully known. I also believe that our psychiatrists understate the side affects and how they drastically change the context of our lives as we are trying to fight off depression and anxiety. For me, it has meant weight gain, loss of libido, increased anxiety, social isolation, psychotic episodes, paranoia, etc. All of these hings have increased as a result of the drugs, in addition to seizures and the fact that they are only controlled with meds of which I do not want to take…

New Life 7/16: Paxil gave me my life back. I had severe panic attacks throughout my teen years but those were blamed on “being a teenager”. After my father died (whom I performed CPR on and had to inform the rest of my family that he had passed) I just shut everything out. I wasn’t sleeping for days. I would drive from point A to point B and not even remember doing it. I was beginning to lose days at a time. When I finally did sleep and could not get out the bed because I just did not want to deal, I knew I needed help. They put me on Paxil. I did so well. I did put on some weight, but I would rather be chubby than crazy! Going off of Paxil, I have tried 3 times and I was worse than before I went on it! I would lose my balance, fall down stairs, not sleep, not be able to drive, and go back on it. My doctor has given me the option to switch to Effexor, but I am afraid to go off of the Paxil. I even had to take Paxil during my pregnancy because my doctor said that electro-shock therapy would be my only recourse. When I told my OB about the ES therapy, she freaked! She said that Paxil is the only drug for depression that she gives her patients and then promptly called my doctor “a nutty quack”. As for the alcohol, one drink and I’m loopy. My husband calls me the “cheap date”. Anyway, I would love to hear from anyone who has taken both Paxil and Effexor at the same time in order to go from one to the other. I am hoping that I may get the courage to switch.

Bobby 7/17: Regarding increased alcohol consumption – I recently read this in the book “Under the Influence” (Bantam Books, 1983, page 38):

“Preference for alcohol is undoubtedly regulated by complicated activities in the brain. In a 1968 experiment, rats dramatically reduced or completely stopped drinking alcohol when given a chemical substance which depleted the brain’s supply of serotonin. (R.D. Myers and W.L. Veale,”Alcohol Preference in the Rat: Reduction Following Depletion of Brain Serotonin”, Science, Vol.160 (1968), pp.1469-71.)Serotonon, a brain amine resonsible for relaying brain messages from one brain cell to another, appears to increase the animal’s preference for alcohol. The brains of alcohol seeking mice and rats, for example, contain higher levels of serotonin than the brains of alcohol-avoiding animals. Further, drinking serotonin increases serotonin concentrations in the brains of the animals that show a preference for alcohol but not in those that avoid it.”

Lana 7/20: Yet another one – i thought i was mad. i actually have been a binge drinker for many years but could not believe the effect Paxil had on my drinking. i was a weekend drinker and have become an every day heavy drinker. and no hangover. i have tried taking up other things, but the fatigue that Paxil induces does make that difficult. I’m quite a proficient knitter now and thoroughly enjoy it. despite the knitting. i too have lost my driving license. I’ve only been on the drug for about 8 months.

I’m saving all your comments for my partner who I’m sure doesn’t believe what I have for some time, that the drug has had this effect. i’ve been much too embarrassed to say to my doctor that I’ve increased drinking – cos of the warning on the packet. but I will now – i think that there needs to be more information about this – there may only be a few of us who suffer this bizarre side effect.

We may not win a law suit and glaxo whatsit may not take responsibility, but i am convinced now that it really just one more thing that needs to be recognised as a side effect and written into the warnings.

MK 7/20: I have been on Paxil for about 2 years. Approximately a year ago, I started drinking heavily. Prior to this, I only drank once in awhile and never really enjoyed it. FOr the past year, I have been drinking almost every night. Luckily it has not destroyed my life and I am trying to get a hold on things. Last month I decided to try and quit Paxil as I didn’t feel that is was needed. When I am not on Paxil, I don’t get depressed. I am tapering myself off. I have used alcohol to help taper myself off (as sad as that sounds). Again, prior to paxil, I was a light drinker. When I did get drunk, I would get very drunk off of little alcohol. With Paxil it seems I can drink like crazy. 15 or sixteen drinks can’t put me down. Then, as I have been tapering off the Paxil, I had an experience where just two glasses of wine get me wasted to the point of almost passing out. The cravings for alcohol have suddenly subsided. Regardless of what an attorney would say about this, I believe a correlation exists for me and I would agree that the volume of postings and the amount of people that found this post by searching for “alcohol and Paxil” is pretty interesting.

Debbie 7/23: My nephew had the same thing happen to him as with PRP, except he was convicted and now is doing 40 yrs. for 1st Degree Attempted Murder.

Anthony 8/6: With regard to the various comments about Paxil and alcohol. Believe me, it’s true. Perhaps not fore everyone but I have been on Paxil for three years and I’ve had a problem with drinking, drugs and cravings the whole time. I heard whispers about there being a problem with this a few years ago but I prefer to take responsibility for my own issues. However I have seen two other people in my life go completely off the rails with substance abuse within a few months of starting on Paxil.. coincidence, perhaps. However I will leave you with this thought, I am currently weaning myself off Paxil through very gradual reduction. Bad dreams, bad moods and depression are back.. but guess what? I don’t feel like drinking.

MR 9/12: Son was on it, he tried suicide three times. Last time was a gun to his head. He was 13. He had vivid dreams, nighmares and what he reffered to as daymares (having nightmares while you are awake). He was put on Paxil because he had been bullied in school for 5 years. The school wanted him treated not rather than deal with their problems. He was not suicidal just lonly, and these drugs almost took him from us. He took to cutting himself, just to feel something, his doctor upped his dose. This was all before the FDA warnings. Stll my son was prosecuted on a gun charge, at the time he was just 5′ and 199lb. He was in one hospital center who took him off all meds, and they found out that in a safe enviroment he was a well balanced child, no need for medication, and no suicide ideation. He has been off these drugs fo 2 years now. He still has flashbacks, but deals with them with them explaining “it is just his brain rewiring itself”. He is a happy average teenage boy. He has been to the FDA hearings, and has protested against the Drug companies and FDA. He will not sit back and let someone else be harmed by these drugs.

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