Dr Chuck Nemeroff, CeNeRx and his amazing, missing disclosure…

CL Pysch has a great story:

Seems Chuck is a consultant for 18 drug companies and a speaker for four. His list of disclosures from a recent piece of CME (continuing medical education) in the USA reads like this:

AstraZeneca Pharmaceuticals, LP, Bristol-Myers Squibb Company, Forest Laboratories, Janssen Pharmaceutica, National Institute for Mental Health, Pfizer Inc, Wyeth-Ayerst Laboratories, Consultant: Abbott Laboratories, Acadia Pharmaceuticals, Bristol-Myers Squibb Company, Concept Pharmaceuticals, Ltd, Cypress Bioscience, Inc, Cyberonics, Inc, Eli Lilly and Company, Entrepreneur Fund Inc, Forest Laboratories, GlaxoSmithKline, H. Lundbeck A/S, Ingenix i3 DLN, Janssen Pharmaceutica, Otsuka America Pharmaceutical, Inc, Pfizer Inc, Quintiles Transnational Corporation, UCB Pharma, Wyeth-Ayerst Laboratories; Speaker: Abbott Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc.; Stockholder—Acadia Pharmaceuticals; Corcept Therapeutics, Inc; Cypress Biosciences; NovaDel Pharma Inc.; Board of Directors: American Psychiatric Institute for Research and Education, NovaDel Pharma Inc, National Foundation for Mental Health.

The CME piece in question was comparing MAOIs with SSRIs and Chuck wrote “Certainly other data and my own experience would suggest that MAOIs are superior to SSRIs and TCAs [for atypical depression]”.

He also wrote “A new transdermal system is currently available that enables the MAOI to avoid first-pass metabolism by bypassing the gut, thereby reducing the chance of hypertensive reactions caused by tyramine.”

And the Missing Disclosure?

Remember how the above CME was all about pushing a newer, safer MAOI drug for depression? Well, it just so happens that Nemeroff is the co-chair of the Scientific Advisory Board for CeNeRx, a company that is developing a (you guessed it) newer, safer MAOI drug for depression! Note that Nemeroff did not mention his position with CeNeRx in his disclosure for the Medscape CME activity. And here’s what the CEO of CeNeRx had to say about the MAOI they are testing:

“In contrast to other MAO inhibitors, our third generation RIMA series is designed to bind selectively and reversibly, with the goal of significantly reducing the cardiovascular risks and other side effects typically associated with the MAOI class. These safety results, along with the high plasma levels and favorable pharmacokinetics demonstrated in the study, support advancing Tyrima into a multiple dose safety study in late spring.”

So let me get this right. Chuck talks up a new third generation MAOI in a CME activity, yet does not disclose that he is being paid by the company which also manufactures that third generation MAOI

Nice work Chuck.

Read the whole sordid story over at CL Pysch’s blog – now!…

Harrington Investments Divests From GlaxoSmithKline

August 29, 2007

Contact: Jack Ucciferri

(707) 257-7923 Fax

(707) 252-6166 Voice

www.harringtoninvestments.com

Harrington Investments Divests From GlaxoSmithKline

Cites Litany of Concerns

Napa, CA – Harrington Investments, Inc. (HII), a socially responsible investment (SRI) advisory firm, announced today that it has divested from GlaxoSmithKline (GSK) stock.

“In accordance with our long term investment management style, we would prefer to remain invested in GSK,” said John Harrington, President and CEO of Harrington Investments. “However, we have a fiduciary duty to our clients that includes a comprehensive review of a corporation’s overall operations and reputation.”

In a letter to GlaxoSmithKline CEO, Jean-Pierre Garnier, Harrington listed six points of concern with the company, including investigations for shady business dealings with Saddam Hussein, improper marketing of anti-depressants, and tax avoidance.

The letter also cited GSK’s inability to address the concerns of animal rights activists and its resistance to providing affordable AIDS drugs to developing countries.

The list concludes: “On a lighter note, we are bemused that GSK – one of the largest drug makers in the world – was recently ‘busted’ by two 14-year-old schoolgirls for wildly exaggerating the quantity of vitamin C present in a popular children’s fruit drink! Unfortunately, however, this action on the part of GSK continues to undermine your company’s reputation and your management’s credibility.”

Like many SRI firms, HII proactively avoids, or ‘screens out,’ stocks of corporations with significant negative environmental, social, and/or corporate governance (ESG) issues. Once it decides to purchase shares in a company, HII generally tries to work with corporate management to improve ESG performance.

HII’s divestiture of GSK stock is a reaction to corporate management’s consistent failure to address important investor fiduciary concerns.

#######

Jack Ucciferri
Research and Advocacy Director (RAD)
Harrington Investments, Inc.

ph. 707.252.6166
fax 707.257.7923

jack@harringtoninvestments.com

Challenges Persist for JP Garnier at Glaxo

A string of high-profile setbacks isn’t what Jean-Pierre Garnier envisioned as he enters the home stretch as CEO of GlaxoSmithKline, writes Robert Steyer at TheStreet.com

Back in 2006, he agreed to delay his retirement until May 2008, instead of October 2007, so he could shepherd the launch of new drugs with alluring revenue prospects. Instead, Garnier is spending much of his time defending the diabetes drug Avandia, coping with regulatory and scientific delays for two touted compounds and supervising a giant stock repurchase due to Glaxo’s slumbering shares.

“Diversity is Glaxo’s biggest strength,” says Heather Brilliant of the independent research firm Morningstar. “Clearly, Avandia will be an overhang for awhile. But Glaxo can withstand the bumps that affect other companies.” However, others say the new and experimental drugs won’t offset revenue surrendered from products that have lost patent protection or will lose exclusivity in the next few years. If Glaxo is too big to fail, it’s also too big to grow significantly without developing more mega-medications.

Glaxo suffers from “deteriorating earnings power,” says Alexandra Hauber, of Bear Stearns, in a recent report illustrating the bear case for Glaxo. Her underperform rating is based partly on the belief that “the combined sales potential of [R&D] pipeline assets looks insufficient to sustain GlaxoSmithKline’s earnings into the next decade.”

Hauber’s assessment came before an FDA advisory panel in late July recommended more restrictions for Avandia because they say it raises heart-attack risks. Afterwards she said Avandia’s prescription volume was “unlikely” to recover. Hauber’s firm has had a noninvestment banking relationship.

For the 12 months ended Aug. 15, Glaxo’s stock was down 10.4% while the Amex Pharmaceutical Index of mostly giant drugmakers was down 4.2%. Glaxo tried to prop up the stock last month with a big stock buyback, saying it will expand an original repurchase plan from $8.8 billion to $24.6 billion over the next two years. That may have temporarily mollified equity investors, but Moody’s Investors Service dropped Glaxo two notches from the Aa2 high-grade level to A1 upper-medium-grade.

Avandia remains Glaxo’s biggest headache as well as its second-biggest seller. Some medical research says Avandia raises the risk of heart attacks compared to other diabetes pills, a claim that Glaxo disputes. A recent recommendation by advisers to the FDA portends more restrictions and lower sales for the drug whose U.S. sales fell 31% in the second quarter and whose worldwide sales dropped 22%.

The FDA doesn’t always agree with its advisors, but it usually does so. The advisors voted 22-1 to keep Avandia on the market, but they also agreed by a 20-3 vote that Avandia has a higher risk of heart attack than other pills that control blood sugar.

Last week, the FDA said Avandia’s label will include the agency’s strongest alert for the risk of heart failure — the impaired pumping ability of the heart. Avandia’s label has carried a less urgent warning about heart failure, and the FDA is still reviewing the research on heart-attack risk.

Speaking of headaches, Glaxo and its partner Pozen (POZN – Cramer’s Take – Stockpickr) were recently hit with another delay for their migraine treatment Trexima. The FDA granted conditional approval in early August, but one condition is more testing, which could take several months. The original application was filed two years ago, and the FDA issued its first conditional approval in June 2006. “We think the drug has a decent chance of being approved,” says a recent note by the independent research publication BioMedTracker, which analyzes drug and biotechnology prospects.

Trexima represents a standard Big Pharma generic-competition defense — developing a close relative of a brand-name drug. Trexima combines the generic pain reliever naproxen with Glaxo’s patented Imitrex.
For the first half of 2007, Imitrex produced $656 million. U.S. sales rose 11%, but sales in Europe and other foreign markets were down. U.S. generic competition will start in February 2009. Glaxo wants to secure early FDA approval so it has more time to persuade doctors and patients that newer is better.

Trexima isn’t the only problematic partnered product. Another is Entereg, developed by Adolor, for treating constipation and bowel disorders in patients who take powerful drugs for chronic, noncancer pain.

Entereg has suffered a host of delays. In April, Glaxo and Adolor said unusual results in a late-stage clinical trial caused them to suspend several other studies. Patients taking Entereg had a higher-than-expected rate of cardiovascular problems, as well as benign and malignant tumors. The companies are reviewing the research, and they are preparing a response to the FDA’s questions about another use for Entereg.

In November, the FDA granted conditional approval to the product for treating post-operative ileus, or constipation and abdominal pain caused by high-strength painkillers taken by people recovering from surgery. The FDA wants more data about possible cardiovascular side effects, and the companies plan to file their response before Sept. 30.

November’s delay wasn’t the first for Entereg. The companies received conditional clearance in July 2005 with the agency asking for more efficacy data. Clinical trial results have played havoc with Adolor’s stock over the years.
And even when a partnered product reaches the market, the path to higher revenue isn’t always smooth.

Coreg CR, a controlled-release version of the blood-pressure/heart failure drug Coreg, is off to a weak start following a first-quarter launch. Coreg CR had $20 million in sales in the second quarter vs. Coreg’s $400 million.
Flamel Technologies (FLML – Cramer’s Take – Stockpickr)developed Coreg CR, but Morningstar and other observers say the drug has been slow out of the gate primarily due to Glaxo’s sales force spending so much time defending Avandia.

Lisa Blakemore-Brown, The British Psychological Society, Dr Rita Pal and the GMC – 2

Still more on this sorry tale of the GMC and the way it does business.

My first post on the story can be found here.

Now, I’d suggest you all go here to read the latest from Dr Aubrey Blumsohn at Scientific Misconduct.

The GMC (like the MHRA) has remained silent about the most serious and damaging integrity failures in medicine. This includes several cases of misrepresentation of commercially motivated pharmaceutical research (by doctors) which has led to untold suffering by patients. To facilitate the integrity lapses, all the GMC had to do was to do nothing – and they have done nothing with unparalleled skill.

Drug companies manipulate legal system to deny justice to patients

New York Times 21 August 2007

Merck’s Vioxx Defence Strategy Prevents Plaintiffs From Getting Compensation: The case of Vioxx litigations demonstrates that consumers of inadequately tested FDA-approved medicines that prove lethal, are no better off than in the pre-FDA snake-oil era.

The New York Times reports that despite Merck’s withdrawal of Vioxx from the market due to its causing cardiovascular damage, Merck’s legal defense strategy is working: The strategy’s successes, from the view of Merck and its shareholders, are clear:

“In fact, none of the 45,000 people who have sued Merck, contending that they or their loved ones suffered heart attacks or strokes after taking Vioxx, have received payments from the company. The lawsuits continue, for now in a state of legal limbo, with little prospect of resolution. In combating the litigation, Merck has made an aggressive, and so far successful, bet that forcing plaintiffs to trial will reduce the number of Vioxx lawsuits and, ultimately, its liability. Promising to contest every case, Merck has spent more than $1 billion over the last three years in legal fees. It has refused, at least publicly, to consider even the possibility of an overall settlement to resolve all the lawsuits at once.”

Plaintiff’s lawyers accuse Merck of manipulating the legal system “to deprive justice to tens of thousands of people whose cases can never be heard.”

Glaxo and all the the other drug companies take exactly the same action – they’re not interested in protecting patients, all they’re interested in is their profits.

If drug companies ever do have to make payouts, then they will make the payout conditional upon signing a gagging order – to keep the truth hidden – they buy our silence.

JP Garnier and his New Flu Vaccine plans: Just Another ‘Stupid Investment?’

You’ve got to wonder about JP and his stewardship of Glaxo. Just when he must have been happy to tie up some bird flu vaccine deals, we learn things may not be so straightforward. This from Ed Silverman at Pharmalot:

Have Glaxo and Novartis stumbled yet again? That’s the question raised in a look at Protein Sciences, a much smaller company using a DNA technology to develop flu vaccines that may prove faster than the methods being used by its much bigger rivals, Bloomberg News reports.

Losing the flu-shot race may be the latest in a series of setbacks for both drugmakers, which are building plants that are part of a $1 billion US initiative to produce millions of inoculations within six months of an outbreak of a deadly flu. But Protein Sciences, with just 40 employees, is close to winning approval for a method that would cut the time at least in half.

Novartis is investing $600 million to build a cell-based flu-shot plant in North Carolina, and has won a $221 million US government grant for clinical trials. And Glaxo, which is getting $275 million in US funding, is building a Pennsvlvania factory in a facility acquired from Wyeth for an undisclosed sum. Both are growing influenza virus in animal cells as an advance over the decades-old technique of making flu shots using chicken eggs.

But cell culture “is an amazingly stupid investment to make for the future,” argues Manon Cox, Protein Sciences’ chief operating officers. “It’s as if we’re still living 100 years ago and recombinant DNA was never developed.”

Apotex and Toronto University

This story just seen on the Scientific Misconduct blog – a must read!

Here’s the situation:

You are Robert Prichard, the President of a University. The University of Toronto to be specific. There is chaos all around you caused by the attempt by Dr Olivieri to publish what she has found in a drug trial involving a big commercial company. Apotex to be specific. One academic, Gideon Koren is sending anonymous threatening correspondence to several other academics. You are caught in the middle of all of this.

You receive a letter. You suddenly realise who it is from. It’s Dr Bernard C Sherman PhD P. Eng (CEO of Apotex Inc)!

It begins: “As you know, Apotex has committed to donate to the University of Toronto $20 million for the new Medical Sciences Building, and Is close to finalizing an agreement to increase the donation to $55 million, which would also encompass a new building for the Faculty of Pharmacy and other projects. I am writing to advise you that Apotex is now confronted with an Impending force majeure, which, if not averted, will likely compel cancellation of our entire commitment to the University.”

Read on here – you won’t believe it.

I’m not sure what you would call the Apotex letter – maybe a suggestion – maybe a request – maybe lobbying – maybe blackmail – maybe a threat – maybe a command?

I just can’t make make up my mind – I’ll leave that to you…

Lisa Blakemore-Brown, The British Psychological Society, Dr Rita Pal and the GMC

Sorry to be late with this story, but I’m back in the chair now after spending a couple of weeks in Northumberland on the north east coast of England (which is where I come from – but even I never get used to the weather that we are treated to from time to time!)

I’m sure regular readers of pharma blogs may well know the story of Dr Lisa Blakemore-Brown – I’ve written about her case here, here and here. So has another blogger – a British doctor named Rita Pal who writes for the NHS Exposed blog and she linked to a document on the Furious Seasons website (as I did) which is transcript of Blakemore-Brown’s British Psychological Society hearing. The problem is that the BPS wanted to keep the transcript private (Blakemore-Brown did not).

It seems that Dr Pal has lost her job over this and now the General Medical Council, which regulates doctors in the UK, is investigating her.

This one is getting complicated so I suggest you go over to Furious Seasons now, where you’ll find a great article explaining everything.

[I wonder who you can complain to if you’re not happy with the GMC itself?]

Seroxat prescribing infomation updated in the UK

Well, it had to happen… Glaxo have updated the prescribing information for Seroxat.

Not the PIL that is supplied with the drug, but the detailed prescribing information that can be found here. My thanks to Truthman30 for alerting me to this.

We will have to wait to see if the PIL changes at all (and when) – but surely it must change to reflect this major revision to the prescribing information (but it’s still too little too late).

One question for Glaxo – why are tablets not available in 5mg and 2.5mg strengths – to take this simple step would help all the patients who suffer from withdrawal symptoms when trying to stop taking the drug.

Two sections of the revised document are of particular interest – Special warnings and precautions for use and Undesirable effects – read them carefully:

4.4 Special warnings and precautions for use
Treatment with paroxetine should be initiated cautiously two weeks after terminating treatment with an irreversible MAOI or 24 hours after terminating treatment with a reversible MAO inhibitor. Dosage of paroxetine should be increased gradually until an optimal response is reached (see section 4.3 Contraindications and section 4.5 Interactions with other medicinal products and other forms of interaction).

Use in Children and adolescents under 18 years of age.
Paroxetine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide related behaviours (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If based on clinical needs, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

Suicide/suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which paroxetine is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta analysis of placebo controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old (see also section 5.1).

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Akathisia/psychomotor restlessness
The use of paroxetine has been associated with the development of akathisia, which is characterized by an inner sense of restlessness and psychomotor agitation such as an inability to sit or stand still usually associated with subjective distress. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.

Serotonin syndrome/neuroleptic malignant syndrome
On rare occasions development of a serotonin syndrome or neuroleptic malignant syndrome-like events may occur in association with treatment of paroxetine, particularly when given in combination with other serotonergic and/or neuroleptic drugs. As these syndromes may result in potentially life-threatening conditions, treatment with paroxetine should be discontinued if such events (characterised by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes including confusion, irritability, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated. Paroxetine should not be used in combination with serotonin-precursors (such as L-tryptophan, oxitriptan) due to the risk of serotonergic syndrome.

Mania
As with all antidepressants, paroxetine should be used with caution in patients with a history of mania. Paroxetine should be discontinued in any patient entering a manic phase.

Renal/hepatic impairment
Caution is recommended in patients with severe renal impairment or in those with hepatic impairment. (see section 4.2 Posology and method of administration)

Diabetes
In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Epilepsy
As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.

Seizures
Overall the incidence of seizures is less than 0.1% in patients treated with paroxetine. The drug should be discontinued in any patient who develops seizures.

ECT
There is little clinical experience of the concurrent administration of paroxetine with ECT.

Glaucoma
As with other SSRI’s, paroxetine infrequently causes mydriasis and should be used with caution in patients with narrow angle glaucoma or history of glaucoma.

Cardiac conditions
The usual precautions should be observed in patients with cardiac conditions.

Hyponatraemia
Hyponatraemia has been reported rarely, predominantly in the elderly. Caution should also be exercised in those patients at risk of hyponatraemia e.g. from concomitant medications and cirrhosis. The hyponatraemia generally reverses on discontinuation of paroxetine.

Haemorrhage
There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura with SSRIs. Other haemorrhagic manifestations e.g. gastrointestinal haemorrhage have been reported. Elderly patients may be at an increased risk.

Caution is advised in patients taking SSRI’s concomitantly with oral anticoagulants, drugs known to affect platelet function or other drugs that may increase risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most TCA’s, acetylsalicylic acid, NSAID’s, COX-2 inhibitors) as well as in patients with a history of bleeding disorders or conditions which may predispose to bleeding.

Drugs affecting gastric pH
In patients receiving oral suspension, the paroxetine plasma concentration may be influenced by gastric pH. In vitro data have shown that an acidic environment is required for release of the active drug from the suspension, hence absorption may be reduced in patients with a high gastric pH or achlorhydria, such as after the use of certain drugs (antacid drugs, histamine H2-receptor antagonists, proton pump inhibitors), in certain disease states (e.g. atrophic gastritis, pernicious anemia, chronic Helicobacter pylori infection), and after surgery (vagotomy, gastrectomy). The pH dependency should be taken into account when changing paroxetine formulation (e.g. the plasma paroxetine concentration may decrease after changing from tablet to oral suspension in patients with a high gastric pH). Caution is therefore recommended in patients when initiating or ending treatment with drugs increasing gastric pH. Dose adjustments may be necessary in such situations.

Withdrawal symptoms seen on discontinuation of paroxetine treatment
Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.8 Undesirable effects). In clinical trials adverse events seen on treatment discontinuation occurred in 30% of patients treated with paroxetine compared to 20% of patients treated with placebo. The occurrence of withdrawal symptoms is not the same as the drug being addictive or dependence producing.

The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction.

Dizziness, sensory disturbances (including paraesthesia,electric shock sensations and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances have been reported. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that paroxetine should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient’s needs (see “Withdrawal Symptoms Seen on Discontinuation of Paroxetine”, Section 4.2 Posology and method of administration).

4.8 Undesirable effects
Some of the adverse drug reactions listed below may decrease in intensity and frequency with continued treatment and do not generally lead to cessation of therapy.Adverse drug reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (1/10), common (1/100, <1/10), uncommon (1/1,000, <1/100), rare (1/10,000, <1/1,000), very rare (<1/10,000), including isolated reports.

Blood and lymphatic system disorders
Uncommon: abnormal bleeding, predominantly of the skin and mucous membranes (mostly ecchymosis).
Very rare: thrombocytopenia.
Immune system disorders
Very rare: allergic reactions (including urticaria and angioedema).

Endocrine disorders
Very rare: syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
Metabolism & nutrition disorders
Common: increases in cholesterol levels, decreased appetite
Rare: hyponatraemia.
Hyponatraemia has been reported predominantly in elderly patients and is sometimes due to syndrome of inappropriate anti-diuretic hormone secretion (SIADH).

Psychiatric disorders

Common: somnolence, insomnia, agitation.
Uncommon: confusion, hallucinations
Rare: manic reactions, anxiety, depersonalisation, panic attacks, akathisia (see section 4.4 Special Warnings and Special Precautions for use).
These symptoms may also be due to the underlying disease.

Nervous system disorders
Common: dizziness, tremor.
Uncommon: extrapyramidal disorders.
Rare: convulsions.
Very rare: serotonin syndrome (symptoms may include agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, shivering, tachycardia and tremor).
Reports of extrapyramidal disorder including oro-facial dystonia have been received in patients sometimes with underlying movement disorders or who were using neuroleptic medication.

Eye disorders
Common: blurred vision.
Very rare: acute glaucoma.
Ear and labyrinth disorders
Frequency not known: tinnitus.

Cardiac disorders
Uncommon: sinus tachycardia.
Rare: bradycardia.
Vascular disorders
Uncommon: transient increases or decreases in blood pressure.
Transient increases or decreases of blood pressure have been reported following treatment with paroxetine, usually in patients with pre-existing hypertension or anxiety.

Respiratory, thoracic and mediastinal disorders
Common: yawning.

Gastrointestinal disorders
Very common: nausea.
Common: constipation, diarrhoea, dry mouth.
Very rare: gastrointestinal bleeding.

Hepato-biliary disorders
Rare: elevation of hepatic enzymes.
Very rare: hepatic events (such as hepatitis, sometimes associated with jaundice and/or liver failure).
Elevation of hepatic enzymes have been reported. Post-marketing reports of hepatic events (such as hepatitis, sometimes associated with jaundice and/or liver failure) have also been received very rarely. Discontinuation of paroxetine should be considered if there is prolonged elevation of liver function test results.

Skin & subcutaneous tissue disorders
Common: sweating.
Uncommon: skin rashes, pruritus.
Very rare: photosensitivity reactions.

Renal & urinary disorders
Uncommon: urinary retention, urinary incontinence.

Reproductive system & breast disorders
Very common: sexual dysfunction
Rare: hyperprolactinaemia/galactorrhoea.
Very rare: priapism.

Musculoskeletal disorders
Rare: arthralgia, myalgia.

General disorders and administration site conditions
Common: asthenia, body weight gain.
Very rare: peripheral oedema.

WITHDRAWAL SYMPTOMS SEEN ON DISCONTINUATION OF PAROXETINE TREATMENT
Common: Dizziness, sensory disturbances, sleep disturbances, anxiety, headache.
Uncommon: Agitation, nausea, tremor, confusion, sweating, emotional instability, visual disturbances, palpitations, diarrhoea, irritability.
Discontinuation of paroxetine (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia,electric shock sensations and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, confusion,sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances have been reported.

Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when paroxetine treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 Posology and Method of Administration and, 4.4 Special warnings and Special precautions for use).

Adverse events from paediatric clinical trials
In short term (up to 10-12 weeks) clinical trials in children and adolescents, the following adverse events were observed in paroxetine treated patients at a frequency of at least 2% of patients and occurred at a rate at least twice that of placebo were: increased suicidal related behaviours (including suicide attempts and suicidal thoughts), self-harm behaviours and increased hostility. Suicidal thoughts and suicide attempts were mainly observed in clinical trials of adolescents with Major Depressive Disorder. Increased hostility occurred particularly in children with obsessive compulsive disorder, and especially in younger children less than 12 years of age. Additional events that were more often seen in the paroxetine compared to placebo group were: decreased appetite, tremor, sweating, hyperkinesia, agitation, emotional lability (including crying and mood fluctuations).

In studies that used a tapering regimen, symptoms reported during the taper phase or upon discontinuation of paroxetine at a frequency of at least 2% of patients and occurred at a rate at least twice that of placebo were: emotional lability (including crying, mood fluctuations, self-harm, suicidal thoughts and attempted suicide), nervousness, dizziness, nausea and abdominal pain (see section 4.4 Special warnings and special precautions for use)

Depression is over-diagnosed

This from today’s Guardian:

Too many people are being diagnosed with depression when they are merely unhappy, a senior psychiatrist said today.

Normal emotions are sometimes being treated as mental illness because the threshold for clinical depression is too low, according to Professor Gordon Parker.

Prof Parker said depression had become a “catch-all” diagnosis, driven by clever marketing from pharmaceutical companies and leading to the burgeoning prescription of antidepressant drugs.

Writing in the British Medical Journal (BMJ), he said the drugs were being marketed beyond their “true utility” in cases in which people were unhappy rather than clinically depressed.

The psychiatrist, of the University of New South Wales, Australia, said the “over-diagnosis” of depression began in the early 80s, when the diagnostic threshold for minor mood disorders was lowered.

His 15-year study of 242 teachers found that more than three-quarters met the current criteria for depression.

Qualifying symptoms included “feeling sad, blue or down in the dumps” for two weeks, or appetite change, sleep disturbance, drop in libido and tiredness.

The psychiatrist said these symptoms were so common that most people would have them at some point in their lives. Under the current diagnosis guidelines, around one in five adults is thought to suffer depression during their lifetime.

The worldwide boom in the prescription of antidepressants in the past decade has led to criticism of drug companies’ marketing campaigns.

In the late 90s, drug companies in Japan prompted recognition of “mild depression” as a condition that required medication.

GlaxoSmithKline ran an awareness campaign in the country about mild depression, which said: “Depression is a disease that anyone can get. It can be cured by medicine. Early detection is important.”

Between 1998 and 2003, sales of antidepressants in Japan increase fivefold, according to the pharmaceutical industry analysts IMS Health. GlaxoSmithKline saw sales of its drug Paxil rise from $108m (£54,510,500) to $298m between 2001 and 2003.

However, mental health charities today rejected Prof Parker’s assertion that depression was over-diagnosed.

Marjorie Wallace, the chief executive of SANE, said: “It is better to risk over-diagnosis than to leave depression untreated. One in 10 people with severe depression may take their own life.”

Her view was supported by another study in the BMJ by Professor Ian Hickie, of Sydney University, who said the suicide rate had been reduced thanks to increased diagnosis of depression.

Ms Wallace added that depression could range from “feeling low to being so disabled that the person may be unable to get out of bed in the morning, sustain relationships or work”.

However, she acknowledged that doctors were being forced to over-prescribe antidepressants for low level depression because not enough money was being put into psychological therapies such as counselling.

Dr Andrew McCulloch, the chief executive of the Mental Health Foundation said it was “very unlikely” that depression was over-diagnosed in the UK. He said it was more the case that many people did not seek help because they did not recognise the symptoms of depression.

However, he also agreed that doctors were too readily providing medication when alternative treatments could be more effective.

“Medication is relied upon heavily in the UK by GPs and patients, and is often prescribed when an alternative might have been more suitable,” he said.

The World Health Organisation predicts that, by 2020, depression will be the second most serious disease globally after chronic heart disease.

So how could the diagnosis of Depression have become so widespread? Apart from drug company marketing, perhaps the answer lies in “DSM IV”.

I’m talking about the Diagnostic and Statistical Manual of Mental Disorders – this is the ‘bible’ when it comes to manuals of mental disorders…

The foremost definitions of depression are those developed by panels of experts convened by the American Psychiatric Association. The APA’s Diagnostic and Statistical Manual was first compiled in 1952 to assist the national census of mental disability, but has since been transformed. It was produced by a panel of experts from the American Psychiatric Association (APA) – an organisation close to and funded by the drug companies.

The fourth edition, known as DSM-IV, was published in 1994 and is now internationally recognised as the prime definition of how to recognise depression and, implicitly, when and how to treat it. DSM-IV definitions are also closely linked to those in the WHO’s International Classification of Diseases (ICD-10) and arguably now drive them.

In 1952 there were 106 different kinds of depression – by DSM IV in 1994 there were over 350 different kinds of depression listed.

In authenticating more and more diagnoses, the DSM process has helped to legitimise a dramatic increase in drug use (the dominant treatment mode) for conditions that become wider and wider in scope.

The work on DSM V is on-going thanks to a partnership between the American Psychiatric Association and the National Institute of Mental Health.

Whose best interests will be served by this new edition, I wonder?