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More trials of AstraZeneca

23 Mar, 10 | by BMJ

One down, 25,999 to go. Following allegations about the mendacious marketing of Seroquel (quetiapine) discussed in BBC Radio’s File on 4 programme, AstraZeneca has won the first of 26,000 lawsuits alleging that the drug was responsible for causing weight gain and diabetes.

The case was brought by Ted Baker, a 61-year-old Vietnam veteran who developed diabetes after taking Seroquel for three years for PTSD and depression (an unusual indication). The jury found in favour of AstraZeneca determining that the company provided adequate warning for prescribing doctors about the risk of diabetes.

A spokesman for AstraZeneca was more forthright in an email: “The heart of these cases are unproven claims that Seroquel causes diabetes. In case after case, jurors, judges and even plaintiffs’ lawyers themselves have found that plaintiffs simply cannot show through any accepted scientific method that AstraZeneca is responsible for their alleged injuries.” Actually, as the jury found that AZ gave adequate warning the question of Seroquel’s association with diabetes was not considered.

Reassured? Well take a look at this timeline of AZ memos, courtesy of BNET UK

DSM-5 online

11 Feb, 10 | by BMJ

Following a year of bitter exchanges about secrecy with accusations flying of vested interests and industry ties the American Psychiatric Association (APA) has posted the new, fifth edition of the Diagnostic and Statistical Manual of Mental Disorders online. Often called the psychiatrist’s bible but perhaps more aptly thought of as the psychiatrist’s cookery book the next update of the Manual is not due for release until May 2013 but the taskforce is looking for comments from clinicians, researchers and the general public (submissions welcome until April 20, 2010).

At first glance the most notable change is, of course, the decision to use an Arabic rather than Roman numeral in the title. Other changes include the likely introduction of Psychosis Risk Syndrome which will certainly prove controversial given the limited evidence for such a diagnosis having much predictive value. It looks like Compulsive shopping disorder and Internet addiction disorder are not going to make it in, but the currently topical Hypersexual disorder is. More to follow, but comments will be welcome here as well as at the APA site.

Skype, freemasonry, and the International Healing Foundation: more strange tales of reparative therapy

7 Feb, 10 | by BMJ

Following last year’s Sex and the City conference in London, Patrick Strudwick writes in the Independent of his undercover exploits in the world of reparative therapy: therapists claiming great results in switching a person’s sexual orientation and “helping people exit the gay world.”

Struck by a study published in BMC Psychiatry reporting that 1 in 6 of UK mental health professionals surveyed had tried to help lesbian, gay or bisexual patients change their sexual orientation, he went in search of such treatment and came across a psychotherapist (accredited with the British Association of Counsellors and Psychotherapists) and psychiatrist willing to oblige. And what a bizarre experience it proves to be:

I ask how she views homosexuality – as a mental illness, an addiction or an anti-religious phenomenon? “It’s all of that,” she replies. “At the heart of homosexuality is a deep isolation, which is where God needs to be”. A search for cause follows with questions about birth: “It’s just something I have noticed. Often [with homosexuality] it is quite traumatic, the baby was put into intensive care and because of the separation from the mother there can be that lack of attachment.” Excuse me? And what about family: “Any Freemasonry in the family? Because that often encourages it as well. It has a spiritual effect on males and it often comes out as same sex attraction.”

Sessions with the psychiatrist are by webcam, and include a recommendation to join Christian men’s groups. I’m not sure what the Royal College of Psychiatrists would make of that. If you want to know more, you should head for the International Healing Foundation where you can find therapists and ‘ministry leaders’ to guide you, and a compelling introductory video. Alternatively, if you’re interested in the evidence you might want to look at an overview on the RCPsych website. However, do bear in mind that, in the words of one correspondent, this may have been written by ‘active homosexuals’.

The trials of AstraZeneca

31 Jan, 10 | by BMJ

‘Key opinion leaders’ peddling propaganda for drug companies for a tidy sum, the burial of data on adverse effects from clinical trials, the promotion of new or exaggerated diagnoses to invigorate the market: a series of revelations, legal battles, and even a U.S. Senate investigation over the last year have brought to light the commanding influence that the pharmaceutical industry has over psychiatry. These corrupt practices are of course not exclusive to psychiatry, but it is here that they seem most pervasive.

The latest company in the dock is AstraZeneca facing over 10000 civil claims in the US with allegations that one of its top-selling drugs, the antipsychotic Seroquel (quetiapine), was marketed without warnings about the potential for significant weight gain and the development of diabetes. Adverse metabolic effects, notably obesity, have been a particular concern with the newer antipsychotic drugs so evidence of a reduced risk with Seroquel would give it an edge in a highly competitive market. But there is no such evidence as reported on this weeks BBC Radio 4 programme, File on 4 (if you don’t have access to BBC iPlayer you can read the transcript here). The programme includes an interview with a former medical manager for AstraZeneca in the UK, Dr John Blenkinsopp, who reports that he was expected to approve promotional claims that Seroquel was not associated with weight gain despite trial results to the contrary: “The clinical studies at the time of the launch of Seroquel showed patients developed significant weight gain, significant both statistically and clinically.”

“In the end I was put under quite a significant amount of pressure by the marketeers to sign off claims with regards to the lack of weight gain and I was unwilling to sign that off,” he told the programme, and whilst the drug was marketed in the US with these claims, in the UK there was only one such advertisement placed in the British Journal of Psychiatry in 2004. It stated that Seroquel was “the only atypical with . . . favourable weight profile across the entire dose range.”

And the company’s response? Well, the ad had been targeted at “UK healthcare professionals who would have understood the statement in the broader context of the debate around weight gain and atypical antipsychotics in UK.” It was approved by staff “in the context of available clinical evidence at that time”. Hmmm… AstraZeneca have spent $520 million on settling two federal investigations into the marketing of Seroquel and with more litigation pending, the financial press is speculating that job losses are a likely consequence.

AstraZeneca certainly isn’t the first drug company to be caught out like this. Many of the major companies have settled charges of fraud, off-label marketing and other offences. Calls for tighter regulation and independent trials come and go but we have been here before, and doubtless, we will be here again.

Soldier Suicides

14 Jan, 10 | by BMJ

“Of the more than 30000 people who fall to suicide nationwide each year, 20 per cent are veterans. About 18 veterans commit suicide every day”. The US Veterans Affairs Secretary, Eric Shinseki, was speaking at the 2010 Departments of Defense and Veterans Affairs Suicide Prevention Conference – it’s hard to imagine the UK Ministry of Defence holding one.

Suicide in military and ex-military personnel is attracting headlines at the moment and a cohort study of veterans of the UK Armed Forces is the subject of this month’s EBMH Editor’s Choice (free to access). In common with the new US data young men (under the age of 25) are at particular risk, notably in the first two years post-discharge. The commentary points to evidence for pre-service vulnerability as a significant risk factor. Another one, presumably, is access to means i.e. weapons.

What would US health care reform mean for mental health?

8 Nov, 09 | by BMJ

“I look forward to signing comprehensive health insurance reform into law by the end of the year. ” President Obama sounds confident following the passage of the health bill through House of Representatives. Others are not so optimistic. Senator Graham from South Carolina says the bill “is dead on arrival in the Senate.”

Amid all the furore about the supposed superiority, or not, of health care in the US, there has been little mention of mental health. It’s not clear what the bill as it stands would add other than the requirement that all health insurance plans would provide mental health and substance misuse coverage at the same level (parity) as general medical care, which is obviously a good thing. Jessa Crispin from The Smart Set magazine writes here about the difficulties involved in getting treatment for mental illness in the States, and even with insurance the hurdles can be pretty daunting. I’d like to think that signing up for a drug trial just to get hold of some antidepressants and follow up care would be unthinkable here in our socialist or fascist (depending on your perspective) NHS.

Right to a fair trial: St John’s wort

29 Oct, 09 | by BMJ

The updated NICE guideline for depression is just out. Here is what it has to say about St John’s wort:

Although there is evidence that St John’s wort may be of benefit in mild or moderate depression, practitioners should:
• not prescribe or advise its use by people with depression because of uncertainty about appropriate doses, persistence of effect, variation in the nature of preparations and potential serious interactions with other drugs (including oral contraceptives, anticoagulants and anticonvulsants)
• advise people with depression of the different potencies of the preparations available and of the potential serious interactions of St John’s wort with other drugs.

Funny that. In the last issue of EBMH, Edzard Ernst, the professor of complementary medicine who has become the bête noire of the alternative medicine crowd was less dismissive. Reviewing the latest Cochrane update he concludes that there is now plenty of evidence demonstrating that SJW is an effective antidepressant and if you can avoid herb-drug interactions, it may be safer than conventional drugs. So why don’t we recommend SJW for depression?

I have written about SJW here before and was less than complimentary (ouch!). My scepticism was similar to the NICE position: you can’t be sure what you are getting, and patients thinking that it’s not really a drug mix it with prescription medication and run into trouble. Perhaps, however, there is more to it than that. Given the rather murky history of clinical trials and marketing with conventional antidepressants and the often marginal benefit over placebo it does seem as though when it comes to evidence we hold St John’s wort to a higher standard. Trawl through the rapid responses of a trial involving SJW and you will find a degree of nit-picking that is rarely seen with the SSRIs. This type of reader or reviewer bias is not much discussed and competing interest statements rarely include declarations of inherent prejudice. In this editorial for Clinical Evidence, Professor Ernst criticises the knee-jerk assumption that if a clinical trial of a complementary medicine shows efficacy it must be a flawed trial. So is St John’s wort being treated unfairly? The answer, I think, has to be yes.

IAPT: The best laid schemes

5 Oct, 09 | by BMJ

Oh dear, Lord Layard will not be happy, but Zoe Williams will be. It looks like the wheels may be coming off the UK government’s plans to provide cognitive behavioural therapy for all – Improving Access to Psychological Therapies. With reports that there aren’t enough suitably-qualified therapists to go around and that funding may be in jeopardy, The Observer reports:

A flagship government strategy to train an army of therapists to get the nation off antidepressants and into work could be dramatically scaled back amid claims it is experiencing problems. More here.

I wonder if there is any provision for psychotherapy in David Cameron’s ‘Get Britain Working’ programme?

Respecting the right to die…revisited

2 Oct, 09 | by BMJ

With the recording of a narrative verdict following the inquest, the death of Kerrie Woolterton is once again making headlines. I wrote about this case of a young woman presenting with self-poisoning and refusing treatment one year ago, in a blog which attracted some thoughtful comment. The coroner stated: “She had capacity to consent to treatment which, it is more likely than not, would have prevented her death. She refused such treatment in full knowledge of the consequences and died as a result.” Sheila McLean, a Professor of Law and Medical Ethics, concurs with this view and clarifies the law in a commentary for the BMJ. She is correct, of course, in highlighting that if Ms Woolterton was thought to have capacity to make a decision about her treatment at the time of assessment the presence of an advance directive was indeed irrelevant.

Yet I still find the outcome of this case troubling. We are relying on details of events reported by the media, but given the context of this woman’s suicide would the presumption that she had capacity to decline treatment be so straightforward? Professor McLean makes the point that the presence of mental illness or indeed personality disorder is not in itself evidence of a lack of capacity. I would agree, but that does not mean they have no potential to influence or impair decision-making. Ms Woolterton had repeatedly presented after self-poisoning and would have known that treatment would be offered. That she still chose to call an ambulance to take her to hospital, albeit that she stated she was only seeking comfort and company, suggests to me a degree of ambivalence.

Key to the concept of capacity is the determination that a person understands the information relevant to a decision, and can use or weigh that information as part of the process of making the decision. As a legal concept that’s pretty clear but in a clinical setting where so many factors can be at play that determination can become murky. And of course, people often do not say what they mean or mean what they say.

In the last year I have discussed this case with a range of clinicians, and although the majority state that given this scenario they would have questions about the patient’s capacity and opt to treat them in their best interests, opinions are mixed. So the outcome (life or death) may have as much to do with our variable views as any objective measure of capacity which makes me uneasy. Vivienne Nathanson, head of science and ethics at the BMA, said the Mental Capacity Act had clarified the law for doctors. Maybe so, but it hasn’t made challenging dilemmas such as this any easier to resolve.

Freakonomic Mental Health

1 Oct, 09 | by BMJ

More antidepressants please…and bump up the Ritalin too. That seems to be the suggestion from this study published by the National Bureau of Economic Research in the US, making a link between new drug treatments for depression and ADHD and falling crime rates (Hat tip: The Economist).

Since the 1990s violent crime rates have declined markedly (no, it’s true, really), especially in the US. Criminologists have struggled to explain the trends as the usual suspects seem to have had little impact. So enter the economists with their alternative explanations, such as Steven Levitt (he of Freakonomics fame) presenting evidence that legalizing abortion in the 1970s led to a decline in the number of young people at risk of criminality, thus reducing crime rates.

In their provocative paper, A Cure for Crime?, Dave Marcotte and Sara Markowitz use data on international drug sales and crime rates as well as more detailed US data from the National Comorbidity Study (showing that in those with a mental disorder the percentage receiving treatment has increased from 20 to 33%) and national prescribing rates to show that ‘the countries with the largest declines in crime rates in the 1990s were almost exclusively those with the fastest growth in SSRI sales’. Details of the analysis are in an ungated preliminary version of the paper here. To control for overall improvements in health care they also looked at the impact of the non-psychotropic medicines, statins and COX-2 inhibitors which have also seen a rapid growth in prescriptions, but here there was no effect. They found that that increased prescribing of psychiatric drugs, notably SSRIs and stimulants (Ritalin), were associated with a reduction in violent crime and go on to conclude:

“Our evidence suggests that, in particular, sales of new generation antidepressants and stimulants used to treat ADHD are associated with rates of violent crime, with weaker evidence that anti-psychotic medications played a role in declining crime rates. The magnitude of the elasticities estimated here are clearly small. We estimate that a one percent increase in the total prescription rate is associated with a 0.051 percent decrease in violent crimes. To put this in perspective, doubling the prescription rate would reduce violent crimes by 5 percent, or by about 27 crimes per 100,000, at the average rate of 518 crimes per 100,000 population. While doubling the prescription rate seems like a large change, it has been estimated that 28 percent of the U.S. adult population in any year has a diagnosable mental or addictive disorder, yet only 8 percent seeks treatment (USDHHS 1999). Doubling the treatment rate would still leave a substantial portion of the ill untreated.

From the beginning to end of our panel, prescriptions per visit increased by 41 percent. Our elasticity estimates imply that this would reduce the total number of violent crimes committed by about 35,000. In fact, the total number of violent crimes reported to police declined by 300,000 during the period. Our estimates imply that just under 12 percent was due to expanded mental health treatment.”

Medical journals tend be dismissive of natural experiments and ecological studies such as this, considering them pretty weak evidence. But given that questions like this are never going to be answered by randomized controlled trials, if the methods are robust some freakonomic epidemiology may be just what we need.

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