Everybody has won and all must have prizes

Fiona Godlee, BMJ editor, in her latest Editor's Choice, is pleased to see what she calls evidence that counters claims that antidepressants have little or no effect. She finds this evidence in an editorial that commented on a meta-analytic study, which found no substantial difference in efficacy between the second generation antidepressants.

The work that Godlee thinks "may well have dissuaded patients and some clinicians from considering or continuing antidepressants" is that of  Irving Kirsch, which I have discussed in a previous post. What the authors of the editorial say, which Godlee thinks counters Kirsch's work, is that the meta-analysis found that "[j]ust under two thirds of the patients responded to treatment by 12 weeks and just under half achieved full remission". They don't say compared to what or define response or remission. 

Before it can be concluded that this finding means that antidepressants are effective, it is necessary to ask what the controls were. People improve naturally from depression. There is a large placebo response to antidepressants. 

There is also a question about the definitions of response to treatment and remission in clinical trials. Fifty percent reduction in score severity is most commonly used as the measure of response. Many of these patients who are classified as responders nonetheless remain highly symptomatic. A reasonably low cutoff score on rating scales is usually proposed as the definition of remission. This is not the same as being completely asymptomatic.  So, the results noted by Godlee may not be as good as they seem. (See my previous blog entry, How easy is to treat depression?)

Moreover, most head-to-head comparisons of antidepressants do not include a placebo arm. Antidepressant response rates are higher in comparator trials compared to placebo-controlled trials, because of the greater expectancy effect as patients know they will definitely be given an antidepressant rather than have a chance of getting placebo. If all that is being suggested is that the effect size seems larger for trials comparing one drug with another rather than with placebo, this is not a new finding. 

What people find difficult, including the BMJ editor apparently, is accepting that randomised controlled trials of antidepressants (and probably drugs in the rest of medicine - see previous blog entry) have not eliminated expectancy effects because they are not really double-blind (see a critical exploration of the evidence). The throw-away remark in the BMJ editorial (the article is after all more about the comparative efficacy of second generation antidepressants than about the effectiveness of antidepressants as such) should have been subject to more scrutiny before publication. It then wouldn't have been taken up by the editor to undermine the challenge to the wish-fulfilling nature of antidepressant medication.

Conference programme

Psychosis risk syndrome at risk?

Article in The Sydney Morning Herald says Patrick McGorry has changed his mind about including attenuated psychosis syndrome in DSM-5. This coincides with a commentary in The Lancet also concluding that inclusion of this diagnosis would be premature. Even if it is a valid syndrome, a Cochrane review says there is no conclusive evidence that people in the prodrome of psychosis can be helped.

Peter Breggin falls out with David Healy over ECT

Peter Breggin has been critical of David Healy's views about ECT in a blog on The Huffington Post. I also wasn't that impressed with David in a book review I did some years ago.

Psychiatric drugs just as ineffective as other drugs

A BJPsych article, which claims it is the "first attempt to provide a panoramic overview of major drugs", concludes that psychiatric drugs are not generally less efficacious than other drugs. The paper has been commented on in a BMJ news item. The authors of the article note the questioning in the literature of the efficacy of antidepressants, cholinesterase inhibitors for Alzheimer's disease and lithium prophylaxis in bipolar disorder. They also reference a review of their own, which found "a smaller antipsychotic drug-placebo difference than we had intuitively expected".

They say these reports inspired an article in The New Yorker which summarised them. They then go on to suggest that a vocal antipsychiatry movement has been fuelled by this critique of psychiatric medication. To support their argument, they reference Medication madness by Peter Breggin and The emperor's new drugs by Irving Kirsch. I have mentioned the latter in a previous post. Actually, it's not anti-psychiatry to practice in an evidenced-based way. What people seem to be finding difficult is coping with the reality of the evidence.

The study confirms that the highest effect sizes in psychiatry come from withdrawal studies of maintenance treatment. This is higher than that found for acute treatment. As the effect size is small for acute treatment, it is possible the finding is due to an artefact caused by the fact that randomised controlled trials are not as double-blind as is commonly assumed (see, for example, From placebo to panacea: Putting psychiatric drugs to the test). The bias introduced through unblinding could potentially explain the results. As I have mentioned before (eg. see previous post), the higher effect size in withdrawal studies could be due to the nocebo effect of discontinuing medication compounding unblinding.

The fact that non-psychiatric drugs have similar effect sizes in clinical trials should not be interpreted as meaning that psychiatric drugs are effective, but that medical as well as psychiatric clinical trials are subject to the same biases of unblinding. Secondary prevention of cardiovascular events with aspirin or statins has even lower effects sizes than those for psychiatric treatment. It is possible that so-called "hard" endpoints such as death could be affected by these same biases (see, for example, my eletter).