A problem with placebo-controlled trials?

Following advice from the Committee on Safety of Medicines, the only SSRI-type anti-depressant that UK clinicians can prescribe to children and teenagers is fluoxetine. The risk of suicide and self-harm associated with the use of the other drugs in the SSRI family has been judged to outweigh their benefit.

But speaking at a conference at the Institute of Psychiatry recently, Dr. Paramala Santosh, Consultant in Developmental Neuropsychiatry and Neuropharmacology at Great Ormond Street Hospital, said that the absolute size of the benefit of the banned drugs was often no less, and sometimes more than the effect size found for fluoxetine – it’s just that in the trials for the banned drugs, the size of the placebo effect had been so much larger.

Could this be a fundamental flaw in placebo-controlled trials? The effectiveness of drugs is measured against a placebo effect, but the size of that placebo effect isn’t constant and varies from one trial to another. So potentially, an inferior drug could be deemed effective in a trial where the placebo effect was weak.

Of course NICE guidelines state psychotherapy should be the first line treatment for depressed children, but with too few therapists available, it’s vital that effective drugs aren’t banned unnecessarily.

A few more details:

Santosh said that SSRIs were associated with suicide in adults too, it’s just that their effectiveness had been demonstrated (in placebo-controlled trials) and so benefit was seen to outweigh risk.

Another problem with this issue is that clinicians often prescribe SSRIs to clients they believe may be at risk of suicide because an SSRI overdose is not lethal. Cases such as these could skew trials examining the risk of SSRIs.

A new paper in Drug Safety shows that following the Committee on Safety of Medicines advice, children are being prescribed fewer SSRIs but that prescription rates for fluoxetine and other non-SSRI antidepressants haven’t risen: the implication being that children aren’t being given the alternative treatments they need.

2 thoughts on “A problem with placebo-controlled trials?”

  1. Really interesting. Presumably you could look at the original papers and see how big the placebo effect was? Some variation in the size of placebo effect would be expected – is Dr Santosh suggesting that there is systemmatic variation between different drug trials?

  2. hi tom
    yeh, he basically said that the placebo effect in trials for the banned drugs was larger than it had been in the trials demonstrating the efficacy of fluoxetine. i don’t have any more detail on that unfortunately. he also said that for other conditions where efficacy of ssri’s had been demonstrated (e.g. OCD), the placebo effect had been smaller there too. so you end up with a weird situation: drugs for conditions (like OCD) that are less responsive to placebo effects, don’t have to demonstrate as great an impact on symptoms (to be deemed effective), compared with drugs being tested for conditions ilke depression, that are highly responsive to placebo effects.

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