Antidepressants: expectation predicts response; relapses

Antidepressants have been shown in a number of studies to offer no significant benefit beyond placebo except in some cases of very severe depression. A study just published in the British Journal of Psychiatry provides further evidence showing that there was no significant difference in outcomes between antidepressants and placebo, and the response to both was predicted by expectations. Moreover, antidepressants increase the vulnerability to relapses. The authors state:

"Pill-taking, expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder (MDD)."

So they examined the effects of medication, placebo and support on outcomes in 88 subjects randomized to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication: venlafaxine (Effexor®);   duloxetine (Cymbalta®); escitalopram (Lexapro®). Their data showed virtually no difference between medication and placebo:

"Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone. Therapeutic alliance predicted response to medication and placebo; expectations of medication effectiveness at enrollment predicted only placebo response."

In other words, pills—either the medication or placebo—with supportive care were equally better than supportive care alone.A commentator writing in Medscape Medical News distilled the results:

"People's expectations about how effective their antidepressant medication is going to be almost entirely predicts their response to it, such that giving patients a placebo pill as active therapy during an 8-week period results in very similar reductions in symptoms...Very importantly as well, researchers observed that the strength of the therapeutic alliance with research personnel was significantly associated with clinical outcomes whether patients were on medication or placebo."

Antidepressants for severe depression

Medscape Medical News also quotes Irving Kirsch, PhD, director of the Program in Placebo Studies, Harvard Medical School who commented on the study and the effects of medication in very severe depression:

"It's not that severely depressed patients get any better response to the antidepressant, it's just that they don't get as much response to placebo."

Increased tendency to relapse after antidepressants

"Compared to other treatments, including psychotherapy, long-term effects for antidepressants seem to be worse, because relapse rates seem to be worse on antidepressants," he said.For example, studies have shown that if one group of depressed patients is given antidepressants and another receives organized physical activity, "you get a much higher relapse rate in the group given antidepressants at 1 year than in the exercise group," Dr. Kirsch said.Moreover, if antidepressants are added to the exercise group, "antidepressants seem to produce a greater risk of relapse," he noted. "So over the long term, antidepressants seem to induce a vulnerability for recurrent episodes more than other treatments."Dr. Kirsch feels that if antidepressants are to be used at all, they should only be used in extremely severe depression and only after other treatments have been tried and found not to work."

Discontinuing antidepressants

If after an interval of 6 to 8 weeks, antidepressants themselves do not seem to be working, "they should be discontinued," said Dr. Kirsch."We know that antidepressants can cause some harm, and if you are not getting any benefit, there is no reason to continue them, especially given that there is this possibility for enhancing vulnerability to relapse."