Is the ongoing use of placebo in relapse-prevention clinical trials in schizophrenia justified?

Placebo-controlled randomised controlled trials (RCTs) continue to be required or recommended by regulatory authorities for the licensing of new drugs for schizophrenia, despite ongoing concerns regarding the risks to trial participants.

In this article we consider the scientific and ethical pros and cons associated with use of placebo in RCTs in schizophrenia, systematically review the published relapse-prevention placebo-controlled RCTs with second generation antipsychotics (SGAs) in schizophrenia, and examine the risks associated with these trials.

We identified 12 studies involving 2842 participants of which 968 received placebo. Relapse rates were 56% for placebo and 17.4% for active treatment groups. There is a lack of well-designed longitudinal studies investigating the psychosocial and biological consequences of exposure to placebo, to treatment discontinuation and to relapse in schizophrenia.

In the absence of such studies it is risky to assume that patients are not at risk of significant distress and long-term harm, and therefore it is difficult to justify the ongoing use of placebo in relapse-prevention RCTs in schizophrenia.