Clinical trials with psychopharmacologic drugs–a regulatory point of view

Controlled, randomized, double-blind parallel-group clinical trials are needed to establish efficacy and safety of new psychopharmacological drugs. Usually this is done by clinical trials including placebo control. These placebo controlled trials have been critizized as being unethical in clinical situations where effective and acceptable treatment options are available. It has been argued that studies with potential new antidepressants or antipsychotics should employ only a comparator-controlled design, whereby new drugs have to be non-inferior or superior to existing treatment. However, sole acceptance of „superior“ compounds will hinder the development of more efficacious and better tolerated drugs. Moreover, acceptance of non-inferiority designs in psychopharmacology will be associated with the risk to approve ineffective compounds. In general both active-controlled designs require the inclusion of larger patient populations. Due to these methodological reasons placebo-controlled studies of new psychopharamcologic agents are still justified and necessary, both ethically and scientifically. Therefore, from a regulatory point of view, three-arm studies including a standard reference, new active substance and placebo represent the preferred study design, which allows the most comprehensive interpretation of study results.