Double-Blind Randomized Placebo-Controlled Trials in the Treatment of Affective Disorders: Problems and Alternatives

Double-blind randomized placebo-controlled trials, in which a new approval-seeking drug is compared to placebo, are generally considered to be the gold standard for evaluating the efficacy of a psychopharmacological intervention in the treatment of affective disorders. However, this type of study has substantial limitations regarding the external validity of its results. Therefore, alternatives within randomized controlled trials, such as non-inferiority trials or study designs in which the new drug or placebo is given simultaneously on top of standard antidepressant or anti-manic treatment are of substantial interest. In addition, innovative statistical approaches such as marginal structural models or Q-learning should be employed to evaluate potential causal effects associated with different fixed treatment regimes that are realized in actual clinical practice and help to establish treatment recommendations that are tailored to individual patient characteristics. © 2015, Springer International Publishing AG.