The investigation of the comparative efficacy of the combination of pharmacotherapy and psychotherapy versus either modality alone has to consider several methodological issues. Neglect of these methodological aspects can lead to severe pitfalls. Also, the interpretation of the results of such studies should be performed very carefully, considering several aspects. Among others, the following questions have to be addressed:

• – Was the study performed in a more psychopharmacology-oriented or more psychotherapeutically-oriented institution?

• – Were the patients acutely or chronically ill?

• – Were the patients already refractory to pharmacotherapy or psychotherapy prior to inclusion in the study?

• – Was the pharmacotherapy performed according to the state of the art?

• – Was the psychotherapy performed according to the state of the art?

• – Was the pharmacotherapy administered under double-blind conditions, using a placebo control or another kind of control?

• – Was the psychotherapy administered in the context of a pseudo placebo control group?

• – Was the sample size adequate for a confirmative trial?

Generally it has to be taken into consideration that it is much more difficult to prove efficacy of a combination therapy versus an active mono-therapy then to prove efficacy of a mono-therapy or combination therapy versus placebo. Overall, there seems to be evidence for superior efficacy of the combination of antidepressants with cognitive behaviour therapy, especially in certain subgroups of patients.