Psychotherapy in controlled psychopharmacology trials. Does it matter if we ignore it?

The controlled trial is now the standard for assessing efficacy of new treatments in Psychiatry, as it is in the rest of medicine. Psychiatric outcomes with treatment are influenced by concurrent psychosocial factors. Psychotherapy, alone or in combination with pharmacotherapy is an effective treatment. Thus, if concomitant receipt of psychotherapy is not controlled for in a psychopharmacology trial, outcome may be biased. In this study, all peer reviewed journal articles describing the results of randomized, controlled psychopharmacology trials in two separate years were carefully reviewed to assess the possible influence of control versus lack of explicit control for effect of concomitant psychotherapy on clinical outcome. One hundred sixteen articles, published in the years 1996 and 2000, were reviewed. Those with categorically positive or non-positive global outcome were assessed for description of concomitant receipt of psychotherapy by subjects randomized to different pharmacotherapy treatments. Description of comparability in potentially confounding demographic and clinical variables was present in all studies. Only 22% of 89 studies meeting inclusion criteria explicitly controlled for concomitant psychotherapy. Seventy five percent of 20 studies that did, and only 46% of 69 studies that did not, found different outcomes in groups randomized to different pharmacotherapy interventions (p=.024). This result was not accounted for by other aspects of study design such as placebo-vs.-active control comparison, trial size, length, geographic location, number of sites or authors, source of funding, or diagnostic composition)-suggesting that uncontrolled receipt of psychotherapy may reduce likelihood of finding a difference between a new treatment and a control pharmacotherapy intervention. If confirmed by further investigation, the results may warrant adoption of relevant recommendations for controlled trial design in psychopharmacology research. The method used in this report may be useful in other areas of controlled trial research to assess influence of confounding variables.