Psychologic Treatment of Depression Compared With Pharmacotherapy and Combined Treatment in Primary Care

A Network Meta-Analysis

Pim Cuijpers, PhD; Matthijs Oud, MA; Eirini Karyotaki, PhD; Hisashi Noma, PhD; Soledad Quero, PhD; Andrea Cipriani, MD, PhD; Bruce Arroll, PhD; Toshi A. Furukawa, MD, PhD


Ann Fam Med. 2021;19(3):262-270. 

In This Article


In the present NMA, we found that combined treatment, psychotherapy, and pharmacotherapy were clearly more effective than CAU and waitlist conditions. We found no statistically significant differences between psychotherapy and pharmacotherapy. The magnitude of the effect was greater for combined treatment compared with psychotherapy and pharmacotherapy alone, although this was not significant in all analyses. We found no differences in acceptability between any of the conditions. Based on the evidence currently available, the present meta-analysis is the first to show these results in primary care.

Our present results are generally in line with a broader meta-analysis of trials across different settings.[55] In that study, the effects of combined treatment were found to be superior to psychotherapy or pharmacotherapy alone, whereas those of psychotherapy and pharmacotherapy were comparable.[55] In the present meta-analysis, combined treatment was not superior in all analyses; this might be related to the smaller number of trials and statistical power or to differences in the primary care populations. The broader meta-analysis also found that acceptability of psychotherapy and combined treatment were greater than that of pharmacotherapy.[55] The fact that this was not supported in the present study might, again, be related to lower power or to differences in the populations. Although the findings are not unique to primary care, they do indicate that combined treatment has the best effects and that pharmacotherapy and psychotherapy have comparable effects.

Several studies included in the present NMA focused on patients with moderate to severe depression, whereas patients in primary care usually suffer from mild to moderate depression. It is also assumed that antidepressant drugs work better for more severe depression.[56] The inclusion of these studies might therefore have resulted in an overestimation of the effects of pharmacotherapy in the present NMA.

There are several limitations to the present study. First, RoB was considerable in many studies, and publication bias was suspected for some comparisons. Second, waitlist was compared with psychotherapy only and did not form any closed loop; therefore, only indirect evidence was available. In addition, insufficient numbers of studies were available on long-term effects. Furthermore, most studies included mixed populations of patients with major depression and dysthymia, and outcomes might differ for those populations. Finally, previous research has indicated that there might be differences in efficacy and acceptability of specific types of drugs;[1] we merged all antidepressants into a single node.

Despite these limitations, we can conclude that psychotherapy and pharmacotherapy appear to be similarly effective for the treatment of depression compared with CAU or waitlist and that the effects of combined treatment might be superior to psychotherapy or pharmacotherapy alone. Treatments in primary care must be organized so as to accommodate any of these treatments in response to patients' preferences and values.