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

Abstract and Introduction


Purpose: Most patients with depression are treated by general practitioners, and most of those patients prefer psychotherapy over pharmacotherapy. No network meta-analyses have examined the effects of psychotherapy compared with pharmacotherapy, combined treatment, care as usual, and other control conditions among patients in primary care.

Methods: We conducted systematic searches of bibliographic databases to identify randomized trials comparing psychotherapy with pharmacotherapy, combined treatment, care as usual, waitlist, and pill placebo. The main outcome was treatment response (50% improvement of depressive symptoms from baseline to end point).

Results: A total of 58 studies with 9,301 patients were included. Both psychotherapy and pharmacotherapy were significantly more effective than care as usual (relative risk [RR] for response = 1.60; 95% CI, 1.40–1.83 and RR = 1.65; 95% CI, 1.35–2.03, respectively) and waitlist (RR = 2.35; 95% CI, 1.57–3.51 and RR = 2.43; 95% CI, 1.57–3.74, respectively) control groups. We found no significant differences between psychotherapy and pharmacotherapy (RR = 1.03; 95% CI, 0.88–1.22). The effects were significantly greater for combined treatment compared with psychotherapy alone (RR = 1.35; 95% CI, 1.00–1.81). The difference between combined treatment and pharmacotherapy became significant when limited to studies with low risk of bias and studies limited to cognitive behavior therapy.

Conclusions: Psychotherapy is likely effective for the treatment of depression when compared with care as usual or waitlist, with effects comparable to those of pharmacotherapy. Combined treatment might be better than either psychotherapy or pharmacotherapy alone.


Hundreds of randomized trials have examined the effects of pharmacologic and psychologic treatments for depression.[1,2] However, the majority of depressed patients are treated in primary care, and relatively few of have focused on primary care.[3,4] The results for treatments across varying settings might not be valid for patients in primary care.

Antidepressant drugs and psychotherapy have small, positive effects on depression. Both treatment modalities have comparable effects in primary care.[5] For the longer term, psychotherapy might have better outcomes than pharmacotherapy.[6,7] Many general practitioners (GPs) are inclined to prescribe mainly antidepressant drugs,[8] whereas 75% of patients prefer psychotherapy.[9–11]

Conventional meta-analyses have shown that psychotherapy is effective for patients in primary care.[12–18] A network meta-analysis (NMA) of psychotherapy for patients in primary care found few significant differences between types of therapy.[12] This is in line with meta-analyses across treatment settings, which consistently showed no relevant differences between therapies.[2,19]

An NMA of treatments for depression in primary care has been conducted but focused mostly on clinical differences between types of trials in this field.[20] To the best of our knowledge, no NMAs with a focus on outcomes have been conducted in which psychotherapy for patients in primary care is compared with pharmacotherapy, combined treatment, and control conditions. Network meta-analyses can compare several alternative treatments in a single analysis and are able to use direct and indirect data, thus making optimal use of all available evidence.[20,1]

We conducted an NMA comparing the effects of psychotherapy with those of pharmacotherapy, combined treatment, and control conditions for depression. We included studies focusing on major depression, persistent mood disorders (dysthymia), or both, as well as studies that included patients scoring high on self-rating depression scales.