Study Points to Best Treatments for Depression in Primary Care

Kate Johnson

May 17, 2021

Psychotherapy and pharmacotherapy appear to be similarly effective for the treatment of depression, and a combination of both treatments might pack the biggest punch, according to a network meta-analysis (NMA) comparing either and both approaches with control conditions in the primary care setting.

The findings are important, since the majority of depressed patients are treated by primary care physicians, yet relatively few randomized trials of treatment have focused on this setting, noted senior study author Pim Cuijpers, PhD, from Vrije Universiteit Amsterdam, and colleagues, in the paper, which was published in Annals of Family Medicine.

"The main message is that clinicians should certainly consider psychotherapy instead of pharmacotherapy, because this is preferred by most patients, and when possible, combined treatments should be the preferred choice because the outcomes are considerably better," he said in an interview. Either way, he emphasized that "preference of patients is very important and all three treatments are better than usual care."

The NMA included studies comparing psychotherapy, antidepressant medication, or a combination of both, with control conditions (defined as usual care, wait list, or pill placebo) in adult primary care patients with depression.

Patients could have major depression, persistent mood disorders (dysthymia), both, or high scores on self-rating depression scales. The primary outcome of the NMA was response, defined as a 50% improvement in the Hamilton Depression Rating scores (HAM-D).

A total of 58 studies met inclusion criteria, involving 9,301 patients.

Treatment Options Compared

Compared with usual care, both psychotherapy alone and pharmacotherapy alone had significantly better response rates, with no significant difference between them (relative risk, 1.60 and RR, 1.65, respectively). The combination of psychotherapy and pharmacotherapy was even better (RR, 2.15), whereas the wait list was less effective (RR, 0.68).

When comparing combined therapy with psychotherapy or pharmacotherapy, the superiority of combination therapy over psychotherapy was only slightly statistically significant (RR, 1.35; 95% confidence interval, 1.00-1.81), while pharmacotherapy was only slightly inferior (RR, 1.30; 95% CI, 0.98-1.73).

"The significance level is not very high, which is related to statistical power," said Cuijpers. "But the mean benefit is quite substantial in my opinion, with a 35% higher chance of response in the combined treatment, compared to psychotherapy alone."

Looking at the outcome of remission, (normally defined as a score of 7 or less on the HAM-D), the outcomes were "comparable to those for response, with the exception that combined treatment was not significantly different from psychotherapy," they wrote.

One important caveat is that several studies included in the NMA included patients with moderate to severe depression, a population that is different from the usual primary care population of depressed patients who have mild to moderate symptoms. Antidepressant medications are also assumed to work better against more severe symptoms, added the authors. "The inclusion of these studies might therefore have resulted in an overestimation of the effects of pharmacotherapy in the present NMA."

Among other limitations, the authors noted that studies included mixed populations of patients with dysthymia and major depression; they also made no distinction between different types of antidepressants.

Psychotherapies Unknown, but Meta-Analysis Is Still Useful

Commenting on these findings, Neil Skolnik, MD, professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, said this is "an important study, confirming and extending the conclusions" of a systematic review published in 2016 as a Clinical Practice Guideline from the American College of Physicians.

"Unfortunately, the authors did not specify what type of psychotherapy was studied in the meta-analysis, so we have to look elsewhere if we want to advise our patients on what type of psychotherapy to seek, since there are important differences between different types of therapy," he said.

Still, he described the study as providing "helpful information for the practicing clinician, as it gives us solid information with which to engage and advise patients in a shared decision-making process for effective treatment of depression."

"Some patients will choose psychotherapy, some will choose medications. They can make either choice with the confidence that both approaches are effective," Skolnik elaborated. "In addition, if psychotherapy does not seem to be sufficiently helping we are on solid ground adding an antidepressant medication to psychotherapy, with this data showing that the combined treatment works better than psychotherapy alone."

Cuijpers receives allowances for his memberships on the board of directors of Mind, Fonds Psychische Gezondheid, and Korrelatie, and for being chair of the PACO committee of the Raad voor Civiel-militaire Zorg en Onderzoek of the Dutch Ministry of Defense. He also serves as deputy editor of Depression and Anxiety and associate editor of Psychological Bulletin, and he receives royalties for books he has authored or coauthored. He received grants from the European Union, ZonMw, and PFGV. Another study author reported receiving personal fees from Mitsubishi-Tanabe, MSD, and Shionogi and a grant from Mitsubishi-Tanabe outside the submitted work. One author has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation, and Angelini Pharmam, while another reported receiving personal fees from Boehringer Ingelheim, Kyowa Kirin, ASKA Pharmaceutical, and Toyota Motor Corporation outside the submitted work. The other authors and Skolnik reported no conflicts.

This article originally appeared on, part of the Medscape Professional Network.


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