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Section Free  - Quick Takes

05. A Network Meta-Analysis of the Effects of Psychotherapies, Pharmacotherapies, and Their Combination in the Treatment of Adult Depression

Published on September 1, 2020 Expired on April 1, 2023

James Phelps, M.D.

Research Editor - Psychopharmacology Institute

Key Points

  • A recent network meta-analysis suggests that for adult depression, current practice is not optimal.
  • Combined pharmacotherapy and psychotherapy are better than either alone; psychotherapy is equal in efficacy to pharmacotherapy with fewer side effects.
  • In long-term studies, psychotherapy outcomes are better than pharmacotherapy.

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For an adult with depression, which is the best treatment: Psychotherapy, an antidepressant, or both? Whatever is your opinion, you will likely find support for that in this article, except for 1 approach, the most common one.

Let’s look at another network meta-analysis from Andrea Cipriani and colleagues––a team led here by psychotherapy expert Pim Cuijpers from the Netherlands. You may have heard earlier Quick Takes on network meta-analyses about antidepressants and antipsychotics. Overall, as a clinician, those did not seem to provide anything surprising or new, no reason to change routine treatment. However, this new network meta-analysis on psychotherapy vs pharmacotherapy might be different.

Remember that where meta-analyses compare two treatments––usually drug vs placebo––network meta-analyses make comparisons between multiple treatments. They are like head-to-head trials, without the trials, using what they call indirect comparison. It means that you can compare a trial of treatment A vs treatment B, another trial of B vs C, and C vs D, and D vs E. And through that network, you compare A vs E. These indirect comparisons have the same limitations as any meta-analysis; namely, are the studies on which they are based combinable? Are the populations similar enough? Was the study design, such as duration or titration, similar enough? Are the outcome measures comparable? The whole idea is inherently weak, but when it is done rigorously and with a vast number of studies––like 100 studies and 1200 patients as in this new piece from Cuijpers and Cipriani and colleagues––it might be useful.

How about psychotherapy vs pharmacotherapy for adult depression? Which one do you start? How often do you combine them? Well, here is the authors’ conclusion: “A significant proportion of patients with depression receive psychotropic medication without psychotherapy. The results of our meta-analysis suggest that this is probably not the optimal option.” Then, what is optimal? Either combination or psychotherapy alone, because combination had better outcomes than either alone in this network meta-analysis. Also, psychotherapy had higher acceptability, which was defined as fewer study dropouts. However, several qualifications should accompany this conclusion. Most are the inherent limitations of network meta-analyses. Psychotherapy, for example, was a lumped category including CBT, IPT, problem-solving therapy, and a scattering of others, including dynamic and behavioral activation therapy, and several more. Pharmacotherapy included many studies using tricyclics—nearly 25% by my eyeball analysis of the table that displays all the reports analyzed.

The authors performed subanalyses looking at moderate vs severe depression, and the conclusion was the same. The combination was better than either alone. Medication and psychotherapy were equal in efficacy. Then, they looked at the long studies, 6 to 12 months in duration, and again, the combination of medications and psychotherapy was better than either alone. However, in the long term studies, psychotherapy had slightly better efficacy than pharmacotherapy.

In conclusion, if you are a dedicated pharmacotherapist, you would not likely find that these results are particularly compelling. On the other hand, if you think psychotherapy should be used routinely, these results support you. However, I think the most significant question mark on our field right now is: How risky are antidepressants when used long term, as so many are? Evidence is emerging that discontinuing antidepressants after long-term use is difficult, sometimes extremely so for a substantial percentage of patients. If that is so, then this new network meta-analysis could support a position that is far from our current norms, namely, that psychotherapy should be the default treatment for adult depression, not pharmacotherapy. Well, stay tuned for more on that because surely more is coming. For more on this particular study, you will want to dig into the paper and look at Table 1—which goes on for 3 pages—displaying all the studies analyzed, including the type of therapy and the medications used. If you want more information about network meta-analysis, take a look at a different article that we have linked here by Tonin et al. about this technique.

Abstract

A Network Meta-Analysis of the Effects of Psychotherapies, Pharmacotherapies and Their Combination in the Treatment of Adult Depression

Pim Cuijpers, Hisashi Noma, Eirini Karyotaki, Christiaan H Vinkers, Andrea Cipriani, Toshi A Furukawa

No network meta-analysis has examined the relative effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression, while this is a very important clinical issue. We conducted systematic searches in bibliographical databases to identify randomized trials in which a psychotherapy and a pharmacotherapy for the acute or long-term treatment of depression were compared with each other, or in which the combination of a psychotherapy and a pharmacotherapy was compared with either one alone. The main outcome was treatment response (50% improvement between baseline and endpoint). Remission and acceptability (defined as study drop-out for any reason) were also examined. Possible moderators that were assessed included chronic and treatment-resistant depression and baseline severity of depression. Data were pooled as relative risk (RR) using a random-effects model. A total of 101 studies with 11,910 patients were included. Depression in most studies was moderate to severe. In the network meta-analysis, combined treatment was more effective than psychotherapy alone (RR=1.27; 95% CI: 1.14-1.39) and pharmacotherapy alone (RR=1.25; 95% CI: 1.14-1.37) in achieving response at the end of treatment. No significant difference was found between psychotherapy alone and pharmacotherapy alone (RR=0.99; 95% CI: 0.92-1.08). Similar results were found for remission. Combined treatment (RR=1.23; 95% CI: 1.05-1.45) and psychotherapy alone (RR=1.17; 95% CI: 1.02-1.32) were more acceptable than pharmacotherapy. Results were similar for chronic and treatment-resistant depression. The combination of psychotherapy and pharmacotherapy seems to be the best choice for patients with moderate depression. More research is needed on long-term effects of treatments (including cost-effectiveness), on the impact of specific pharmacological and non-pharmacological approaches, and on the effects in specific populations of patients.

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Reference

Cuijpers, P., Noma, H., Karyotaki, E., Vinkers, C. H., Cipriani, A., & Furukawa, T. A. (2020). A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry, 19(1), 92-107.

Tonin, F. S., Rotta, I., Mendes, A. M., & Pontarolo, R. (2017). Network meta-analysis: a technique to gather evidence from direct and indirect comparisons. Pharmacy Practice, 15(1), 943.

Learning Objectives:

After completing this activity, the learner will be able to:

  1. Evaluate the evidence implicating oral contraceptives in altered HPA axis physiology and consider the clinical implications thereof. 
  2. Evaluate the outcomes in patients who have stopped taking clozapine after taking it for a year or more, comparing the restarting of clozapine vs some other antipsychotic vs no antipsychotic at all.
  3. Compare the data presented in a new study of lumateperone with the balanced view of an accompanying editorial.
  4. Compare their clinical experience with lithium to new data in terms of both the impact of stopping the drug (measured by hospitalization rate) and the rate at which patients stop it due to various side effects.
  5. Evaluate a recent network meta-analysis (with a reminder on how NMAs work) regarding optimal treatment for adult depression: Should you start with psychotherapy, pharmacotherapy, or both? 

Original Release Date: September 1, 2020

Review and Re-release Date: March 1, 2023

Expiration Date: April 1, 2023

Relevant Financial Disclosures: 

James Phelps declares the following interests:

- McGraw-Hill:  book on bipolar disorder

- W.W. Norton & Co.:  book on bipolar disorder

All of the relevant financial relationships listed above have been mitigated by Medical Academy and the Psychopharmacology Institute.

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