Therapy Gets More Effective Over Time While Antidepressants Decrease in Effectiveness

New review of long-term depression data finds psychotherapy more effective over time whereas antidepressants decrease in effectiveness.


In a new article, researchers Susan McPherson and Michael Hengartner examine data on long-term depression outcomes. Their study was conducted in anticipation of forthcoming depression treatment guideline revisions by the National Institute for Health and Care Excellence (NICE). Their results demonstrated that antidepressants become less effective over time, whereas psychological therapies tend to increase in effectiveness.

Previously, NICE excluded analyses of long-term depression trials in their guidelines because the number of studies on long-term depression was insufficient. This decision was met with pushback, however, because long-term studies, which examine the prognosis of depression beyond the average 10-weeks of treatment, are a crucial source of evidence.

McPherson and Hengartner argue that “if it is possible to agree that good-quality, long-term trial data is the best possible evidence for long-term conditions, then the paucity and variable quality of this data should not be a reason to exclude it in analyses used to inform depression guideline recommendations.”

NICE has recently agreed to consider these data for the forthcoming revision. In response, McPherson and Hengartner conducted a review of the available evidence on long-term depression outcomes to inform the revision process. They write:

“Stakeholders have argued that long-term outcomes provide the ‘best-possible evidence’ and NICE executives have recently agreed to look at the issue again. We examine available data to illustrate how NICE could make use of this evidence.”

Their analysis found “that antidepressants are consistently less effective than either psychological treatment alone or in combination with antidepressants over the long term.”

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Among the studies on depression outcomes synthesized by NICE, long-term depression trials have been grouped into two separate categories: “treatment-resistant depression” and “chronic depression.” However, because both “treatment-resistant” and “chronic” trials tend to feature instances of depression occurring in “episodes” that last two years or more, the researchers did not consider them to be clinically meaningful distinctions.

In this review, they combined the two bodies of literature (on “treatment-resistant” and “chronic” depression). Their analysis included eleven studies that examined depression at the 6-month mark of treatment or later. The treatments in these studies varied, featuring a combination of antidepressant and psychological therapies (e.g., peer support, interpersonal therapy, cognitive behavioral therapy, group therapy).

McPherson and Hengartner examined the effect sizes of antidepressants at treatment completion and follow up and compared them to the effect sizes of psychological treatments at treatment completion and follow up.

Psychological treatments appeared to increase in effectiveness over time, except for cognitive-interpersonal group psychotherapy, which decreased in effectiveness over time, and cognitive-behavioral analysis system of psychotherapy, which had mixed results. Antidepressants were consistently less effective over time when compared to psychological treatments alone and psychological treatments in combination with antidepressants.

There are several limitations to consider when interpreting these findings. Inconsistencies across studies, such as the variability in design and differential effects caused by underreporting harms, side effects, and tolerability in psychological treatments versus antidepressant trials, serve as some examples. “Therefore,” the authors write, “the findings here are not presented as a standalone meta-analysis and should be interpreted with caution.”

NICE guidelines, however, provide a GRADE of trials that may account for this bias when applying findings toward guideline development.

Also, it is important to examine the supplementary data on long-term outcomes of depression that support these findings. For example, other studies have illustrated that recurrence of depression is more likely for those taking antidepressants than those who were administered a placebo. Moreover, the longer a person has been taking antidepressants, the more likely it is that they will experience depression relapse. These outcomes have been interpreted to represent either a result of increased tolerance to antidepressants or the effects of antidepressant withdrawal.

Naturalistic cohort studies indicate that using antidepressants in the long-term has worse results than short-term use, and non-pharmacological treatments result in more promising outcomes than long-term use of antidepressants. Furthermore, research finds that it is difficult to stop taking antidepressants after extended use.

Indeed, some patients may develop a dependency on antidepressants, and some who have used antidepressants for an extended amount of time report feeling addicted. Adding to the complications of antidepressant use are the burdensome side effects that pose significant health complications such as obesity, hepatotoxicity, and cardiovascular events.

Therefore, despite the tentative nature of these findings, they present important data, supported by evidence from other clinical trials that can be considered in treatment guidelines. McPherson and Hengartner conclude:

“Tentative analyses of long-term outcome data reveal an important clinical picture, which is supported by evidence from other forms of longitudinal research. Although the evidence remains to be appropriately evaluated with GRADE methodology, it is nevertheless important to consider it in the guideline because of the effect NICE guidelines have globally on patient care as well as ongoing and future research priorities.”



McPherson, S., & Hengartner, M. P. (2019). Long-term outcomes of trials in the National Institute for Health and Care Excellence depression guideline. BJPsych Open5(5). DOI: 10.1192/bjo.2019.65 (Link)


  1. However, most are treated with a combination of the two. You can do therapy alone, or drugs alone, but what if you do both drugs and therapy?

    I’d guess as the drug use increases, which invariably it will, the quality of therapy decreases. You might be falling asleep or unable to concentrate on a therapy session. Or the whole session might consist of a sunscreen lecture. You might be so unmotivated that you didn’t shower before therapy, so the whole session focuses on getting you into the shower. I have had countless therapy sessions where I asked them why I was getting edema and muscle cramps. It was from kidney disease from lithium, but this was really waste. Why didn’t they just come out with it and tell me I had kidney disease, when undoubtedly, the KNEW all along?

    In the end, therapy didn’t just suck. It was a danger to me, and I got out.