Summary: A clinical overview published in the Australian Journal of General Practice challenges the prevailing scientific consensus on long-term antidepressant use. The review identifies a fundamental flaw in many relapse prevention trials: researchers often mistake withdrawal symptoms for a true return of depression, which may overstate the benefits of continuing medication beyond one year.
Key Facts
- The 12-month efficacy deficit: The review found little robust evidence that antidepressants reliably prevent depressive relapse beyond a 12-month treatment period.
- The discontinuation design flaw: Most relapse prevention trials compare people who stay on medication with those who stop abruptly or quickly, creating conditions that commonly provoke withdrawal.
- The withdrawal masking problem: Because these studies do not distinguish withdrawal symptoms from clinical relapse, signs such as anxiety, insomnia and low mood are often misclassified as a return of depression.
- Small short-term benefits: Short-term randomized trials generally show only modest advantages of antidepressants over placebo, raising questions about long-term effectiveness when trial design is taken into account.
- Documented long-term harms: Evidence links prolonged antidepressant use to sexual dysfunction, emotional blunting, cognitive difficulties, weight gain and higher risk of physical health problems in older adults.
- “Set and forget” prescribing: Many people stay on antidepressants for extended periods: nearly one in seven Australians take them and about a third of users remain on medication for more than a year, often prescribed by general practitioners outside strict guideline criteria.
- Escalating discontinuation risks: Withdrawal risk appears to rise with longer duration of use, supporting the need for revised guidance that prioritizes slow, individualized dose tapering.
Source: University of Adelaide. Researchers from the University of Adelaide and The University of Queensland contributed to the clinical overview, which appears in the Australian Journal of General Practice.
Associate Professor Mark Horowitz, from the University of Adelaide’s School of Medicine, explains that much of the evidence supporting long-term antidepressant treatment comes from “discontinuation” trials. In these studies, people already taking medication are randomized to either continue treatment or stop it abruptly or rapidly. Because withdrawal symptoms can closely resemble depressive relapse, the trials risk conflating the two and overstating the protective effect of continued medication.
Short-term trials show only modest differences between antidepressants and placebo. The authors of the review argue that some apparent long-term advantages may reflect suppression of withdrawal symptoms rather than true prevention of depression or anxiety. They also emphasize accumulating evidence of harms associated with extended use, and note that withdrawal syndromes can be severe and persist for months or even years.
“Symptoms such as anxiety, low mood and insomnia occur in both withdrawal from antidepressants and a return of depression,” says Associate Professor Horowitz. “Because these studies do not distinguish between them, they commonly mislabel withdrawal as relapse.” He compares the logic to an absurdity: if stopping cigarettes made someone feel worse and that were taken as proof they should keep smoking, no one would accept that conclusion. Yet the same pattern of evidence is sometimes used to justify indefinite antidepressant treatment.
The review calls for clinical guidelines to be updated to reflect the absence of convincing long-term benefit and the presence of potential harms. The authors recommend regular review of antidepressant treatment, shared decision making about continuation versus discontinuation, and greater emphasis on slow, individualized tapering plans when stopping medication.
Professor Katharine Wallis, Head of General Practice at The University of Queensland Medical School, notes a shift in clinical thinking: “As GPs, we are becoming more aware of the limited benefits and potential harms of long-term antidepressant use and the need to move away from a ‘set and forget’ prescribing model. There should be stronger support for informed patient choices and gradual dose reduction.”
The authors suggest broader adoption of non-drug approaches, such as psychological therapies, which may offer more durable benefits for some patients. They also advise correcting misconceptions about a simplistic “chemical imbalance” explanation for depression and ensuring clinicians can distinguish between withdrawal and relapse.
Key Questions Answered:
A: Many trials use a discontinuation design that confuses abrupt stopping with disease return. When medication is stopped quickly, withdrawal symptoms such as low mood and insomnia can appear, and these effects are often recorded as relapse rather than identified as withdrawal.
A: Prolonged use has been associated with sexual dysfunction, emotional numbing, cognitive impairment, weight gain, increased physical health risks in older adults, and a rising chance of severe or prolonged withdrawal symptoms when stopping.
A: Guidelines should acknowledge that long-term effectiveness is unproven, recommend routine review of ongoing treatment, require plans for gradual tapering when discontinuing, and promote non-drug treatments and better education about withdrawal and the limits of the “chemical imbalance” narrative.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by the editorial team.
- Additional context was added by staff to clarify clinical implications and recommendations.
About this psychopharmacology research news
Author: Jessica Stanley
Source: Adelaide University
Contact: Jessica Stanley – Adelaide University
Image credit: Neuroscience News
Original Research: Open access. “Continuing antidepressants or not: Evaluating the potential benefits and harms” by Mark A. Horowitz, Katharine A. Wallis, and Joanna Moncrieff. Australian Journal of General Practice. DOI: 10.31128/AJGP-05-25-7690
Abstract
Continuing antidepressants or not: Evaluating the potential benefits and harms
Background
Many people use antidepressants longer, and for less severe symptoms, than guidelines recommend. Recent discussions on stopping antidepressants have not always addressed key weaknesses in the evidence base that supports continued long-term treatment.
Objective
To critically evaluate the evidence for continuing antidepressants beyond 12 months and to assess potential benefits and harms of long-term use.
Discussion
The primary evidence for long-term antidepressant use comes from discontinuation studies in which people already on medication are randomized to continue or stop. These trials typically do not differentiate withdrawal symptoms from relapse, so deterioration in the discontinued group is often labelled relapse and interpreted as proof that continued treatment prevents recurrence. This overlooks the possibility that staying on medication may simply suppress withdrawal effects. Given the lack of robust evidence for long-term benefit and the presence of documented harms, antidepressant treatment should be reviewed regularly, with shared decision making and individualized plans for tapering or alternative therapies.