Summary: A new clinical overview challenges the scientific consensus on long-term antidepressant use, identifying a fundamental flaw in many relapse-prevention trials. The review finds that severe withdrawal symptoms—such as anxiety and insomnia—are often wrongly classified as a return of depression, inflating the perceived benefits of continued medication.
Key Facts
- The 12-month evidence gap: The review found little robust proof that antidepressants reliably prevent depressive relapse beyond 12 months of treatment.
- Flawed discontinuation design: Many relapse-prevention trials compare patients who continue medication with those who stop abruptly or rapidly, a design that confounds withdrawal with relapse.
- Withdrawal misidentified as relapse: Acute withdrawal symptoms—anxiety, low mood, insomnia—are frequently misinterpreted by researchers as a return of the original illness.
- Modest short-term benefits: Short-term randomized trials show only small differences between antidepressants and placebo in symptom improvement.
- Documented long-term harms: Prolonged antidepressant use has been associated with sexual dysfunction, emotional blunting, cognitive difficulties, weight gain, and increased physical-health risks in older people.
- “Set and forget” prescribing: A large proportion of prescriptions are issued in primary care, with many patients remaining on medication for years despite guideline recommendations for shorter courses.
- Rising withdrawal risk: Withdrawal problems tend to increase with duration of use, underscoring the need for gradual tapering and updated clinical guidance.
Source: University of Adelaide
Researchers: Contributors include investigators from the University of Adelaide and The University of Queensland. Their clinical overview is published in the Australian Journal of General Practice.
Associate Professor Mark Horowitz of the University of Adelaide’s School of Medicine explains that much of the evidence for long-term antidepressant effectiveness comes from so-called relapse-prevention trials. “These studies typically randomize people who are already taking antidepressants to either continue the drug or stop it abruptly or quickly. Because they rarely separate withdrawal symptoms from genuine clinical relapse, many apparent relapses may be withdrawal in disguise,” he said.
Short-term randomized controlled trials generally find only small advantages for antidepressants compared with placebo. The overview suggests that some of the apparent long-term benefit seen in continuation studies may result from suppressing withdrawal symptoms in the group that remains on medication, rather than from true prevention of depression or anxiety returning.
The investigators also emphasize growing evidence of harms associated with prolonged use. Reported problems include sexual dysfunction, reduced emotional responsiveness, cognitive impairment, weight gain, and a higher risk of physical-health issues among older adults. Withdrawal can be severe and persist for months or even years for some people.
“Symptoms such as anxiety, low mood and insomnia occur both in withdrawal from antidepressants and in a relapse of depression,” said Associate Professor Horowitz. “When studies do not tell these apart, withdrawal is commonly misclassified as relapse, which can lead clinicians and patients to believe long-term treatment is more beneficial than it actually is.”
The review authors argue that clinical guidelines should be updated to reflect the weak evidence for long-term effectiveness and the clear evidence for potential harms. They call for routine review of ongoing antidepressant treatment with shared decision-making about whether to continue, reduce, or stop medication.
Nearly one in seven Australians currently take antidepressants, and roughly one-third of those remain on them for more than a year. Much of this prescribing takes place in general practice, sometimes outside strict guideline criteria, which the authors describe as a problematic “set and forget” culture.
Professor Katharine Wallis, Head of General Practice at The University of Queensland Medical School, highlighted the need for greater awareness among primary-care clinicians. “We are becoming more aware of the limited benefits and potential harms of long-term antidepressant use,” she said. “There should be more emphasis on supporting patients to make informed choices and, when appropriate, on stopping medication by gradually reducing the dose.”
The authors recommend correcting misconceptions—such as simplistic appeals to a single “chemical imbalance” explanation for depression—improving recognition of withdrawal symptoms, and promoting non-drug options like psychological therapies, which may offer more durable recovery for some patients. They stress that careful, individualized tapering plans are essential for those discontinuing long-term therapy.
Key Questions Answered:
A: Many trial designs compare people who continue medication with those who stop abruptly. The abrupt-stopping group often experiences withdrawal symptoms—low mood, anxiety, insomnia—which can be misinterpreted as relapse, making continued treatment appear more protective than it truly is.
A: Prolonged use is associated with an accumulating range of side effects and health concerns, including sexual dysfunction, emotional blunting, cognitive problems, weight gain, and higher physical-health risks in older adults. Withdrawal severity also appears to increase with longer duration of use.
A: Guidelines should state clearly that long-term effectiveness is not well established, require regular treatment reviews, mandate planning for gradual tapering when stopping medication, and encourage accurate recognition of withdrawal and the use of non-pharmacological treatments where appropriate.
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 our staff to clarify clinical implications.
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 for longer periods and for less severe conditions than current guidelines recommend. Recent discussions have explored reasons to stop antidepressants but have often overlooked flaws in the evidence supporting long-term continuation.
Objective
To critically appraise the evidence for continuing antidepressants long-term (more than 12 months).
Discussion
The main evidence for long-term use comes from discontinuation studies that randomize people already taking antidepressants either to continue or to stop. These studies typically do not distinguish withdrawal symptoms from relapse. When worsening mood or anxiety occurs in the discontinued group, it is often labeled as relapse, and the findings are interpreted as proof that long-term therapy prevents recurrence. This interpretation overlooks the possibility that apparent benefits of continuing medication may instead reflect suppression of withdrawal symptoms. Given the limited robust evidence of long-term benefit and growing evidence of potential harms, antidepressant treatment should be reviewed regularly with shared decision-making about whether to continue, adjust, or discontinue therapy.