Summary: A clinical overview challenged the scientific consensus supporting long-term antidepressant use. The review unmasked a fundamental flaw in existing clinical trial designs.
Investigators revealed that the widely cited benefits of long-term treatment are significantly overstated, as historical relapse prevention trials routinely miscategorize severe medication withdrawal symptoms, like anxiety and insomnia, as a return of the patient’s underlying depression.
Key Facts
- The 12-Month Efficacy Deficit: The review found a profound lack of robust evidence proving that antidepressants effectively prevent depressive relapse beyond a 12-month treatment window.
- The Discontinuation Design Flaw: Relapse prevention trials typically compare patients who continue their medication against a group that stops abruptly or rapidly.
- The Withdrawal Masking Glitch: Because these historical studies fail to distinguish between acute withdrawal effects and actual clinical relapse, they miscategorize withdrawal symptoms as a return of depression.
- Exaggerated Baseline Improvements: Short-term trials indicate only minor differences in patient improvement when antidepressants are compared directly to a placebo.
- Compounding Long-Term Health Risks: The research highlights documented dangers tied to long-term use, including sexual dysfunction, emotional numbing, cognitive impairment, weight gain, and physical health complications in older adults.
- The “Set and Forget” Prescribing Culture: Nearly one in seven Australians currently take antidepressants, with a third remaining on them for over a year, frequently prescribed by general practitioners outside of strict guideline criteria.
- The Escalating Discontinuation Threat: Co-authors Associate Professor Mark Horowitz and Professor Katharine Wallis warn that withdrawal risks increase with the duration of use, demanding updated clinical guidelines and a shift toward slow, gradual dose tapering.
Source: University of Adelaide
Researchers from Adelaide University and The University of Queensland were involved in the clinical overview, which has been published in the Australian Journal of General Practice.
They found there was little robust evidence to suggest that antidepressants prevent relapse beyond 12 months and believe the widely cited benefits supporting long-term use may be overstated due to a fundamental flaw in research design.
“Much of the evidence supporting long-term antidepressant treatment comes from so-called relapse prevention trials,” said Associate Professor of Psychiatry Mark Horowitz, at Adelaide University’s School of Medicine.
“These studies typically compare patients who continue medication with those who stop abruptly or rapidly. Because they don’t distinguish between withdrawal symptoms and the return of depression, we believe many apparent relapses may actually be withdrawal effects from the medication.”
Short-term trials of antidepressants reveal only small differences in improvements when compared to a placebo. There was also some research indicating that the apparent benefit of long-term treatment may be due to the suppression of withdrawal symptoms rather than the true prevention of depression or anxiety.
The research also highlights growing evidence of risks associated with long-term use, including sexual dysfunction, emotional numbing, cognitive impairment, weight gain and increased risk of physical health problems in older adults.
Withdrawal symptoms can be severe and long-lasting, sometimes persisting for months or even years.
“Symptoms such as anxiety, low mood and insomnia occur in both withdrawal from antidepressants and a return of depression. As these studies do not distinguish between them, they will mis-categorise withdrawal as a return of depression as this is the focus of such studies,” said Associate Professor Horowitz.
“If the same approach was taken with cigarettes and feeling worse on stopping them was interpreted as evidence that people should continue smoking them, we know that would be absurd. But the same sort of evidence is used to recommend long-term antidepressants.
“Guidelines need to be updated to reflect that there are no good studies which show that antidepressants are effective in the long term.”
Nearly one in seven Australians are taking antidepressants, with a third of people staying on them for more than a year. Most of this medication is being prescribed by general practitioners, often in situations where guideline criteria may not be fully met.
“Concerningly, the risk of withdrawal effects appears to increase with the duration of use – one reason for stopping antidepressants sooner rather than later,” said Associate Professor Horowitz.
Researchers say many patients recover from depression without long-term medication and are calling for a re-think of how depression is treated long-term, noting that non-drug approaches such as psychological therapies may offer more durable benefits.
“As GPs, we are becoming more aware of the limited benefits and possible harms associated with long-term antidepressant use and the need to reconsider the ‘set and forget’ approach to prescribing these medicines,” said Professor Katharine Wallis, Head of General Practice at The University of Queensland Medical School.
“There is increasing emphasis on supporting patients to make informed choices about antidepressant use and to stop antidepressants by slowly decreasing the dose.”
Other recommendations include addressing misconceptions about depression being caused by a ‘chemical imbalance’, recognition that worsening symptoms on stopping antidepressants may be linked to withdrawal rather than relapse and wider adoption of gradual weaning strategies when discontinuing medication for long-term users.
Key Questions Answered:
A: Because the trials use a flawed design that mistakes stopping the drug for a return of the illness. When researchers abruptly stop a patient’s medication, the patient experiences severe withdrawal symptoms like low mood and insomnia, which the studies immediately miscategorize as a depressive relapse rather than a chemical withdrawal effect.
A: Prolonged use exposes patients to a compounding list of side effects and health complications. Evidence highlights long-term risks including sexual dysfunction, emotional numbing, cognitive impairment, weight gain, an increased risk of physical health problems in older adults, and a steadily rising risk of severe withdrawal.
A: Guidelines must be updated to explicitly state that long-term effectiveness is unproven and to mandate gradual weaning plans. Clinicians need to address misconceptions like the “chemical imbalance” theory, recognize withdrawal symptoms accurately, and offer non-drug approaches like psychological therapies for more durable benefits.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this psychopharmacology research news
Author: Jessica Stanley
Source: Adelaide University
Contact: Jessica Stanley – Adelaide University
Image: The image is credited to 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 Australians use antidepressants for longer periods, and for less severe conditions, than current guidelines recommend. Recent commentary has explored the rationale for stopping antidepressants, but overlooked flaws in the evidence for continuing antidepressants long- term.
Objective
To critically appraise the evidence for continuing antidepressants long-term (>12 months).
Discussion
The evidence for long-term use of antidepressants stems primarily from discontinuation studies in which people taking antidepressants are randomised to either stop or continue. These studies do not distinguish withdrawal symptoms from relapse. Worsening mood/anxiety in the discontinued group is interpreted as relapse and findings interpreted as evidence that long-term therapy prevents relapse, ignoring the possibility that the apparent benefits of continuing antidepressants might lie in suppressing withdrawal symptoms. Due to the lack of robust evidence for benefit, and established evidence showing harm with long-term use, antidepressant treatment should be regularly reviewed with shared decision making about whether to continue or stop.
