ReviewTherapeutic advances in psychopharmacology2020
How effective are antidepressants for depression over the long term? A critical review of relapse prevention trials and the issue of withdrawal confounding.
Review in Therapeutic advances in psychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- A systematic review of manipulations to pharmaceutical dosage forms used in psychotropic tapering plans.British journal of clinical pharmacology · 2025Pooled it
- Influence of antidepressant use on periodontal status: a systematic review and meta-analysis.Clinical oral investigations · 2025Pooled it
- Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults.The Cochrane database of systematic reviews · 2021Pooled it
- Trial
- The discontinuation-emergent signs and symptoms (DESS) scale: reliable measurement-but perhaps not of antidepressant withdrawal.European archives of psychiatry and clinical neuroscience · 2026Article
- Are People Worse Off in a Mental Health Treatment Paradigm Where Medication Is Deemphasised? A Naturalistic Noninferiority Trial of an Initiative to Improve Patient Choice.The International journal of social psychiatry · 2026Article
- Feasibility and Tolerability ofAnnals of neurosciences · 2026Article
- Bridging reward and resilience: the endocannabinoid system as a unifying mechanism in exercise-induced protection against major depressive disorder.Frontiers in psychiatry · 2026Review
- Institutional Corruption in the Political Economy of Global Mental Health: Challenges for Transformative Human Rights Praxis.Health and human rights · 2025Article
- Testing the internal validity of the maintenance/discontinuation study design for antidepressant medications in depression using simulations.medRxiv : the preprint server for health sciences · 2025Article
- Antidepressant prescribing in Australian primary care: time to reevaluate.The Medical journal of Australia · 2025Article
- 11,12-Diacetyl-Carnosol Ameliorates Depression-Like Behaviors and Memory Dysfunction in CUMS Mouse Model via Inhibiting HMGB1-Mediated Neuroinflammation.CNS neuroscience & therapeutics · 2025Article
- [Can antidepressants negatively alter the long-term course of depressive disorders?]Der Nervenarzt · 2025Review
- The Iatrogenic Consequences of Medicalising Grief: Resetting the Research Agenda.Sociology of health & illness · 2025Article
- Article
- Psychotropic deprescribing across different prescribing professions in New Mexico and Louisiana.PLOS mental health · 2025Article
- Hidden Costs: The Clinical and Research Pitfalls of Mistaking Antidepressant Withdrawal for Relapse.Psychotherapy and psychosomatics · 2025Article
- Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications.Frontiers in cellular neuroscience · 2025Review
- From antidepressants and psychotherapy to oxytocin, vagus nerve stimulation, ketamine and psychedelics: how established and novel treatments can improve social functioning in major depression.Frontiers in psychiatry · 2024Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this article is to discuss the validity of relapse prevention trials and the issue of withdrawal confounding in these trials. Recommendations for long-term antidepressant treatment are based almost exclusively on discontinuation trials. In these relapse prevention trials, participants with remitted depression are randomised either to have the antidepressant abruptly discontinued and replaced by inert placebo or to continue active treatment. The drug-placebo difference in relapse rates at the end of the maintenance phase is then interpreted as a prophylactic drug effect. These trials consistently produce remarkable benefits for maintenance treatment. However, the internal validity of this trial protocol is compromised, as research has shown that abruptly stopping antidepressants can cause severe withdrawal reactions that lead to (or manifest as) depression relapses. That is, there is substantial withdrawal confounding in discontinuation trials, which renders their findings uninterpretable. It is not clear to what degree the drug-placebo separation in relapse prevention (discontinuation) trials is due to withdrawal reactions, but various estimations suggest that it is presumably the majority. A review of findings based on other methodologies, including real-world long-term effectiveness trials like STAR*D and various naturalistic cohort studies, do not indicate that antidepressants have considerable prophylactic effects. As absence of evidence does not imply evidence of absence, no definitive conclusions can be drawn from the literature. To enable a thorough risk-benefit evaluation, real-world effectiveness trials should not only focus on relapse prevention, but also assess antidepressants' long-term effects on social functioning and quality of life. Thus far, reliable long-term data on these outcome domains are lacking.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.