The antidepressant standoff: Why it continues and how to resolve it
Open accessAbstract
Background: Antidepressant medications (ADMs) are widely used and long-term use is increasing. Given this extensive use and recommendation of ADMs in guidelines, one would expect ADMs to be universally considered effective. Surprisingly, that is not the case; fierce debate on their benefits and harms continues. This editorial seeks to understand why the controversy continues and how consensus can be achieved. Methods: ‘Position’ paper. Critical analysis and synthesis of relevant literature. Results: Advocates point at ADMs impressive effect size (number needed to treat, NNT = 6–8) in acute phase treatment and continuation/maintenance ADM treatment prevention relapse/recurrence in acute phase ADM responders (NNT = 3–4). Critics point at the limited clinically significant surplus value of ADMs relative to placebo and argue that effectiveness is overstated. We identified multiple factors that fuel the controversy: certainty of evidence is low to moderate; modest efficacy on top of strong placebo effects allows critics to focus on small net efficacy and advocates on large gross efficacy; ADM withdrawal symptoms masquerade as relapse/recurrence; lack of association between ADM treatment and long-term outcome in observational databases. Similar problems affect psychological treatments as well, but less so. We recommend four approaches to resolve the controversy: (1) placebo-controlled trials with relevant long-term outcome assessments, (2) inventive analyses of observational databases, (3) patient cohort studies including effect moderators to improve personalized treatment, and (4) psychological treatments as universal first-line treatment step. Conclusions: Given the public health significance of depression and increased long-term ADM usage, new approaches are needed to resolve the controversy.
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Given the long-term effects, side effects, and costs of medications, the trend toward medication-only treatment is difficult to defend empirically.
“When we consider the long-term effects, side effects, and costs of medications, these trends are difficult to defend empirically (Antonuccio, Thomas, & Danton, 1997; Ormel et al., 2020).”
From A process-based approach to psychological diagnosis and treatment:The conceptual and treatment utility of an extended evolutionary meta model (2020) · cites this paper as Ormel et al., 2020
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Deadly Medicines and Organised Crime
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The antidepressant debate continues
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The antidepressant debate continues - Reply
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[The care standard 'Depressive disorders'].
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Self-citationDe zorgstandaard Depressieve stoornissen
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Self-citation
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- Authors
- Ormel, J., Spinhoven, P., de Vries, Y. A., Cramer, A. O. J., Siegle, G. J., Bockting, C. L. H., & Hollon, S. D.
- Affiliations
- Royal Netherlands Academy of Arts and Sciences (NL)
- Leiden University (NL)
- University of Pittsburgh (US)
- Vanderbilt University (US)
- Corresponding author
- Ormel, Johan
- ORCID
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2019-11-29
- Volume
- 50
- Issue
- 2
- Pages
- 177-186
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2991358494
- Cited by
- 22
- References
- 105
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 2 · 2020: 7
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- antidepressants, depression, antidepressant efficacy, placebo response, relapse prevention, long-term outcomes, antidepressant withdrawal symptoms, psychological intervention, quality of evidence, number needed to treat
- MeSH terms
- Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Humans, Long-Term Care, Psychotherapy, Recurrence, Randomized Controlled Trials as Topic, Secondary Prevention
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