The antidepressant standoff: why it continues and how to resolve it

Johan Ormel*, Philip Spinhoven, Ymkje Anna de Vries, Angélique O J Cramer, Greg J Siegle, Claudi L H Bockting, Steven D Hollon

*Corresponding author for this work

    Research output: Contribution to journalEditorialAcademicpeer-review

    7 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)177-186
    Number of pages10
    JournalPsychological Medicine
    Volume50
    Issue number2
    Early online date29-Nov-2019
    DOIs
    Publication statusPublished - Jan-2020

    Keywords

    • Antidepressants
    • long-term effects
    • major depressive disorder
    • psychotherapy
    • recurrence
    • relapse
    • MAJOR DEPRESSIVE DISORDER
    • SEROTONIN REUPTAKE INHIBITORS
    • LONG-TERM TREATMENT
    • COGNITIVE THERAPY
    • PRIMARY-CARE
    • UNIPOLAR DEPRESSION
    • RELAPSE PREVENTION
    • ADULT DEPRESSION
    • PLACEBO-RESPONSE
    • GENERAL-PRACTICE

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