Cited by 250Treatment of Major DepressionPain Management and Placebo EffectPsychotherapy Techniques and Applications

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Is There a Delay in the Antidepressant Effect? A Meta-Analysis

Posternak, Michael A., Zimmerman, Mark·2005·The Journal of Clinical Psychiatry

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Abstract

Objectives It has long been thought that there is a delay of several weeks before a true antidepressant effect occurs, although this theory has increasingly come into question. The goals of this meta-analysis were to determine whether significant drug-placebo separation occurs during the first 2 weeks of treatment and to ascertain whether the timing of response to antidepressant medication and placebo is distinct. Data sources Seventy-six double-blind, placebo-controlled trials conducted between 1981 and 2000, included in a recently published meta-analysis that evaluated placebo response rates in depressed outpatients, were reviewed. In addition, each issue of 6 psychiatric journals from January 1992 through December 2001 was reviewed. Study selection Forty-seven studies that evaluated antidepressant medications with established efficacy, performed weekly or biweekly (every other week) evaluations, and presented the time course of improvement as measured by the Hamilton Rating Scale for Depression were included in our meta-analysis. Data synthesis The time course of improvement on active medication and placebo was nearly identical, as 60.2% and 61.6% of the improvement that occurred on active medication and placebo, respectively, took place during the first 2 weeks of treatment. Drug-placebo differences were not only present but were most pronounced during the first 2 weeks of treatment and diminished in a stepwise fashion thereafter. A series of subanalyses confirmed that th…

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Result
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Method
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Background
A Retrospective, Pilot Study of De Novo Antidepressant Medication Initiation in Intensive Care Unit Patients and Post-ICU Depression
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Background
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“…affect; adult; depression; ecological momentary assessment; actigraphy Evidence-based pharmacotherapy for major depressive disorder (MDD) is readily available, commonly employed and associated with a 60% improvement in symptoms during the first two weeks of therapy (Posternak & Zimmerman, 2005).”
Method
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“Whereas antidepressants can begin to work within 1–2 weeks in depression, 15 the onset of benefit for DGBI may take longer, especially in patients with long-standing symptoms.”
Rapid-Acting Treatments for Perinatal Depression: Clinical Landscapes and Future Horizons
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“Moreover, more than 80% of the improvement on placebo was noted to occur, on average, in the first half of the 6-week trial.(10) The growing interest in alternative and natural antidepressants has raised further questions about the placebo responseVfor example, ‘‘To what degree is the response to natural remedies due…”
Result
The efficacy of psychopharmacotherapy of late onset depression: the optimization of treatment duration
Ivanets, N. N., Kinkulkina, M. A., Avdeeva, T. I., Tikhonova, Y. G., & Lukyanova, A. V. (2016) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro20161164116-27 · Cited by 2
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“Data suggest that the timing and rate of improvements after initiation of an antidepressant can vary with some patients, demonstrating evidence of improvement within 1 week of treatment.(37,38) Treatment of depressive symptoms may not affect the overall disease trajectory in patients who are experiencing decline eithe…”
Background
Evidence-Based Korean Pharmacological Treatment Guideline for Depression, Revised Edition (II) : Antidepressant Efficacy Compared with Placebo, Difference in Efficacy of Antidepressants, and Appropriate Time of Efficacy Judgment in Antidepressant Therapy
Sung, S.-H., Park, S., Han, K., Won, E., Lee, H.-Y., Koo, J.-W., Paik, J., Lee, K., Jeon, H. J., Lee, M., et al. (2013) · 신경정신의학 · doi:10.4306/jknpa.2013.52.5.372 · Cited by 2
Suggested early onset of true action of antidepressant drugs may be artefactual: a heuristic study
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“Returning to the meta-analysis by Posternak and Zimmerman (2005), the percentage improvements of those assigned to the antidepressant drug and placebo groups, respectively, were 35 and 40% at week 1 and with almost equivalent additional weekly increases across the placebo and active drug groups…”
Method
The promise of rapidly acting antidepressants: challenges and opportunities.
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“20 Therefore, for many people newly starting antidepressants, the behaviour of taking antidepressants each day is unlikely to be reinforced via symptom relief in the first few weeks.”
Safety and efficacy of zuranolone in Japanese adults with major depressive disorder: An open‐label, repeated‐treatment part of a Phase 3 clinical trial
Kato, M., Nakagome, K., Baba, T., Sonoyama, T., Fukuju, H., Shimizu, R., Gomez, J. C., Motomiya, T., & Inoue, T. (2026) · Psychiatry and Clinical Neurosciences Reports · doi:10.1002/pcn5.70302 · Cited by 1
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CURRENT STATE OF PSILOCYBIN-ASSISTED THERAPY IN MOOD DISORDERS
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“Furthermore, if and when they do, the latency of effect associated with these treatments often requires a window of two to six weeks and/or induces undesirable effects, resulting in discontinuation of treatment (Carval - ho et al. 2016, Posternak & Zimmerman 2005).”
Heart rate variability during inpatient treatment of depression
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“We decided to use a three-week observation period, because about 70% of patients treated for depression show an initial treatment response within two to three weeks of respective inpatient care [26 – 30].”
Single I.V.-ketamine Augmentation of Newly Initiated Venlafaxine Hydrocortisone for Treatment-resistant Depression: Randomized, Double-blind Controlled Study ProtocolPreprint
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Authors: Posternak, M. A., & Zimmerman, M.
Affiliations: Brown University (US)
ORCID: Zimmerman, Mark
Venue: The Journal of Clinical Psychiatry
Publisher: Physicians Postgraduate Press, Inc
Published: 2005-02-15
Volume: 66
Issue: 02
Pages: 148-158
ISSN: 0160-6689 (ISSN-L)
DOI: 10.4088/jcp.v66n0201
OpenAlex: W2089202379
Cited by: 250
References: 0
Citations by year: 2026: 6 · 2025: 9 · 2024: 10 · 2023: 6 · 2022: 10 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 6 · 2017: 14 · 2016: 7 · 2015: 9 · 2014: 10 · 2013: 19 · 2012: 12
FWCI: 13.17
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Keywords: depression, Hamilton Depression Rating Scale
MeSH terms: Antidepressive Agents, Depressive Disorder, Double-Blind Method, Drug Administration Schedule, Humans, Placebos, Psychiatric Status Rating Scales, Time Factors, Cohort Studies, Placebo Effect, Randomized Controlled Trials as Topic, Treatment Outcome

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Is There a Delay in the Antidepressant Effect? A Meta-Analysis

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