Is there a delay in the antidepressant effect? A meta-analysis

Posternak, Michael A.; Zimmerman, Mark

doi:10.4088/jcp.v66n0201

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

Is there a delay in the antidepressant effect? A meta-analysis

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

DOI 10.4088/jcp.v66n0201

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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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Factors contributing to rapid improvement may include medication effects (e.g., antidepressant, antipsychotic agents), removal of alcohol and substances, and psychotherapy gains.
“Factors contributing to rapid improvement may include medication effects (e.g., antidepressant, antipsychotic agents) (Agid et al., 2003; Posternak and Zimmerman, 2005), removal of alcohol and substances, and psychotherapy gains (Stiles et al., 2003).”
From Time in treatment: Examining mental illness trajectories across inpatient psychiatric treatment (2020) · cites this paper as Posternak and Zimmerman, 2005

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Optimizing the management of depression: primary care experience
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Pharmacological management of unipolar depression
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Homeostatic cAMP regulation by the RGS7 complex controls depression-related behaviors
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“For the risk group of patients without improvement in the first two weeks of treatment, remission and response rates range between 4–14 and 11–19 percent (Henkel et al., 2009; Hennings et al., 2009; Katz et al., 2004; Nierenberg et al., 2000; Papakostas et al., 2006; Posternak and Zimmerman, 2005; Stassen et al., 2007…”
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The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder
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“Two meta-analyses revealed that antidepressant treatment response can take place early in the course of treatment 14,15 and two meta-analyses demonstrated that early improvement after the ﬁ rst 2 weeks of antidepressant treatment can predict subsequent treatment outcome with high sensitivity in…”
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Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: A randomized open-label trial
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“…meta-analyses show not only that antidepressants start to exert their antidepressant efficacy within a couple of weeks (Papakostas, et al., 2006; Posternak and Zimmerman, 2005; Taylor, et al., 2006), but also that early nonresponse to initial antidepressant treatment is a predictor for…”
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Timing of Clinical Improvement and Symptom Resolution in the Treatment of Major Depressive Disorder
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Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives
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“on typical antidepressant drugs also usually occur within the first two weeks of treatment (Posternak and Zimmerman, 2005).”
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Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: A pilot study
Rojas, P. S., Rosemarie Fritsch, M., Rojas, R., Jara, P., & Fiedler, J. L. (2011) · Psychiatry Research · doi:10.1016/j.psychres.2011.04.032 · Cited by 37 · see citing works
“, 1984), there is a large body of evidence suggesting that a true response to an antidepressant can be observed within the first 14 days of treatment (Nierenberg et al., 2000; Katz et al., 2004; Posternak and Zimmerman, 2005; Papakostas et al., 2006; Taylor et al., 2006; Stassen et al., 2007; Tadic et al., 2010a).”
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Modeling Trajectory of Depressive Symptoms Among Psychiatric Inpatients: A Latent Growth Curve Approach
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Background
Behavioural and computational methods reveal differential effects for how delayed and rapid onset antidepressants effect decision making in rats
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Early Prediction of Fluoxetine Response for Han Chinese Inpatients With Major Depressive Disorder
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Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with Major Depressive Disorder - the EMC trial
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Method
A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response.
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“=9.59, d.f.=1, p=0.002) than the 62.7 % rate reported in a recent meta-analysis of antidepressant trials ( Posternak and Zimmerman, 2005 ).”
ResultInfluentialSelf-citation
Causality of stem cell based neurogenesis and depression – To be or not to be, is that the question?
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“In addition, several meta-analyses found no evidence to supportDART, but rather suggest true antidepressant/antipsychotic effects to occur already within the first 1 to 2 weeks (Agid et al., 2003; Posternak and Zimmerman, 2005).”
Background
Early improvement as a predictor of eventual antidepressant treatment response in severely depressed inpatients
Vermeiden, M., Kamperman, A., Vulink, M. E., van den Broek, W. W., & Birkenhäger, T. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3765-1 · Cited by 28 · see citing works
“Three meta-analyses (Posternak and Zimmerman 2005; Papakostas et al. 2006; Taylor et al. 2006) concluded that antidepressant response can take place early in the course M.”
Background
Association of a functional polymorphism in the adrenomedullin gene (ADM) with response to paroxetine
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Time to response for duloxetine 60 mg once daily versus placebo in elderly patients with major depressive disorder
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BackgroundMethodResultInfluential
Efficacy and safety of zuranolone in Japanese adults with major depressive disorder: A double‐blind, randomized, placebo‐controlled, phase 2 clinical trial
Kato, M., Nakagome, K., Baba, T., Sonoyama, T., Okutsu, D., Yamanaka, H., Shimizu, R., Motomiya, T., & Inoue, T. (2023) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13569 · Cited by 28 · see citing works
“A metaanalysis of 76 double-blind, placebo-controlled trials shows that in general, the effect of antidepressant is slow.(6,39) Similarly, another meta-analysis of 28 placebo-controlled, randomized controlled trials (n = 5872) of SSRIs reported that the treatment response was greatest in the first week.”
Background

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 › 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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