Trajectories of Acute Antidepressant Efficacy: How Long to Wait for Response? A Systematic Review and Meta-Analysis of Long-Term, Placebo-Controlled Acute Treatment Trials
Abstract
BACKGROUND: In patients who are not responding to antidepressant pharmacotherapy, information regarding the future probability of response with the same treatment is scarce. Specifically, it is unclear at what point in time the probability to respond or remit ceases to increase, because few studies report data on response or remission at repeated time points beyond 4 or 8 weeks of treatment. Consequently, treatment recommendations in clinical practice guidelines differ widely. DATA SOURCES: We systematically searched MEDLINE, Embase, PsycINFO, and CENTRAL databases through March 2014 using generic terms for depressive or affective disorders, individual drug names, and placebo (Prospero Registration: CRD42014010105). STUDY SELECTION: We identified double-blind, randomized studies with continuous outcome reporting from 4 weeks up to at least 12 weeks that compared antidepressant monotherapy to placebo in adult patients suffering from acute depressive disorder. DATA EXTRACTION: Data extraction and synthesis followed Cochrane Collaboration guidelines. Primary outcome was response; secondary outcomes were remission and changes in rating scale scores in previously unresponsive patients, respectively. RESULTS: Of 6,043 articles screened, we selected 9 studies including 3,466 patients. Altogether, 21.6% (18.6%, 24.9%) of previously nonresponsive patients achieved response with ongoing antidepressant treatment between weeks 5 and 8, and 9.9% (7.5%, 12.7%), between weeks 9 and 12. Probability of response when taking placebo was 13.0% (9.9%, 16.5%) between weeks 5 and 8 and 2.4% (1.2%, 4.6%) between weeks 9 and 12. Differences in the probability of response between antidepressant and placebo translated into a number needed to treat of 11 after 4 weeks and 17 after 8 weeks. Heterogeneity was low to moderate, and results remained stable across subgroup and sensitivity analyses. CONCLUSIONS: In patients unresponsive to antidepressant pharmacotherapy, improvements in psychopathology can be expected with ongoing antidepressant treatment for up to 3 months. After 8 weeks of treatment, improvement with ongoing monotherapy is relatively small.
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A recently published review assessing results after 24 weeks showed that the longer-term effects of antidepressants (SMD 0.34) seem as small as the short-term effects.
“A recently published review assessing results after 24 weeks showed that the longer-term effects of antidepressants (SMD 0.34) seem as small as the short-term effects.”
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- Authors
- Henssler, J., Kurschus, M., Franklin, J., Bschor, T., & Baethge, C.
- Affiliations
- University of Cologne (DE)
- Schlosspark-Klinik (DE)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2018-06-27
- Volume
- 79
- Issue
- 3
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2795496390
- Cited by
- 44
- References
- 0
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 2
- FWCI
- 2.42
- 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
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Keywords
- antidepressant response, remission, placebo response, number needed to treat, antidepressant monotherapy
- MeSH terms
- Antidepressive Agents, Major Depressive Disorder, Humans, Randomized Controlled Trials as Topic, Outcome Assessment, Health Care, Depressive Disorder, Treatment-Resistant
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