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Cited by 275Treatment of Major DepressionSchizophrenia research and treatmentElectroconvulsive Therapy Studies

The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.

Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes

Open access
Spielmans, Glen I., Berman, Margit I., Linardatos, Eftihia, Rosenlicht, Nicholas Z., Perry, Angela, Tsai, Alexander C.·2013·PLoS Medicine
DOI 10.1371/journal.pmed.1001403PMC PMC3595214
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Abstract

BACKGROUND: Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk-benefit profile is not well understood. We thus conducted a systematic review of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression. METHODS AND FINDINGS: We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole (odds ratio [OR], 2.01; 95% CI, 1.48-2.73), OFC (OR, 1.42; 95% CI, 1.01-2.0), quetiapine (OR, 1.79; 95% CI, 1.33-2.42), and risperidone (OR, 2.37; 95% CI, 1.31-4.30). The number needed to treat (NNT) was 19 for OFC and nine for each other drug. All drugs with the exception of OFC also had statistically significant effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58-2.72; NNT, 7), OFC (OR, 1.30, 95% CI, 0.87-1.93), quetiapine (OR, 1.53, 95% CI, 1.17-2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16-2.88; NNT, 8). All four drugs showed statistically significant effects on clinician-rated depression severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69 points on the Montgomery-Asberg Depression Rating Scale across drugs). On measures of functioning and quality of life, these medications produced either no benefit or a very small benefit, except for risperidone, which had a small-to-moderate effect on quality of life (g = 0.49). Treatment was linked to several adverse events, including akathisia (aripiprazole), sedation (quetiapine, OFC, and aripiprazole), abnormal metabolic laboratory results (quetiapine and OFC), and weight gain (all four drugs, especially OFC). Shortcomings in study design and data reporting, as well as use of post hoc analyses, may have inflated the apparent benefits of treatment and reduced the apparent incidence of adverse events. CONCLUSIONS: Atypical antipsychotic medications for the adjunctive treatment of depression are efficacious in reducing observer-rated depressive symptoms, but clinicians should interpret these findings cautiously in light of (1) the small-to-moderate-sized benefits, (2) the lack of benefit with regards to quality of life or functional impairment, and (3) the abundant evidence of potential treatment-related harm. Please see later in the article for the Editors' Summary.

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Crossref · 10.1371/journal.pmed.1001403

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Figure 1 Flowchart of published studies examined for inclusion in meta-analysis. MDD, major depressive disorder; RCT, randomized controlled trial.
Figure 1 Flowchart of published studies examined for inclusion in meta-analysis. MDD, major depressive disorder; RCT, randomized controlled trial.CC BY · PubMed Central
Figure 2 Remission rates by drug and overall.
Figure 2 Remission rates by drug and overall.CC BY · PubMed Central
Figure 3 Response rates by drug and overall.
Figure 3 Response rates by drug and overall.CC BY · PubMed Central
Figure 4 Funnel plot of trim and fill analysis. Open circles represent published studies; filled circles represent imputed unpublished studies. The overall effect size changes from 0.34 to 0.32 when including these imputed trials.
Figure 4 Funnel plot of trim and fill analysis. Open circles represent published studies; filled circles represent imputed unpublished studies. The overall effect size changes from 0.34 to 0.32 when including these imputed trials.CC BY · PubMed Central

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Research works printed but not linked: 4

  1. E Sigal, 2009, Bristol-Myers Squibb Company Q1 2009 earnings call transcript, Seeking Alpha
  2. D Healy, 2000, The assessment of outcomes in depression: measures of social functioning, Rev Contemp Pharmacother, 11, 295
  3. Hedges LV, Olkin I (1985) Statistical methods for meta-analysis. San Diego: Academic Press.
  4. Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edition. Hillsdale (New Jersey): Erlbaum.

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Metadata

Authors
Spielmans, G. I., Berman, M. I., Linardatos, E., Rosenlicht, N. Z., Perry, A., & Tsai, A. C.
Affiliations
  • Metropolitan State University (US)
  • San Francisco VA Medical Center (US)
  • Harvard University (US)
Corresponding author
Spielmans, Glen I.
ORCID
Venue
PLoS Medicine
Publisher
Public Library of Science (PLoS)
Published
2013-03-12
Volume
10
Issue
3
Pages
e1001403
ISSN
  • 1549-1277 (ISSN-L)
  • 1549-1676
DOI
10.1371/journal.pmed.1001403
PMC
PMC3595214
OpenAlex
W2340538438
Cited by
275
References
84
Citations by year
2026: 11 · 2025: 14 · 2024: 16 · 2023: 21 · 2022: 15 · 2021: 17 · 2020: 21 · 2019: 20 · 2018: 16 · 2017: 30 · 2016: 36 · 2015: 26 · 2014: 19 · 2013: 13
FWCI
3.93
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Veterans Affairs
  • National Institute of Mental Health (MH096620, K23MH096620)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords
adjunctive antipsychotic therapy, treatment-resistant depression, major depressive disorder, aripiprazole, olanzapine-fluoxetine combination, quetiapine, risperidone, remission, response rate, quality of life, adverse drug reactions, risk-benefit profile, antipsychotic safety, number needed to treat
MeSH terms
Depression, Major Depressive Disorder, Humans, Quality of Life, Antipsychotic Agents, Treatment Outcome, Publication Bias

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