Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials

Masahiro Nitta, Taishiro Kishimoto, Norbert Müller, Mark Weiser, Michael Davidson, John M. Kane, Christoph U. Correll

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Objective: To meta-analytically assess the efficacy and tolerability of nonsteroidal anti-inflammatory drugs (NSAIDs) vs placebo in schizophrenia. Method: Searching PubMed, PsycINFO, ISI Web of Science, and the US National Institute of Mental Health clinical trials registry from database inception to December 31, 2012, we conducted a systematic review/meta-analysis of randomized placebo-controlled studies assessing the efficacy of adjunctive NSAIDs. Primary outcome was the change in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes included change in PANSS positive and negative subscores, all-cause discontinuation, and tolerability outcomes. Random effects, pooled, standardized mean changes (Hedges' g) and risk ratios were calculated. Results: Across 8 studies, including 3 unpublished reports (n = 774), the mean effect size for PANSS total score was -0.236 (95% CI: -0.484 to 0.012, P =. 063, I2 = 60.6%), showing only trend-level superiority for NSAIDs over placebo. The mean effect sizes for the PANSS positive and negative scores were -0.189 (95% CI: -0.373 to -0.005, P =. 044) and -0.026 (95% CI: -0.169 to 0.117, P =. 72), respectively. The relative risk for all-cause discontinuation was 1.13 (95% CI: 0.794 to 1.599, P =. 503). Significant superiority of NSAIDs over placebo regarding PANSS total scores was moderated by aspirin treatment (N = 2, P =. 017), inpatient status (N = 4, P =. 029), first-episode status (N = 2, P =. 048), and (in meta-regression analyses) lower PANSS negative subscores (N = 6, P =. 026). Interpretation: These results indicate that adjunctive NSAIDs for schizophrenia may not benefit patients treated with first-line antipsychotics judged by PANSS total score change. NSAIDs may have benefits for positive symptoms, but the effect was minimal/small. However, due to a limited database, further controlled studies are needed, especially in first-episode patients.

Original languageEnglish
Pages (from-to)1230-1241
Number of pages12
JournalSchizophrenia Bulletin
Volume39
Issue number6
DOIs
Publication statusPublished - 2013 Nov

Fingerprint

Schizophrenia
Anti-Inflammatory Agents
Randomized Controlled Trials
Pharmaceutical Preparations
Placebos
Meta-Analysis
Databases
National Institute of Mental Health (U.S.)
PubMed
Antipsychotic Agents
Aspirin
Registries
Inpatients
Odds Ratio
Regression Analysis
Clinical Trials

Keywords

  • Augmentation
  • Concomitant
  • Inflammation
  • Nonsteroidal anti-inflammatory
  • Schizophrenia
  • Treatment resistance

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia : A meta-analytic investigation of randomized controlled trials. / Nitta, Masahiro; Kishimoto, Taishiro; Müller, Norbert; Weiser, Mark; Davidson, Michael; Kane, John M.; Correll, Christoph U.

In: Schizophrenia Bulletin, Vol. 39, No. 6, 11.2013, p. 1230-1241.

Research output: Contribution to journalArticle

Nitta, Masahiro ; Kishimoto, Taishiro ; Müller, Norbert ; Weiser, Mark ; Davidson, Michael ; Kane, John M. ; Correll, Christoph U. / Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia : A meta-analytic investigation of randomized controlled trials. In: Schizophrenia Bulletin. 2013 ; Vol. 39, No. 6. pp. 1230-1241.
@article{7e86aec95da94807b70285f08a37aa8a,
title = "Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials",
abstract = "Objective: To meta-analytically assess the efficacy and tolerability of nonsteroidal anti-inflammatory drugs (NSAIDs) vs placebo in schizophrenia. Method: Searching PubMed, PsycINFO, ISI Web of Science, and the US National Institute of Mental Health clinical trials registry from database inception to December 31, 2012, we conducted a systematic review/meta-analysis of randomized placebo-controlled studies assessing the efficacy of adjunctive NSAIDs. Primary outcome was the change in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes included change in PANSS positive and negative subscores, all-cause discontinuation, and tolerability outcomes. Random effects, pooled, standardized mean changes (Hedges' g) and risk ratios were calculated. Results: Across 8 studies, including 3 unpublished reports (n = 774), the mean effect size for PANSS total score was -0.236 (95{\%} CI: -0.484 to 0.012, P =. 063, I2 = 60.6{\%}), showing only trend-level superiority for NSAIDs over placebo. The mean effect sizes for the PANSS positive and negative scores were -0.189 (95{\%} CI: -0.373 to -0.005, P =. 044) and -0.026 (95{\%} CI: -0.169 to 0.117, P =. 72), respectively. The relative risk for all-cause discontinuation was 1.13 (95{\%} CI: 0.794 to 1.599, P =. 503). Significant superiority of NSAIDs over placebo regarding PANSS total scores was moderated by aspirin treatment (N = 2, P =. 017), inpatient status (N = 4, P =. 029), first-episode status (N = 2, P =. 048), and (in meta-regression analyses) lower PANSS negative subscores (N = 6, P =. 026). Interpretation: These results indicate that adjunctive NSAIDs for schizophrenia may not benefit patients treated with first-line antipsychotics judged by PANSS total score change. NSAIDs may have benefits for positive symptoms, but the effect was minimal/small. However, due to a limited database, further controlled studies are needed, especially in first-episode patients.",
keywords = "Augmentation, Concomitant, Inflammation, Nonsteroidal anti-inflammatory, Schizophrenia, Treatment resistance",
author = "Masahiro Nitta and Taishiro Kishimoto and Norbert M{\"u}ller and Mark Weiser and Michael Davidson and Kane, {John M.} and Correll, {Christoph U.}",
year = "2013",
month = "11",
doi = "10.1093/schbul/sbt070",
language = "English",
volume = "39",
pages = "1230--1241",
journal = "Schizophrenia Bulletin",
issn = "0586-7614",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia

T2 - A meta-analytic investigation of randomized controlled trials

AU - Nitta, Masahiro

AU - Kishimoto, Taishiro

AU - Müller, Norbert

AU - Weiser, Mark

AU - Davidson, Michael

AU - Kane, John M.

AU - Correll, Christoph U.

PY - 2013/11

Y1 - 2013/11

N2 - Objective: To meta-analytically assess the efficacy and tolerability of nonsteroidal anti-inflammatory drugs (NSAIDs) vs placebo in schizophrenia. Method: Searching PubMed, PsycINFO, ISI Web of Science, and the US National Institute of Mental Health clinical trials registry from database inception to December 31, 2012, we conducted a systematic review/meta-analysis of randomized placebo-controlled studies assessing the efficacy of adjunctive NSAIDs. Primary outcome was the change in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes included change in PANSS positive and negative subscores, all-cause discontinuation, and tolerability outcomes. Random effects, pooled, standardized mean changes (Hedges' g) and risk ratios were calculated. Results: Across 8 studies, including 3 unpublished reports (n = 774), the mean effect size for PANSS total score was -0.236 (95% CI: -0.484 to 0.012, P =. 063, I2 = 60.6%), showing only trend-level superiority for NSAIDs over placebo. The mean effect sizes for the PANSS positive and negative scores were -0.189 (95% CI: -0.373 to -0.005, P =. 044) and -0.026 (95% CI: -0.169 to 0.117, P =. 72), respectively. The relative risk for all-cause discontinuation was 1.13 (95% CI: 0.794 to 1.599, P =. 503). Significant superiority of NSAIDs over placebo regarding PANSS total scores was moderated by aspirin treatment (N = 2, P =. 017), inpatient status (N = 4, P =. 029), first-episode status (N = 2, P =. 048), and (in meta-regression analyses) lower PANSS negative subscores (N = 6, P =. 026). Interpretation: These results indicate that adjunctive NSAIDs for schizophrenia may not benefit patients treated with first-line antipsychotics judged by PANSS total score change. NSAIDs may have benefits for positive symptoms, but the effect was minimal/small. However, due to a limited database, further controlled studies are needed, especially in first-episode patients.

AB - Objective: To meta-analytically assess the efficacy and tolerability of nonsteroidal anti-inflammatory drugs (NSAIDs) vs placebo in schizophrenia. Method: Searching PubMed, PsycINFO, ISI Web of Science, and the US National Institute of Mental Health clinical trials registry from database inception to December 31, 2012, we conducted a systematic review/meta-analysis of randomized placebo-controlled studies assessing the efficacy of adjunctive NSAIDs. Primary outcome was the change in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes included change in PANSS positive and negative subscores, all-cause discontinuation, and tolerability outcomes. Random effects, pooled, standardized mean changes (Hedges' g) and risk ratios were calculated. Results: Across 8 studies, including 3 unpublished reports (n = 774), the mean effect size for PANSS total score was -0.236 (95% CI: -0.484 to 0.012, P =. 063, I2 = 60.6%), showing only trend-level superiority for NSAIDs over placebo. The mean effect sizes for the PANSS positive and negative scores were -0.189 (95% CI: -0.373 to -0.005, P =. 044) and -0.026 (95% CI: -0.169 to 0.117, P =. 72), respectively. The relative risk for all-cause discontinuation was 1.13 (95% CI: 0.794 to 1.599, P =. 503). Significant superiority of NSAIDs over placebo regarding PANSS total scores was moderated by aspirin treatment (N = 2, P =. 017), inpatient status (N = 4, P =. 029), first-episode status (N = 2, P =. 048), and (in meta-regression analyses) lower PANSS negative subscores (N = 6, P =. 026). Interpretation: These results indicate that adjunctive NSAIDs for schizophrenia may not benefit patients treated with first-line antipsychotics judged by PANSS total score change. NSAIDs may have benefits for positive symptoms, but the effect was minimal/small. However, due to a limited database, further controlled studies are needed, especially in first-episode patients.

KW - Augmentation

KW - Concomitant

KW - Inflammation

KW - Nonsteroidal anti-inflammatory

KW - Schizophrenia

KW - Treatment resistance

UR - http://www.scopus.com/inward/record.url?scp=84885194908&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885194908&partnerID=8YFLogxK

U2 - 10.1093/schbul/sbt070

DO - 10.1093/schbul/sbt070

M3 - Article

C2 - 23720576

AN - SCOPUS:84885194908

VL - 39

SP - 1230

EP - 1241

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

SN - 0586-7614

IS - 6

ER -