Adjunctive minocycline for major mental disorders: A systematic review

Wei Zheng, Xiao-Min Zhu, Qing-E Zhang, Gen Cheng, Dong-Bin Cai, Jie He, Chee H. Ng, Gabor S. Ungvari, Xiao-Jiang Peng, Yu-Ping Ning, Yu-Tao Xiang

Research output: Contribution to journalReview article

Abstract

Objectives: This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD). Methods: A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95% confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias. Results: Sixteen RCTs (n=1357) on minocycline (50-300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: -0.45 (95%CI: -0.73, -0.16), p=0.002; I-2=77%], positive [SMD: -0.15 (95%CI: -0.28, -0.02), p=0.02; I-2=0%], negative [SMD: -0.62 (95%CI: -0.95, -0.28), p=0.0003; I-2=85%] and general psychopathology scores [SMD: -0.28 (95%CI: -0.53, -0.03), p=0.03; I-2=59%] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache (p=0.02, number-needed-to-harm=14, 95%CI=5-14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category. Conclusion: In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated. Review registration: PROSPERO: CRD42018102483

Original languageEnglish
Article number0269881119858286
Number of pages12
JournalJournal of Psychopharmacology
DOIs
Publication statusE-pub ahead of print - Jul 2019

Cite this

Zheng, W., Zhu, X-M., Zhang, Q-E., Cheng, G., Cai, D-B., He, J., ... Xiang, Y-T. (2019). Adjunctive minocycline for major mental disorders: A systematic review. Journal of Psychopharmacology, [0269881119858286]. https://doi.org/10.1177/0269881119858286
Zheng, Wei ; Zhu, Xiao-Min ; Zhang, Qing-E ; Cheng, Gen ; Cai, Dong-Bin ; He, Jie ; Ng, Chee H. ; Ungvari, Gabor S. ; Peng, Xiao-Jiang ; Ning, Yu-Ping ; Xiang, Yu-Tao. / Adjunctive minocycline for major mental disorders : A systematic review. In: Journal of Psychopharmacology. 2019.
@article{517e2fcf24f74779af326f2417bdf23f,
title = "Adjunctive minocycline for major mental disorders: A systematic review",
abstract = "Objectives: This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD). Methods: A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95{\%} confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias. Results: Sixteen RCTs (n=1357) on minocycline (50-300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: -0.45 (95{\%}CI: -0.73, -0.16), p=0.002; I-2=77{\%}], positive [SMD: -0.15 (95{\%}CI: -0.28, -0.02), p=0.02; I-2=0{\%}], negative [SMD: -0.62 (95{\%}CI: -0.95, -0.28), p=0.0003; I-2=85{\%}] and general psychopathology scores [SMD: -0.28 (95{\%}CI: -0.53, -0.03), p=0.03; I-2=59{\%}] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache (p=0.02, number-needed-to-harm=14, 95{\%}CI=5-14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category. Conclusion: In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated. Review registration: PROSPERO: CRD42018102483",
keywords = "Minocycline, schizophrenia, bipolar disorder, major depressive disorder, negative symptoms, meta-analysis, DOUBLE-BLIND, BIPOLAR DISORDER, NEGATIVE SYMPTOMS, OXIDATIVE STRESS, DEPRESSIVE SYMPTOMS, GLOBAL BURDEN, OPEN-LABEL, ADD-ON, SCHIZOPHRENIA, METAANALYSIS",
author = "Wei Zheng and Xiao-Min Zhu and Qing-E Zhang and Gen Cheng and Dong-Bin Cai and Jie He and Ng, {Chee H.} and Ungvari, {Gabor S.} and Xiao-Jiang Peng and Yu-Ping Ning and Yu-Tao Xiang",
year = "2019",
month = "7",
doi = "10.1177/0269881119858286",
language = "English",
journal = "Journal of Psychopharmacology",
issn = "0269-8811",
publisher = "SAGE Publications Ltd",

}

Zheng, W, Zhu, X-M, Zhang, Q-E, Cheng, G, Cai, D-B, He, J, Ng, CH, Ungvari, GS, Peng, X-J, Ning, Y-P & Xiang, Y-T 2019, 'Adjunctive minocycline for major mental disorders: A systematic review' Journal of Psychopharmacology. https://doi.org/10.1177/0269881119858286

Adjunctive minocycline for major mental disorders : A systematic review. / Zheng, Wei; Zhu, Xiao-Min; Zhang, Qing-E; Cheng, Gen; Cai, Dong-Bin; He, Jie; Ng, Chee H.; Ungvari, Gabor S.; Peng, Xiao-Jiang; Ning, Yu-Ping; Xiang, Yu-Tao.

In: Journal of Psychopharmacology, 07.2019.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Adjunctive minocycline for major mental disorders

T2 - A systematic review

AU - Zheng, Wei

AU - Zhu, Xiao-Min

AU - Zhang, Qing-E

AU - Cheng, Gen

AU - Cai, Dong-Bin

AU - He, Jie

AU - Ng, Chee H.

AU - Ungvari, Gabor S.

AU - Peng, Xiao-Jiang

AU - Ning, Yu-Ping

AU - Xiang, Yu-Tao

PY - 2019/7

Y1 - 2019/7

N2 - Objectives: This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD). Methods: A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95% confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias. Results: Sixteen RCTs (n=1357) on minocycline (50-300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: -0.45 (95%CI: -0.73, -0.16), p=0.002; I-2=77%], positive [SMD: -0.15 (95%CI: -0.28, -0.02), p=0.02; I-2=0%], negative [SMD: -0.62 (95%CI: -0.95, -0.28), p=0.0003; I-2=85%] and general psychopathology scores [SMD: -0.28 (95%CI: -0.53, -0.03), p=0.03; I-2=59%] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache (p=0.02, number-needed-to-harm=14, 95%CI=5-14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category. Conclusion: In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated. Review registration: PROSPERO: CRD42018102483

AB - Objectives: This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD). Methods: A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95% confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias. Results: Sixteen RCTs (n=1357) on minocycline (50-300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: -0.45 (95%CI: -0.73, -0.16), p=0.002; I-2=77%], positive [SMD: -0.15 (95%CI: -0.28, -0.02), p=0.02; I-2=0%], negative [SMD: -0.62 (95%CI: -0.95, -0.28), p=0.0003; I-2=85%] and general psychopathology scores [SMD: -0.28 (95%CI: -0.53, -0.03), p=0.03; I-2=59%] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache (p=0.02, number-needed-to-harm=14, 95%CI=5-14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category. Conclusion: In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated. Review registration: PROSPERO: CRD42018102483

KW - Minocycline

KW - schizophrenia

KW - bipolar disorder

KW - major depressive disorder

KW - negative symptoms

KW - meta-analysis

KW - DOUBLE-BLIND

KW - BIPOLAR DISORDER

KW - NEGATIVE SYMPTOMS

KW - OXIDATIVE STRESS

KW - DEPRESSIVE SYMPTOMS

KW - GLOBAL BURDEN

KW - OPEN-LABEL

KW - ADD-ON

KW - SCHIZOPHRENIA

KW - METAANALYSIS

U2 - 10.1177/0269881119858286

DO - 10.1177/0269881119858286

M3 - Review article

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

SN - 0269-8811

M1 - 0269881119858286

ER -