Systematic review and meta-analysis of the efficacy and safety of minocycline in schizophrenia.
Our aim was to perform an updated systematic review and meta-analysis on the efficacy and safety of adjunctive minocycline as a treatment of schizophrenia.



We conducted a PubMed/Scopus database search from inception to 3 February 2016 for randomized, placebo-controlled trials (RCTs), open non-randomized studies, and case reports/series evaluating minocycline in patients with schizophrenia. Random-effects meta-analysis of positive, negative, depressive, and cognitive symptom rating scales, discontinuation and adverse effects rates calculating standardized mean difference (SMD), and risk ratios±95% confidence intervals (CI 95%) were calculated.



Six RCTs were eligible (minocycline n=215, placebo n=198) that demonstrated minocycline's superiority versus placebo for reducing endpoint Positive and Negative Syndrome Scale (PANSS) total scores (SMD=-0.59; CI 95%=[1.15, -0.03]; p=0.04), negative (SMD=-0.76; CI 95%=[-1.21, -0.31]; p=0.001); general subscale scores (SMD=-0.44; CI 95%=[-0.88, -0.00]; p=0.05), Clinical Global Impressions scores (SMD=-0.50; CI 95%=[-0.78, -0.22]; p<0.001); and executive functioning (SMD=0.22; CI 95%=[0.01, 0.44]; p=0.04). Endpoint PANSS positive symptom scores (p=0.13), depression rating scale scores (p=0.43), attention (p=0.47), memory (p=0.52), and motor speed processing (p=0.50) did not significantly differ from placebo, before execution of a trim-and-fill procedure. Minocycline did not differ compared to placebo on all-cause discontinuation (p=0.56), discontinuation due to inefficacy (p=0.99), and intolerability (p=0.51), and due to death (p=0.32). Data from one open-label study (N=22) and three case series (N=6) were consistent with the metaanalytic results.



Minocycline appears to be an effective adjunctive treatment option in schizophrenia, improving multiple relevant disease dimensions. Moreover, minocycline has an acceptable safety and tolerability profile. However, more methodologically sound and larger RCTs remain necessary to confirm and extend these results.
1Department of Neurosciences,University of Padova,Padova,Italy.
Marco
0000-0003-4877-7233
M
Solmi
3Institute for Clinical Research and Education in Medicine (IREM),Padova,Italy.
Nicola
0000-0002-9328-289X
N
Veronese
5Kaski Sewa Hospital and Research Centre,Pokhara,Nepal.
Nita
N
Thapa
4Department of Medicine (DIMED), Geriatrics Section,University of Padova,Padova,Italy.
Silvia
S
Facchini
6Physiotherapy Department,South London and Maudsley NHS Foundation Trust,London,United Kingdom.
Brendon
B
Stubbs
8New York Psychiatric Institute,Columbia University,New York,New York,USA.
Michele
M
Fornaro
9Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine,Federal University of Ceará,Fortaleza,Ceará,Brazil.
André F
AF
Carvalho
10The Zucker Hillside Hospital,Psychiatry Research,Northwell Health,Glen Oaks,New York,USA.
Christoph U
CU
Correll
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008911:Minocycline / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D014150:Antipsychotic Agents; D008911:Minocycline
Minocycline; efficacy; meta-analysis; safety; schizophrenia; systematic review