Marco Solmi1, Nicola Veronese2, Nita Thapa3, Silvia Facchini4, Brendon Stubbs5, Michele Fornaro6, André F Carvalho7, Christoph U Correll8. 1. 1Department of Neurosciences,University of Padova,Padova,Italy. 2. 3Institute for Clinical Research and Education in Medicine (IREM),Padova,Italy. 3. 5Kaski Sewa Hospital and Research Centre,Pokhara,Nepal. 4. 4Department of Medicine (DIMED), Geriatrics Section,University of Padova,Padova,Italy. 5. 6Physiotherapy Department,South London and Maudsley NHS Foundation Trust,London,United Kingdom. 6. 8New York Psychiatric Institute,Columbia University,New York,New York,USA. 7. 9Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine,Federal University of Ceará,Fortaleza,Ceará,Brazil. 8. 10The Zucker Hillside Hospital,Psychiatry Research,Northwell Health,Glen Oaks,New York,USA.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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.
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