Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: A systematic review and meta-analysis of randomized-controlled trials |
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| Affiliation: | 1. The National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) & Peking University Institute of Mental Health & The Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China;2. The National Clinical Research Center for Mental Disorders (Beijing Anding Hospital) & Department of Psychiatry, Capital Medical University & Center of Depression, Beijing Institute for Brain Disorders, China;3. Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macau SAR, China;4. Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA;5. School of Psychiatry & Clinical Neuroscience, University of Western Australia, Perth, Australia;6. Department of Psychiatry, Chinese University of Hong Kong, Hong Kong, China;7. Psychiatric Hospital, Guangzhou, China;8. Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, China;9. The First Hospital of Shanxi Medical University, Shanxi Province, China;10. West China Hospital, Sichuan University, China;11. Neuropsychiatric Hospital, Jilin, China;12. Mental Health Center, Xi-an, China;13. Jiangxi Psychiatric Hospital, Jiangxi, China;14. Suzhou Guangji Hospital, Suzhou, China;15. Hebei Mental Health Center, Hebei, China;1. Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada;2. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada;3. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada;4. Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada;5. Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada;6. Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan |
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| Abstract: | Limited options are available for clozapine-resistant schizophrenia and intolerable side effects of clozapine. We conducted a systematic review of randomized-controlled trials (RCTs) to determine the efficacy and safety of aripiprazole augmentation of clozapine for schizophrenia. Electronic databases searched included PubMed, Scopus, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. This review synthesized the data of four short-term (8–24 weeks), placebo-controlled trials (N = 347). The overall relative risk (RR, 95% confidence interval) of discontinuation rates was not significantly different between groups (RR = 1.41, 95% CI = 0.78 to 2.56). The pooled standardized mean differences (SMDs, 95% CIs) (Z-test; number of study; I2-index) suggested trends of aripiprazole augmentation benefits on overall psychotic [−0.40 (−0.87 to 0.07) (n = 3; Z = 1.68, p = 0.09; I2 = 68%)], positive [−1.05 (−2.39 to 0.29) (n = 3; Z = 1.54, p = 0.12; I2 = 94%)], and negative [−0.36 (−0.77 to 0.05) (n = 3; Z = 1.74, p = 0.08; I2 = 54%)] symptoms. Despite of no benefit on three cardiometabolic indices (i.e., fasting plasma glucose, triglyceride, and high-density lipoprotein), aripiprazole augmentation was superior for weight change with a mean difference (95% CI) of −1.36 kg (−2.35 to −0.36) (n = 3; Z = 2.67, p = 0.008; I2 = 39%) and LDL-cholesterol with a mean difference of −11.06 mg/dL (−18.25 to −3.87) (n = 3; Z = 3.02, p = 0.003; I2 = 31%). Aripiprazole augmentation was not correlated with headache and insomnia but significantly associated with agitation/akathesia (RR = 7.59, 95% CI = 1.43 to 40.18) (n = 3; Z = 2.38, p = 0.02; I2 = 0%) and anxiety (RR = 2.70, 95% CI = 1.02 to 7.15) (n = 1; Z = 2.00, p = 0.05). The limited short-term data suggested that aripiprazole augmentation of clozapine can minimize the cardiometabolic risk, causes agitation/akathesia, and may be effective in attenuating psychotic symptoms. |
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| Keywords: | Aripiprazole Drug augmentation Clozapine Schizophrenia Metabolic syndrome Adverse effects |
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