Fuminari Misawa1, Taishiro Kishimoto2, Katsuhiko Hagi3, John M Kane4, Christoph U Correll5. 1. Yamanashi Prefectural KITA Hospital, Yamanashi, Japan; The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA. 2. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Keio University School of Medicine, Tokyo, Japan; Hofstra Northwell School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA. 3. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Sumitomo Dainippon Pharma Co., Ltd., Medical Affairs, Tokyo, Japan. 4. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra Northwell School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. 5. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra Northwell School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: ccorrell@lij.edu.
Abstract
OBJECTIVE: We aimed to assess whether long-acting injectable antipsychotics (LAIs), which are initiated in a loading strategy or overlapping with oral antipsychotics (OAPs) and which cannot be stopped immediately, are associated with greater safety/tolerability issues than OAPs. METHOD: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing LAIs and OAPs, including only LAI-OAP pairs of the same OAP (allowing oral risperidone and paliperidone as comparators for either risperidone or paliperidone LAI). Primary outcome was treatment discontinuation due to adverse events. Secondary outcomes included serious adverse events, death, ≥1 adverse event and individual adverse event rates. RESULTS: Across 16 RCTs (n=4902, mean age=36.4years, males=65.8%, schizophrenia=99.1%) reporting on 119 adverse event outcomes, 55 (46.2%) adverse events were reported by ≥2 studies allowing a formal meta-analysis. Out of all 119 reported adverse events, LAIs and OAPs did not differ significantly regarding 115 (96.6%). LAIs were similar to OAPs regarding the frequency of treatment discontinuation due to adverse events, serious adverse events, all-cause death and death for reasons excluding accident or suicide. Compared to OAPs, LAIs were associated with significantly more akinesia, low-density lipoprotein cholesterol change and anxiety. Conversely, LAIs were associated with significantly lower prolactin change. CONCLUSION: LAIs and OAPs did not differ on all serious and >90% of individual adverse events. However, more studies focusing on adverse event frequencies, severity and time course associated with LAI vs OAP formulations of the same antipsychotic are needed. Additionally, adverse events data for LAIs after stopping overlapping oral antipsychotic treatment are needed.
OBJECTIVE: We aimed to assess whether long-acting injectable antipsychotics (LAIs), which are initiated in a loading strategy or overlapping with oral antipsychotics (OAPs) and which cannot be stopped immediately, are associated with greater safety/tolerability issues than OAPs. METHOD: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing LAIs and OAPs, including only LAI-OAP pairs of the same OAP (allowing oral risperidone and paliperidone as comparators for either risperidone or paliperidone LAI). Primary outcome was treatment discontinuation due to adverse events. Secondary outcomes included serious adverse events, death, ≥1 adverse event and individual adverse event rates. RESULTS: Across 16 RCTs (n=4902, mean age=36.4years, males=65.8%, schizophrenia=99.1%) reporting on 119 adverse event outcomes, 55 (46.2%) adverse events were reported by ≥2 studies allowing a formal meta-analysis. Out of all 119 reported adverse events, LAIs and OAPs did not differ significantly regarding 115 (96.6%). LAIs were similar to OAPs regarding the frequency of treatment discontinuation due to adverse events, serious adverse events, all-cause death and death for reasons excluding accident or suicide. Compared to OAPs, LAIs were associated with significantly more akinesia, low-density lipoprotein cholesterol change and anxiety. Conversely, LAIs were associated with significantly lower prolactin change. CONCLUSION: LAIs and OAPs did not differ on all serious and >90% of individual adverse events. However, more studies focusing on adverse event frequencies, severity and time course associated with LAI vs OAP formulations of the same antipsychotic are needed. Additionally, adverse events data for LAIs after stopping overlapping oral antipsychotic treatment are needed.
Authors: Luisa Peters; Amanda Krogmann; Laura von Hardenberg; Katja Bödeker; Viktor B Nöhles; Christoph U Correll Journal: Curr Psychiatry Rep Date: 2019-11-19 Impact factor: 5.285