title: Safety and tolerability of long-acting injectable versus oral antipsychotics: A meta-analysis of randomized controlled studies comparing the same antipsychotics.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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: Yamanashi Prefectural KITA Hospital, Yamanashi, Japan; The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA.
authors: Fuminari
authors: F
authors: Misawa
authors: 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.
authors: Taishiro
authors: T
authors: Kishimoto
authors: 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.
authors: Katsuhiko
authors: K
authors: Hagi
authors: 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.
authors: John M
authors: JM
authors: Kane
authors: 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.
authors: Christoph U
authors: CU
authors: Correll
mesh_terms: D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D003692:Delayed-Action Preparations; D006801:Humans; D007267:Injections; D016032:Randomized Controlled Trials as Topic
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations
keywords: Adverse events; Long-acting injectable antipsychotics; Meta-analysis; Oral antipsychotics; Randomized controlled trial; Schizophrenia