title: Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder: protocol for a systematic review and meta-analysis.
abstract: BACKGROUND
  Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder.
  
  
  METHODS
  The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.
  
  
  BACKGROUND
  Ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentation and the press.
  
  
  BACKGROUND
  PROSPERO CRD42015023948.
authors.affiliation: Pharmacy Department, Norfolk and Suffolk NHS Foundation Trust, UK.
authors.forename: Asta R
authors.initials: AR
authors.lastname: Prajapati
authors.affiliation: Department of Research, Norfolk and Suffolk NHS Foundation Trust, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wilson
authors.affiliation: Department of Pharmacy, Aston University, UK.
authors.forename: Ian
authors.identifier: http://orcid.org/0000-0003-4152-9704
authors.initials: I
authors.lastname: Maidment
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002985:Clinical Protocols; D003625:Data Collection; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D011785:Quality Assurance, Health Care; D016032:Randomized Controlled Trials as Topic; D000078202:Systematic Reviews as Topic; D015201:Meta-Analysis as Topic
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations
keywords: Antipsychotic; Bipolar disorder; Depot preparation; Maintenance therapy; Second generation antipsychotics