title: Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions.
abstract: BACKGROUND
  Acetylcholinesterase inhibitors (AceI) and memantine might prove useful in bipolar disorder (BD) given their neuroprotective and pro-cognitive effects, as highlighted by several case reports. We aimed to systematically review the efficacy and safety of AceI and memantine across multiple outcome dimensions in BD.
  
  
  METHODS
  Systematic PubMed and SCOPUS search until 04/17/2015 without language restrictions. Included were randomized controlled trials (RCTs), open label studies and case series of AceI or memantine in BD patients reporting quantitative data on depression, mania, psychotic symptoms, global functioning, or cognitive performance. We summarized results using a best-evidence based synthesis.
  
  
  RESULTS
  Out of 214 hits, 12 studies (RCTs=5, other designs=7, total n=422) were included. Donepezil (studies=5; treated=102 vs. placebo=21): there was strong evidence for no effect on mania and psychotic symptoms; low evidence indicating no effect on depression. Galantamine (studies=3; treated=21 vs. controls=20) (placebo=10, healthy subjects=10): there was strong evidence for no effect on mania; moderate evidence for no effect on depression; low evidence for no effect on global functioning. Memantine (studies=4; treated=152 vs. placebo=88): there was conflicting evidence regarding efficacy for mania, depression and global functioning.
  
  
  CONCLUSIONS
  Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics.
  
  
  CONCLUSIONS
  There is limited but converging evidence of no effect of AceI in BD, and conflicting evidence about memantine in BD. Too few studies of mostly medium/low quality and lacking sufficient numbers of patients in specific mood states, especially mania, contributed data, focusing solely on short-term/medium-term treatment, necessitating additional high-quality research to yield more definite results.
authors.affiliation: Department of Medicine, DIMED, Geriatrics Division, University of Padova, Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy; National Health Care System, Padua Local Unit ULSS 17, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy; Surgical Pathology Unit, Santa Chiara Hospital, Trento, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchini
authors.affiliation: Institute of Behavioral Medicine, Department of Psychiatry, College of Medicine & Hospital, National Cheng-Kung University, Tainan, Taiwan, ROC.
authors.forename: Ru-Band
authors.initials: RB
authors.lastname: Lu
authors.affiliation: Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, United Kingdom; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: Department of Biomedical and Neuro-Motor Sciences, University of Bologna, Italy; Department of Mental Health, Local Sanitary, Unit n. 16 - ULSS 16, Padova, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Zaninotto
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, 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@nshs.edu.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology*; D016022:Case-Control Studies; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003863:Depression / Q000188:drug therapy; D003866:Depressive Disorder / Q000188:drug therapy; D000077265:Donepezil; D019317:Evidence-Based Medicine; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005702:Galantamine / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D008559:Memantine
keywords: Acetylcholinesterase inhibitors; Bipolar disorder; Depression; Mania; Memantine; Psychosis.