Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions

Nicola Veronese, Marco Solmi, Claudio Luchini, Ru Band Lu, Brendon Stubbs, Leonardo Zaninotto, Christoph U. Correll

Research output: Contribution to journalReview article

6 Citations (Scopus)

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. Limitations Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics. Conclusion 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.

Original languageEnglish
Pages (from-to)268-280
Number of pages13
JournalJournal of Affective Disorders
Volume197
DOIs
Publication statusPublished - 2016 Jun 1

Fingerprint

Memantine
Cholinesterase Inhibitors
Bipolar Disorder
Safety
Depression
Randomized Controlled Trials
Placebos
Galantamine
PubMed
Sample Size
Healthy Volunteers
Research Design
Language

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Veronese, Nicola ; Solmi, Marco ; Luchini, Claudio ; Lu, Ru Band ; Stubbs, Brendon ; Zaninotto, Leonardo ; Correll, Christoph U. / Acetylcholinesterase inhibitors and memantine in bipolar disorder : A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions. In: Journal of Affective Disorders. 2016 ; Vol. 197. pp. 268-280.
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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. Limitations Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics. Conclusion 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.",
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Acetylcholinesterase inhibitors and memantine in bipolar disorder : A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions. / Veronese, Nicola; Solmi, Marco; Luchini, Claudio; Lu, Ru Band; Stubbs, Brendon; Zaninotto, Leonardo; Correll, Christoph U.

In: Journal of Affective Disorders, Vol. 197, 01.06.2016, p. 268-280.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Acetylcholinesterase inhibitors and memantine in bipolar disorder

T2 - A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions

AU - Veronese, Nicola

AU - Solmi, Marco

AU - Luchini, Claudio

AU - Lu, Ru Band

AU - Stubbs, Brendon

AU - Zaninotto, Leonardo

AU - Correll, Christoph U.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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. Limitations Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics. Conclusion 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.

AB - 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. Limitations Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics. Conclusion 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.

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