Acetylcholinesterase inhibitors for schizophrenia

Evidence Summaries

Level of Evidence = D
Acetylcholinesterase inhibitors in combination with antipsychotics might possibly be effective on a few domains of mental state and cognition in patients with schizophrenia, although the evidence is insufficient.

A Cochrane review 1 included 17 studies with a total of 670 subjects. Nine trials included people with a sole diagnosis of schizophrenia, 7 studies with a diagnosis of schizophrenia or schizoaffective disorder and one study with no clear diagnostic criteria. The most commonly used acetylcholinesterase inhibitors were donepezil, rivastigmine and galantamine. The overall rate of participants leaving studies early was low (13.6 %) and showed no clear difference between the two groups. The primary outcome of interest was reported in only five studies. The acetylcholinesterase inhibitor plus antipsychotic showed benefit over antipsychotic and placebo in the following outcomes.

1. Mental state - PANSS negative symptoms average end point score (MD -1.69 95% CI -2.80 to -0.57; 2 RCTs, n = 31) and PANSS General Psychopathology average end point score (MD -3.86 95% CI -5.40 to -2.32; 2 RCTs, n = 31).

2. Cognitive domains - attention, (MD 1.20 95% CI 0.14 to 2.26; 1 RCT, n = 73), visual memory (MD 1.90 95% CI 0.52 to 3.28; 2 RCTs, n = 48), verbal memory and language (MD 3.46 95% CI 0.67 to 6.26; 3 RCTs, n = 42) and executive functioning (MD 17.10 95% CI 0.70 to 33.50; 1 RCT, n = 24).

3. Tolerability - EPSE: AIMS, (MD 1.50 95% CI 1.04 to 1.96; 1 RCT, n = 35).

No difference was noted between the two arms in other outcomes.

Comment: The quality of the evidence is downgraded by study quality (inadequate allocation concealment, lack of blinding, short follow-up), imprecise results (limited study size for each comparison) and indirectness of evidence (differences in studied outcomes).


1. Singh J, Kour K, Jayaram MB. Acetylcholinesterase inhibitors for schizophrenia. Cochrane Database Syst Rev 2012;1:CD007967.  [PMID:22258978]

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