The Acetylcholinesterase inhibitors (Donepezil, Rivastigmine and Galantamine) have been studied in the cognitive deficit states like Alzheimer’s and others and have been in use for sometime. These new group of compounds are being tried in the treatment of schizophrenia; there are no existing systematic reviews of these groups of compounds.

We included all clinical randomised trials comparing acetylcholinesterase inhibitors with antipsychotics or placebo either alone or in combination for schizophrenia. The outcomes were grouped into the short term (up to 12 weeks), medium term (13–26 weeks) and long term (over 26 weeks). The Primary outcome was improvement in global state.

We were able to include 17 studies. The results showed mild benefit of antipsychotic/acetylcholinesterase inhibitors over placebo/antipsychotic in the following outcomes:

1. 1. Mental state: negative symptoms (2 RCTs, n = 31, MD −1.69 CI −2.80 to −0.57),) and general psychopathology (2 RCTs, n = 31, MD −3.86 CI −5.40 to −2.32), as measured on PANSS.

2. 2. One short term study showed improvement in depressive symptoms as measured by CDSS (Data skewed)

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

However, the validity of all results is challenged by the quality of the study design; especially, small duration of studies with small number of participants.