Oral cholinesterase inhibitor add-on therapy for cognitive enhancement in schizophrenia: a quantitative systematic review, Part I

Cognitive impairment in schizophrenia is associated with outcomes affecting social function and vocational performance. Cognitive enhancement is thus recognized as fundamental in the treatment of schizophrenia. Some clinical trials have used acetylcholinesterase inhibitors (AChEIs) add-on therapy to test the cognitive-enhancing effects of these kinds of medication, which is usually prescribed for indications other than schizophrenia.

To perform a quantitative systematic review of the effects of AChEI on various cognitive domains (attention, language, and motor and executive functions) in schizophrenia.

Exhaustive electronic search engines, hand searches, cross-referencing of studies, and contacts with investigators were carried out.

The studies included compared neurocognitive performance in patients with schizophrenia before and after AChEI treatment in randomized controlled trials and crossover and open trials of AChEI in people with schizophrenia.

Our findings reveal a small, but significant, homogeneous effect estimate of AChEI on attention before and after treatment. A small nonsignificant heterogeneous effect estimate was yielded for motor performance after AChEI treatment. However, no significant change appears in language performance or executive functions after AChEI treatment, independently of the type of AChEI. After AChEI treatment, when patients were compared with control groups, no difference appears in attention and executive functions. Nevertheless, the analysis reveals that the control groups performed better on language tasks than patients after AChEI treatment but worse on motor tasks.

Despite an extensive investigation of the electronic and gray literature, few data appropriate for the meta-analysis were found. The results reveal a small improvement in attention and a trend on motor tasks after AChEI medication in schizophrenia. No clear conclusion can yet be reached concerning the cognitive-enhancing effects of AChEI considering the small number of studies available. This finding needs to be substantiated by larger trials. This systematic review complements a meta-analysis focusing on memory, which showed a small improvement with a cocktail of antipsychotics and AChEIs.