Add-on Therapy With Acetylcholinesterase Inhibitors for Memory Dysfunction in Schizophrenia

Abstract

Memory impairment is frequent in schizophrenia and remains difficult to treat. Improved memory function is associated with a better functional outcome. Some clinical trials have used add-on therapy with acetylcholinesterase inhibitors (AChEIs) to test the cognitive enhancement effect of this kind of medication, which is usually prescribed for other indications than schizophrenia. To perform a systematic review with meta-analysis. Studies were identified using electronic search engines, hand searches, cross-referencing of studies, and contacts with investigators. Eligible studies were those comparing cognitive performance in patients with schizophrenia before and after AChEI treatment, randomized controlled trials, and crossover and open trials of AChEI in people with schizophrenia, with trial duration of more than 2 weeks. Validated neurocognitive measures and computerized batteries were used to corroborate the effect. Our findings reveal a small to medium improvement in short-term memory and long-term memory (LTM) performance when patients are compared with the baseline performance, but when compared with controls (placebo treatment) at the end of the trial, they performed worse on both short-term memory and on LTM. However, the effects were nonsignificant. The LTM magnitude estimate demonstrating a treatment effect between the start and end points of the trial consisted of 8 studies (before treatment, n = 209; overall attrition rate, 8%). The effect estimate was significant and close to heterogeneous. Duration of trial increases the effect estimate slightly. The analysis was broken down by AChEI: 5 studies of donepezil (effect size [ES], -0.352), 2 studies of rivastigmine (ES, 0.383), and 1 study of galantamine. There were 6 studies of AChEI added to second-generation antipsychotics (ES, 0.424) and 2 studies of first-generation antipsychotics (ES, 0.207). Notwithstanding an extensive investigation, eligible data for the meta-analysis were nominal. To date, and overall, our quantitative systematic review provides no clear evidence on whether AChEIs should be prescribed for memory enhancement in patients with schizophrenia.