Alpha7 nAChR Agonists for Cognitive Deficit and Negative Symptoms in Schizophrenia: A Meta-analysis of Randomized Double-blind Controlled Trials

BACKGROUND: Previous clinical trials of α7-nicotinic acetylcholine receptor agonists (α7-nAChR agonists) showed mixed results in treating the cognitive and negative symptoms of schizophrenia. AIMS: To assess the efficacy and safety of α7-nAChR agonists in treating the cognitive and negative symptoms in schizophrenia. METHODS: A literature search was conducted to identify randomized double-blind placebo-controlled trials for schizophrenia published before May 26, 2017, by searching PubMed, Embase, ClinicalTrials.gov, the Cochrane Library and the Chinese language databases CNKI, Wanfang, and VIP Data. The effects of α7-nAChR agonists were evaluated for overall cognitive function and negative symptoms by calculating standard mean difference (SMDs) between active drugs and placebo added to antipsychotics. RESULTS: 8 studies with low bias were included. We found no statistically significant effects of α7 nAChR agonists on the overall cognitive function (SMD=-0.10[-0.46, 0.25], I(2) =88%) and negative symptoms (SMD=0.13 [-0.04, 0.30], I(2) =64%) in patients with schizophrenia. Sensitivity analysis showed these results to be firm. And this drug is generally safe and well tolerated with no significant difference from placebo based on adverse events (RR=1.02, [0.85, 1.23]) and dropouts (RR=1.04, [0.61, 1.78]) data. Evidence based on outcomes from the meta-analysis was rated as ‘moderate’ as per the GRADE guidelines. CONCLUSION: α7-nAChR agonists may not be effective in reversing overall cognitive impairments and negative symptoms in patients with schizophrenia as adjunctive therapies.