Galantamine augmentation of long-acting injectable risperidone for cognitive impairments in chronic schizophrenia

Galantamine, a reversible cholinesterase inhibitor with effects on nicotinic receptors, has shown mixed effects on cognitive impairments in patients with schizophrenia. Given these mixed results we examined whether galantamine compared to adjunctive placebo may improve cognitive functions in patients treated concomitantly with a long acting atypical antipsychotic.

The parent study was a 52-week double-blind, randomized study of treatment with long-acting injectable risperidone 25mg or 50mg every two weeks. Adjunctive galantamine or placebo treatment was administered from Month 6 to 12. Outcome measures were neurocognitive, psychopathology, social and quality of life functions. Patients were randomized to blinded galantamine up to 24mg/day or matching placebo tablets. All patients were maintained on their randomized long-acting injectable risperidone regimen for the duration of the trial.

32 patients were included in the intent-to-treat analysis. No statistically significant differences were found for Attention Vigilance, Declarative Memory, Processing Speed, Reasoning/Problem Solving, Working Memory domains and the Neurocognitive Composite Score. Group specific analysis showed a statistically significant group interaction (p=0.043) with the Social Cognition domain showing in the galantamine group significantly lower scores at endpoint than placebo patients. The PANSS general psychopathology subscale showed significantly higher scores in the galantamine group at endpoint (p=0.05). ANCOVA model for within treatment group comparisons showed a significant increase of 7.3 points for the total PANSS score for the galantamine group.

Galantamine showed no ameliorative effects on cognitive measures in this 6month, double-blind study of patients with schizophrenia treated with an assured and stable antipsychotic medication delivery system. Galantamine may not be an appropriate augmentation agent for cognitive impairments in patients with schizophrenia at the dose used.