A placebo-controlled study of sildenafil effects on cognition in schizophrenia
Abstract
BACKGROUND: Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-D-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. The PDE5 inhibitor sildenafil has been shown to enhance memory in animal models. In addition, neuronal nitric oxide synthase, another component of the NMDA/nitric oxide/cGMP intracellular pathway, has been reported to be dysregulated in schizophrenia patients.
MATERIALS AND METHODS: Seventeen adult schizophrenia outpatients treated with a stable dose of antipsychotic received a single oral dose of placebo, sildenafil 50 mg, and sildenafil 100 mg in random order with a 48-h interval between administrations. Psychiatric symptom ratings and a cognitive battery were performed at baseline and 1 hour following each administration of the study drug. In addition, memory consolidation was examined by testing recall 48 h later, prior to the next administration of the study drug.
RESULTS: Fifteen subjects completed all three treatment conditions. One subject developed irritability and required hospitalization 2 days after receiving sildenafil 100 mg. Neither dose of sildenafil significantly affected cognitive performance or symptom ratings compared to the placebo.
CONCLUSION: Despite evidence for cognitive-enhancing effects of sildenafil in animal models, the strategy for treating putative NMDA receptor-mediated memory…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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