Treatment-resistant schizophrenia - A RCT on the effectiveness of repeated-dose sodium nitroprusside

Sodium nitroprusside (SNP) has shown efficacy in schizophrenia in early stages of the disease in a previous study, but in more recent studies it has not shown efficacy in patients with longer disease duration. In present study, we evaluated the efficacy of repeated-dose SNP in treatment-resistant schizophrenia.

This was a double-blind, randomized, placebo-controlled trial. Twenty DSM-IV schizophrenia subjects, aged 18-60 years, with a history of nonresponse to ≥2 trials of antipsychotics of adequate dose and duration (≥6 weeks) were enrolled. Participants received SNP or placebo 4-hour infusions at 0.5 μg/kg/min. A total of 4 infusions and 4 follow-up evaluations, with an interval of 2 weeks, were performed. Severity of symptoms were assessed by using Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS-18) and Clinical Global Impression (CGI) scales.

SNP and placebo groups did not differ at baseline or in change from baseline for PANSS-total (F = 0.525; p = 0.841), PANSS-positive (F = 0.32; p = 0.958), PANSS-negative (F = 1.05; p = 0.483), BPRS (F = 0.615; p = 0.734), or CGI-S (F = 1.11; p = 0.416) scores. SNP was well tolerated and showed a good safety profile.

Although preliminary, the present findings suggest that SNP is not efficacious in TRS, reinforcing previous studies that have not demonstrated symptom improvement in chronic schizophrenia subjects. At this time, it is conceivable to speculate that efficacy of SNP might be restricted to early stages of disease.