Is adjunctive intravenous sodium nitroprusside an efficacious and safe treatment for individuals with schizophrenia who have some degree of treatment resistance?
In this multicenter, randomized double-blind clinical trial of 52 adults with chronic schizophrenia treated with antipsychotic medication, no improvement was seen in positive, negative, or cognitive symptoms after a 4-hour sodium nitroprusside infusion at 0.5 μg/kg/min; furthermore, there were no differences in response when stratified by clozapine treatment status. Overall, the treatment was well tolerated.
Results of this well-powered clinical trial suggest that adding intravenous sodium nitroprusside infused at 0.5 μg/kg/min is not an efficacious treatment for individuals with schizophrenia with some history of treatment resistance.
Antipsychotic medications for the treatment of schizophrenia have limitations, and new treatments are needed. A prior pilot investigation suggested that adjunctive sodium nitroprusside (SNP) administered intravenously had rapid efficacy in the treatment of patients with schizophrenia.
To determine the efficacy and tolerability of intravenous SNP infused at a rate of 0.5 μg/kg/min for 4 hours in patients with schizophrenia with some degree of treatment resistance.
Design, Setting, and Participants
Multicenter, randomized, double-blind acute treatment study using a sequential parallel comparison design conducted in two 2-week phases at 4 academic medical centers beginning May 20, 2015, and ending March 31, 2017. Participants were adults 18 to 65 years of age with a diagnosis of schizophrenia as confirmed by the Structured Clinical Interview for DSM-IV, taking antipsychotic medication for at least 8 weeks, and had at least 1 failed trial of an antipsychotic medication within the past year. A total of 90 participants consented, 60 participants enrolled, and 52 participants were included in the analyses. A modified intent-to-treat analysis was used.
Participants were randomized in a 1:1:1 ratio to 1 of 3 treatment sequences: SNP and SNP, placebo and SNP, and placebo and placebo. The SNP and SNP group received SNP in phase 1 and SNP in phase 2 for the purpose of blinding, but the data from phase 2 were not included in the results. The placebo and SNP group received placebo in phase 1 and SNP in phase 2. If there was no response to placebo in phase 1, data from phase 2 were included in the analyses. The placebo and placebo group received placebo in both phases; if there was no response to placebo in phase 1, data from phase 2 were included in the analyses.
Main Outcomes and Measures
Effectiveness of SNP compared with placebo in improving Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores across each 2-week phase.
Fifty-two participants (12 women and 40 men) were included in the study. In the SNP and SNP group, the mean (SD) age was 47.1 (10.5) years. In the placebo and SNP group, the mean (SD) age was 45.9 (12.3) years. In the placebo and placebo group, the mean (SD) age was 40.4 (11.0) years. There were no significant differences between the SNP and placebo groups at baseline or in change from baseline for PANSS-total (weighted β = –1.04; z = –0.59; P = .57), PANSS-positive (weighted β = –0.62; z = –0.93; P = .35), or PANSS-negative (weighted β = –0.12; z = –0.19; P = .85) scores. No significant differences in safety or tolerability measures were identified.
Conclusions and Relevance
Although intravenous SNP is well tolerated, it was not an efficacious adjunctive treatment of positive or negative symptoms of psychosis among outpatients with schizophrenia with prior history of treatment resistance.
ClinicalTrials.gov identifier: NCT02164981
Brown HE, Freudenreich O, Fan X, et al. Efficacy and Tolerability of Adjunctive Intravenous Sodium Nitroprusside Treatment for Outpatients With Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2019;76(7):691–699. doi:https://doi.org/10.1001/jamapsychiatry.2019.0151
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