A preliminary report suggests that sodium nitroprusside can relieve psychosis by regulating the activity of N-methyl-D-aspartate (NMDA) glutamate receptors.
Serdar Dursun, M.D., Ph.D., of the University of Alberta in Edmonton, and colleagues studied 20 patients between the ages of 19 and 40, in an acute phase of schizophrenia diagnosed less than five years ago. The patients were being treated with stable antipsychotics at the time of the infusion. According to research just published in JAMA Psychiatry the investigators administered sodium nitroprusside to 10 patients at 0.5 micrograms per kilogram of body weight per minute for four hours - the lowest recommended dose for humans. They then offered five percent glucose infusion to the other 10 patients over four hours.
The psychiatrists continued to check the patients in both groups for four weeks for schizophrenia symptoms using the 18-item Brief Psychiatric Rating Scale and the negative subscale of the Positive and Negative Syndrome Scale. They also monitored the safety and tolerability sodium nitroprusside, for any psychological or functional effects.
The experts noticed a positive impact of the drug during the infusion within two hours, based on the score with the Brief Rating Scale. The psychiatrists noted similar positive effect on the Positive and Negative Syndrome Scale, as well. The patients continued to show improvements over the four weeks, according to the report. However, none of the patients on glucose infusion manifested any positive findings.
The findings are promising and exciting enough to warrant additional studies with the drug, despite the small size of the study, involving only 20 patients.
"The findings offer further support that NMDA receptors are underperforming in schizophrenia," commented Joseph Coyle, M.D., of Harvard Medical School in a media interview.
"Caution must be exercised until sufficiently powered clinical trials of nitroprusside are performed in patients with schizophrenia," said Coyle.
Indeed, there is a need for studies that look into patients with long-term illness in terms of effect of nitroprusside.
Experts also note that that the study incorporated changes to supplemental medications including benzodiazepines and analgesics 48 hours after the infusion and to antipsychotics after seven days. It is therefore, important to understand how much of the effect seen was due to sodium nitroprusside alone at any point in time.
Nonetheless, "the results clearly show a therapeutic effect of sodium nitroprusside. If this drug is approved for routine clinical use in patients with schizophrenia, this discovery will be an important advance in the pharmacologic treatment of this devastating disorder," the investigators conclude.
