Patients experiencing psychosis quickly improved after a single infusion of sodium nitroprusside, an antihypertensive agent, according to a new study published in JAMA Psychiatry.
Sodium nitroprusside is used to treat severe hypertension. But there is also evidence that it also regulates the activity of N-methyl-D-aspartate (NMDA) glutamate receptors, said the researchers.
Since blocking those receptors in animals leads to psychosis-like behavior, the researchers wondered if the drug could benefit humans with schizophrenia.
In a small randomized trial, many patients experienced a diminishing of their symptoms within four hours, while those who got a matching placebo did not, according to Serdar Dursun, M.D., Ph.D., of the University of Alberta in Edmonton, and colleagues.
The improvements lasted up to four weeks without any noticeable adverse effects.
Although the results should be considered preliminary because of the size of the study — only 20 patients — the authors said that the findings “are exciting in terms of effectiveness of the drug.”
The study involved 20 patients, in an acute phase of schizophrenia, all of whom required inpatient care. The participants were between the ages of 19 and 40 and were in the first five years since diagnosis. All were on stable antipsychotics at the time of the infusion.
Ten patients received sodium nitroprusside at 0.5 micrograms per kilogram of body weight per minute for four hours – the lowest recommended dose for humans. The remaining 10 patients got 5 percent glucose, also infused for four hours.
During the infusions and for four weeks afterward, psychiatrists monitored schizophrenia symptoms using the 18-item Brief Psychiatric Rating Scale and the negative subscale of the Positive and Negative Syndrome Scale. They also measured safety and tolerability of the drug, both physiologically and psychologically.
During the infusion, they found a positive effect on the brief rating scale that was apparent by the second hour. The effect was seen in all patients getting the drug, but not in any placebo patient.
A similar rapid effect was observed on the positive-negative symptom scale. On both scales, the improvement continued for at least four weeks, the researchers reported.
The findings offer further support that NMDA receptors are underperforming in schizophrenia, commented Joseph Coyle, M.D., of Harvard Medical School.
Coyle noted that the results are consistent with other studies that involve those receptors. But, he said, the current study remains too small to justify changes in clinical practice.
“Caution must be exercised until sufficiently powered clinical trials of nitroprusside are performed in patients with schizophrenia,” said Coyle.
The researchers note that participants were fairly early in their disease course. Future research, they said, should test the drug in patients with long-term illness.
They also noted that the study allowed for changes to supplemental medications (such as benzodiazepines and analgesics) 48 hours after the infusion and to antipsychotics after seven days. Because of this, there is “uncertainty to the antipsychotic effects of sodium nitroprusside alone at later time points.”
Source: JAMA Psychiatry