Hypertension drug shows schizophrenia promise
medwireNews: Results from a proof-of-concept study point to a role for sodium nitroprusside in the treatment of schizophrenia.
A single intravenous dose of the drug, which is approved for the treatment of severe hypertension, led to a rapid and long-lasting improvement in positive, negative, anxiety, and depressive symptoms of patients, report Serdar Dursun (University of Alberta, Edmonton, Canada) and co-workers.
The study, which appears in JAMA Psychiatry, included 20 patients, aged 19-40 years, diagnosed with schizophrenia within the past 5 years and admitted to hospital during an acute psychotic episode. The patients were randomly assigned to receive sodium nitroprusside (0.5 µg/kg per min over 4 h, n=10) or placebo in addition to antipsychotic medications.
Within 4 hours of sodium nitroprusside infusion, most of the patients recorded a significant improvement in their total 18-item Brief Psychiatric Rating Scale score compared with controls.
Sodium nitroprusside was also associated with significant benefits on the Brief Psychiatric Rating Scale subscales for thinking disorders and anxiety-depression compared with placebo, as well as significant improvements on Positive and Negative Syndrome Scale-negative subscale scores.
"Approval of sodium nitroprusside infusions for the treatment of schizophrenia could significantly improve patient care in emergency and acute care settings, and the future development of alternative formulations more conducive to long-term use could be effective for maintenance therapy," the team suggests.
In an accompanying editorial, Joseph Coyle (Harvard Medical School, Boston, Massachusetts, USA) emphasizes that "caution must be exercised until sufficiently powered clinical trials of nitroprusside are performed in patients with schizophrenia."
Nevertheless, he notes that the study follows "an increasingly compelling body of evidence" that hypofunction of the N-methyl-D-aspartate (NMDA) receptor may play a key role in the development of schizophrenia, especially negative symptoms and cognitive impairment.
"Nitroprusside, after infusion, is converted to nitric oxide, thereby bypassing brain NMDA receptors to directly elevate tissue nitric oxide levels," Coyle explains.
NMDA receptor stimulation is known to activate nitric oxide synthase and the production of nitric oxide. This in turn leads to synthesis of cyclic guanosine monophosphate, which is associated with neural plasticity, the commentator says.
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Lynda Williams, Senior medwireNews Reporter