Brazil: The Use of Nitrous Prusside for Schizophrenia

nitrous prusside, schizophrenia, mental health

In 2013, Drs. Jaime Hallak, Joao Paulo Maia-de-Oliveira and associates in Ribeirao Preto, Brazil, published results from a randomized controlled trial of intravenous nitroprusside in schizophrenia. Two Canadian researchers from the University of Alberta collaborated on the trial. This study was the first to find that sodium nitroprusside, a treatment for hypertensive crises, has a rapid and prolonged effect on both positive and negative symptoms in patients with acute psychosis. The presumed mechanism is enhancement of nitric oxide in the central nervous system, which may modulate the NMDA receptor-cGMP pathway. In normotensive patients, nitroprusside has minimal effect on blood pressure, and cyanide accumulation is a theoretical concern but occurs only after 72 hours or more of continuous infusion. In treating schizophrenia, the infusion dose is 0.5 mg/kg/minute for four hours.

In the initial trial published in JAMA Psychiatry, Hallak’s team used the Brief Psychiatric Rating Scale and the negative subscale of the Positive and Negative Syndrome Scale (PANSS) as outcome measures. A significant effect on certain components occurred within the first two to three hours of treatment, and improvement endured for four weeks. All the patients were also receiving an antipsychotic other than clozapine.

I met with Jaime, Joao Paulo and their team at the University of Sao Paulo Hospital in Ribeirao Preto and was able to observe a treatment. When I first met the patient, whose infusion had begun 10 minutes before, she appeared anxious and tended to avoid eye contact. When I returned 90 minutes later, she was engaged in an art activity and was eager to show me what she had created. She smiled broadly and even tested her English vocabulary a little. The researchers said that they often see an improvement in the patients’ affect over the course of the infusion, and they are trying to find ways to measure this more objectively. Although data are still limited, the effect in treatment-resistant patients tends to be more delayed.

Further studies of nitrous prusside in Ribeiroa Preto are underway, including for treatment-resistant patients, some on clozapine, and on neurophysiologic effects as detected with fMRI and event-related potential. Because the benefits of the treatment begin to wane after four weeks, they are planning a controlled trial of weekly nitrous prusside infusions for four weeks followed by 60 days of observation.
Reference
Hallak JEC, Maia-de-Oliveira JP, Abroa J, et al. Rapid Improvement of Acute Schizophrenia Symptoms After Intravenous Sodium Nitroprusside: A Randomized, Double-blind, Placebo-Controlled Trial. JAMA Psychiatry. 2013;70:668-676. Abstract
Photo: Left to right: Dr. Jaime Hallak, Dr. Joao Paolo Maia-de-Oliveira, Juliana Almeida (audiologist), their patient and her mother

7 thoughts on “Brazil: The Use of Nitrous Prusside for Schizophrenia

  1. Dear dr White,

    is there any explanation why this research is going on so slow? Or we, as affected people are just impatient… But it seems, it started a long time ago (by the information from clinicalresearch site) and although it seems extremely promissing, no news have been published since the last year. To me, it looks like it could go a little faster , be a little broader etc. Do they lack funds to continue quicker? Do they face any problems of such kind? Or at least, when do they expect to publish some new results?

    Many thanks in advance,
    Dejana

    • A multi-site trial is getting underway in the United States which you can learn more about here http://clinicaltrials.gov/show/NCT02164981

      In Canada, it will require special permission from Health Canada to use nitrous prusside in Canada to treat schizophrenia. Things can happen more quickly in Brazil which is why the first trial took place there.

  2. BC’s “Fair”Pharmacare ignores the plethora of complimentary research available from other fields and, instead, continues to force brain and body disabling drugs on women who probably just need their hormones balanced, NOT eradicated by neuroleptics. Is it any wonder that anti-psychotic medications sensitize people to further psychotic episodes by decimating their hormonal cascade, among other methods of biochemical destruction?

    “…the brain depends solely on blood flow to function. In fact, roughly one-third of the brain is composed of blood vessels.[5] Estrogen increases cerebral perfusion…[3,6,7] By binding to receptors in the endothelium, ESTROGEN stimulates the release of NITRIC OXIDE, which causes vasodilation.”

    Shepherd, J.E., “Effects of estrogen on cognition, mood, and degenerative brain diseases.” J Am Pharm Assoc. 2001;41(2)

  3. I am not an expert in hormonal treatments, but estrogen has its own adverse effects which were shown in the Women’s Health study. Breast cancer is a very feared disease, so benefits have to outweigh risks. The same is true of antipsychotics, but we have few alternatives. I hope governments and pharmaceutical companies will invest more in finding new treatments for schizophrenia, but investment in this field has lagged.

  4. This sounds very promising! My loved one is doing “ok” on olanzopine but he hates the weight gain! It would be wonderful to have something that would let reduce the dosage. Please continue to keep us informed Dr White!
    Marilyn

  5. Has any more progress been made since this article was published? It sounds so promising. I wonder if Health Canada would let people try it, in a trial, here in Canada?

    • So far no clinical trial has been undertaken in Canada, although some researchers hope to organize one if they can obtain the necessary funding.

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