Article

Rapid Improvement of Acute Schizophrenia Symptoms After Intravenous Sodium Nitroprusside A Randomized, Double-blind, Placebo-Controlled Trial

JAMA Psychiatry (Impact Factor: 12.01). 05/2013; 70(7):1-9. DOI: 10.1001/jamapsychiatry.2013.1292
Source: PubMed

ABSTRACT IMPORTANCE The treatment of schizophrenia remains a challenge, and the currently available antipsychotic drugs are slow acting and produce a number of adverse effects. OBJECTIVE To examine the effectiveness and safety of a single intravenous administration of sodium nitroprusside (0.5 μg/kg/min for 4 hours) on the positive, negative, anxiety, and depressive symptoms in patients with schizophrenia. DESIGN Single-center, randomized, double-blind, placebo-controlled trial performed from March 9, 2007, to March 12, 2009. SETTING University teaching hospital in São Paulo, Brazil. PARTICIPANTS Twenty inpatients aged 19 to 40 years with a diagnosis of schizophrenia who were in the first 5 years of the disease who are taking antipsychotics. INTERVENTION Sodium nitroprusside administration. MAIN OUTCOME MEASURES The 18-item Brief Psychiatric Rating Scale and the negative subscale of the Positive and Negative Syndrome Scale. RESULTS After the infusion of sodium nitroprusside, a rapid (within 4 hours) improvement of symptoms was observed. The placebo and experimental groups had significant differences in the 18-item Brief Psychiatric Rating Scale total score and subscale scores, which persisted for 4 weeks after infusion. CONCLUSIONS 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. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01548612.

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Available from: Paulo Belmonte-de-Abreu, Aug 22, 2015
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    • "The precise antipsychotic mechanism of action of SNP is still unclear. Perhaps its antipsychotic effects could start faster than the usual antipsychotic medications because of SNP's capacity to modulate the NMDA–NO–cGMP pathway (Hallak et al., 2013). If the effects of SNP on dopamine are confirmed by future and better designed studies, this may represent an exciting link between glutamate and dopamine, the two transmitters most widely investigated in schizophrenia (Coyle, 2012; Seeman, 2013), and yield important clues for the development of more effective antipsychotic drugs. "
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    • "Its mechanism of action is unknown, but it may be through an anti-inflammatory effect, or an effect on NMDA receptors. Recent work suggests that intravenous sodium nitroprusside may improve negative symptoms (Hallak et al., 2013). This drug is thought to act by generating nitric oxide, which may modulate NMDA receptors. "
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    • "Sodium benzoate , which may increase D-serine by inhibiting D-amino acid oxidase, may also afford similar benefits (Lane et al., 2013). A recent study also found a rapid, robust, and sustained effect of a single administration of sodium nitroprusside in schizophrenic patients, aiming at increasing nitric oxide (Hallak et al., 2013). Intriguingly, this effect does not seem to involve the soluble guanylate cyclase/cGMP pathway (Issy, Pedrazzi, Yoneyama, & Del-Bel, 2014). "
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