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 Identifier: NCT01548612.

Download full-text


Available from: Paulo Belmonte-de-Abreu, Aug 22, 2015
  • Source
    • "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. "
    Schizophrenia Research 11/2014; 159(2-3). DOI:10.1016/j.schres.2014.08.020 · 4.43 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, there has been increasing emphasis on the importance of motivational symptoms in depression, schizophrenia and other disorders. The present review discusses the conceptual background related to the construct of motivation, and provides a framework that for research on both physiological and pathological aspects of motivation. Particular emphasis is placed on what is known about the neurobiological basis of activational aspects of motivation, including studies from animal models. The role of limbic/prefrontal/striatal circuitry in behavioral activation and effort-related functions is examined, and the utility of behavioral tasks of effort-based decision making as models of motivational symptoms is discussed. We also review the neurobiology of motivational symptoms in relation to psychopathology, and issues related to the language used to characterize motivational dysfunctions are considered. The literature suggests that research on the neurobiology of motivational dysfunction in psychopathology, at both the clinical and preclinical levels, could inform the development of novel and more effective treatments for a range of CNS disorders.
    European Neuropsychopharmacology 09/2014; DOI:10.1016/j.euroneuro.2014.08.014 · 5.40 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The management of schizophrenia endophenotypes, namely positive, negative, and cognitive symptoms is still an open goal, justifying the search of novel therapeutic avenues. We now review the evidence supporting the interest in targeting the adenosine modulation system to counteract the core features of schizophrenia. This interest is forwarded by the combined ability of strategies aimed at bolstering adenosine levels together with the increasingly recognized impact of adenosine A2A receptors to control dopaminergic signaling, working memory, and behavioral sensitization; this is further heralded by the suggested clinical effectiveness of therapies increasing extracellular adenosine such as dipyridamole and allopurinol and the emergent recognition of a role for adenosine in neurodevelopment. Finally, the combined role of A1 and A2A receptors in assisting the implementation of adaptive changes and encoding of information salience in neuronal circuits together with the adaptive alterations of A1 and A2A receptor density upon brain dysfunction prompts the novel working hypothesis that the parallel imbalance of adenosine formation and of A1 and A2A receptors blurs the adequate encoding of information salience in neuronal circuits, which we propose to be a core pathogenic feature in the development of schizophrenia endophenotypes. This proposal should also provide a rationale to assist the design of future therapeutic intervention targeting the adenosine modulation system to manage schizophrenia endophenotypes: these should not be based only on an attempt to target adenosine kinase-A1 receptors or only A2A receptors, but should instead simultaneously target these two arms of the adenosine modulation system.
    International Review of Neurobiology 01/2014; 119C:395-449. DOI:10.1016/B978-0-12-801022-8.00016-7 · 2.46 Impact Factor
Show more