Skip to main content Accessibility help
×
Home

Contents:

Information:

  • Access
  • Cited by 3

Actions:

      • Send article to Kindle

        To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Letter to the Editor: Sodium nitroprusside for schizophrenia: could methodological variables account for the different results obtained?
        Available formats
        ×

        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Letter to the Editor: Sodium nitroprusside for schizophrenia: could methodological variables account for the different results obtained?
        Available formats
        ×

        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Letter to the Editor: Sodium nitroprusside for schizophrenia: could methodological variables account for the different results obtained?
        Available formats
        ×
Export citation

We read with interest the paper by Stone et al. (2016) about the effect of sodium nitroprusside (SNP) in patients with schizophrenia. It was a controlled trial where 20 subjects on antipsychotics received an infusion of SNP (0.5 µg/kg per min for 4 h) or placebo. The participants were assessed at baseline, immediately after the infusion, and 4 weeks later. No differences in outcomes were found between SNP and placebo (Stone et al. 2016).

Previously, we reported that SNP displays antipsychotic activity in animal models of schizophrenia (Bujas-Bobanovic et al. 2000; Maia-de-Oliveira et al. 2015a ) and in schizophrenia patients taking antipsychotics (Hallak et al. 2013; Maia-de-Oliveira et al. 2014). We found that SNP improved some cognitive deficits in schizophrenia patients (Maia-de-Oliveira et al. 2015 b) and long-term ketamine-induced memory deficits in rats (Kandratavicius et al. 2015). Trevlopoulou et al. (2016) reported that SNP attenuated ketamine-induced short-term recognition memory deficits and social isolation in rats.

Stone et al. (2016) were not able to replicate our main findings. The authors argued that beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms. Hallak et al. (2013) used the Bech's version of the Brief Psychiatric Rating Scale that rates from 0 to 4 (Bech et al. 1986), while Stone et al. (2016) used the Overall & Goram (1962) version, which rates from 1 to 7, suggesting that in the Stone et al. (2016) study participants were less symptomatic. Indeed, Hallak et al. (2013) worked with subjects with less than 5 years of disease and who were so severely ill they were hospitalized; symptoms were also recorded at baseline and at multiple times between infusion and 4 weeks.

Stone et al. (2016) also seem to have worked with a population presenting other features that could potentially affect their final findings such as the presence of two schizo-affective disorder patients and seven subjects currently using cannabis; it was not clear if there was other illicit substance use. Furthermore, the majority of patients were current smokers (n = 12). Since it is well known that cigarette smoking induces a reduction in NO (Guo et al. 2006; Csordas & Bernhard, 2013), this characteristic may have influenced the SNP efficacy. Moreover, the majority of patients were black (n = 15, denoted as ‘black British and black other’). Since black Americans and black South Africans have been reported to present with attenuated SNP vascular effects (Stein et al. 1997; Pienaar et al. 2014), perhaps the same happens concerning SNP's antipsychotic and cognitive effects; it may be inappropriate to compare these groups from three different countries, but it does raise the question of possible ethnic differences in responses to SNP.

In contrast to the Hallak et al. (2013) study, Stone et al. (2016) found significant reduction of blood pressure and increase in heart rate during the SNP treatment. Could these cardiac alterations have negatively influenced the performance of the SNP group?

We believe that several variables could account for the different results reported, which points out the importance of avoiding possible confounding factors in future studies on this drug.

Declaration of Interest

All of the authors of this letter were also authors on the Hallak et al. (2013) paper.

References

Bech, P, Kastrup, M, Rafaelsen, OJ (1986). Mini-compendium of rating scales for states of anxiety, depression, mania schizophrenia, with corresponding DSM-III syndromes. Acta Psychiatrica Scandinavica Supplementum 326, 137.
Bujas-Bobanovic, M, Bird, DC, Robertson, HA, Dursun, SM (2000). Blockade of phencyclidine-induced effects by a nitric oxide donor. British Journal of Pharmacology 130, 10051012.
Csordas, A, Bernhard, D (2013). The biology behind the atherothrombotic effects of cigarette smoke. Nature Reviews Cardiology 10, 219230.
Guo, X, Oldham, MJ, Kleinman, MT, Phalen, RF, Kassab, GS (2006). Effect of cigarette smoking on nitric oxide, structural, and mechanical properties of mouse arteries. American Journal of Physiology – Heart and Circulatory Physiology 291, 23542361.
Hallak, JE, Maia-de-Oliveira, JP, Abrao, J, Evora, PR, Zuardi, AW, Crippa, JA, Belmonte-de-Abreu, P, Baker, GB, Dursun, SM (2013). Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: a randomized, double-blind, placebo-controlled trial. JAMA Psychiatry 70, 668676.
Kandratavicius, L, Balista, PA, Wolf, DC, Abrao, J, Evora, PR, Rodrigues, AJ, Chaves, C, Maia-de-Oliveira, JP, Leite, JP, Dursun, SM, Baker, GB, Guimaraes, FS, Hallak, JE (2015). Effects of nitric oxide-related compounds in the acute ketamine animal model of schizophrenia. BMC Neuroscience 16, 9.
Maia-de-Oliveira, JP, Abrao, J, Evora, PR, Zuardi, AW, Crippa, JA, Belmonte-de-Abreu, P, Baker, GB, Dursun, SM, Hallak, JE (2015 b). The effects of sodium nitroprusside treatment on cognitive deficits in schizophrenia: a pilot study. Journal of Clinical Psychopharmacology 35, 8385.
Maia-de-Oliveira, JP, Belmonte-de-Abreu, P, Bressan, RA, Cachoeira, C, Baker, GB, Dursun, SM, Hallak, JE (2014). Sodium nitroprusside treatment of clozapine-refractory schizophrenia. Journal of Clinical Psychopharmacology 34, 761763.
Maia-de-Oliveira, JP, Lobão-Soares, B, Ramalho, T, Gavioli, EC, Soares, VP, Teixeira, L, Baker, GB, Dursun, SM, Hallak, JE (2015 a). Nitroprusside single-dose prevents the psychosis-like behavior induced by ketamine in rats for up to one week. Schizophrenia Research 162, 211215.
Overall, JE, Goram, DR (1962). The brief psychiatric rating scale. Psychological Reports 10, 799812.
Pienaar, PR, Micklesfield, LK, Gill, JM, Shore, AC, Gooding, KM, Levitt, NS, Lambert, EV (2014). Ethnic differences in microvascular function in apparently healthy South African men and women. Experimental Physiology 99, 985994.
Stein, CM, Lang, CC, Nelson, R, Brown, M, Wood, AJ (1997). Vasodilation in black Americans: attenuated nitric oxide-mediated responses. Clinical Pharmacology and Therapeutics 62, 436443.
Stone, JM, Morrison, PD, Koychev, I, Gao, F, Reilly, TJ, Kolanko, M, Mohammadinasab, A, Kapur, S, McGuire, PK (2016). The effect of sodium nitroprusside on psychotic symptoms and spatial working memory in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. Psychological Medicine. Published online 22 September 2016. doi:10.1017/S0033291716002245.
Trevlopoulou, A, Touzlatzi, N, Pitsikas, N (2016). The nitric oxide donor sodium nitroprusside attenuates recognition memory deficits and social withdrawal produced by the NMDA receptor antagonist ketamine and induces anxiolytic-like behaviour in rats. Psychopharmacology (Berlin) 233, 10451054.