By Marilynn Larkin
NEW YORK —Adjunctive intravenous sodium nitroprusside (IV SNP) is not effective for individuals with schizophrenia who have a history of treatment resistance, results of a proof-of-concept clinical trial reveal.
"We were encouraged by the initial studies of IV SNP and optimistic it could be an effective adjunctive treatment for individuals with schizophrenia," Dr. Hannah Brown of Boston Medical Center told Reuters Health by email. "We followed up the initial studies with a well-powered multi-center randomized clinical trial. However, we are disappointed that our results did not demonstrate any type of symptom improvement."
Dr. Brown and colleagues randomly assigned 52 patients to three different two-week treatment sequences: SNP and SNP, placebo and SNP, or placebo and placebo. The mean age across the groups was about 45, and 23% were women. All had failed to achieve a clinically significant response after treatment for at least eight weeks in the previous year with at least one antipsychotic medication at a therapeutic dose.
SNP was given as a single four-hour infusion at 0.5 mcg/kg/min.
The main outcome was the effectiveness of SNP compared with placebo in improving Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores across each two-week phase.
As reported online March 27 in JAMA Psychiatry, there were no significant differences between the SNP and placebo groups at baseline or in changes from baseline for total, positive or negative PANSS-scores, nor were any significant differences in safety or tolerability identified
"Based on our data, we can't recommend the use of SNP for treatment in schizophrenia, although we can't exclude the possibility that studies in certain patient subgroups might find benefit," Dr. Brown said. "We emphasize that this is just one of a number of therapeutic strategies being investigated in schizophrenia, so there's still cause to be optimistic that we will find better treatments."
Dr. Shitij Kapur of the University of Melbourne, coauthor of a related editorial, told Reuters Health, "I was disappointed to see the study results, because as a psychiatrist, I would have much rather the original study was replicated and we had a dramatic new treatment to offer our patients."
"However," he said by email, "the high rate of 'failure to replicate' raises an important question as to why this happens. There are two reasons - one, the original study got it wrong. Second, the replication study missed the finding."
"Data from evaluating hundreds of such studies shows that if the original study was based on a small number of patients - even though the results may be statistically significant (e.g., with a p-value of 0.05) - the chance of later replication is low," he noted.
"Essentially, small studies more often lead to red herrings," Dr. Kapur said. "These findings raise important cautions for the field: scientists must be more sober when making predictions about power and sample size; funding agencies should be careful not to fund too many small under-powered studies; and finally, journals may need to be more rigorous - perhaps requiring internal replication before splashing new findings based on small samples, especially when these are related to clinical treatment possibilities."
SOURCE: http://bit.ly/2VhxY4A and http://bit.ly/2VkBQ4L
JAMA Psych 2019.
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