Benzoate and not benzodiazepines for antipsychotic augmentation

Dr. Jari Tiihonen, Professor of Clinical Neuroscience at the Karolinska Institure in Stockholm, Sweden, discussed findings from his research on polypharmacy in people with schizophrenia on September 20 at the 7th Annual Pacific Psychopharmacology Conference. Using national databases in Finland, his team examined prescription medications and all-cause mortality in a cohort of 2,588 patients during 7 years. Antipsychotic polypharmacy was not associated with increased mortality, and antidepressant use was associated with a decreased risk of death by suicide. In contrast, benzodiazepine use was associated with an increase in suicide and all-cause mortality. Dr. Tiihonen speculated that the sedative effects of benzodiazepines may predispose to unintentional injuries, and withdrawal symptoms may increase agitation and dysphoria which could elevate the risk of suicide.

As for new findings in treatment-resistant schizophrenia, Dr. Tiihonen mentioned the recently published clinical trial of famotidine (see my blog post of July 14). His group is now attempting a replication for which they plan to recruit 140 patients. He also called attention to a randomized clinical trial of sodium benzoate at a dose of 1 gram daily which was presented at the December, 2012 meeting of the American College of Neuropsychopharmacology. The researchers added benzoate or placebo to treatment of 52 patients with chronic schizophrenia “stabilized with antipsychotics for 3 months or longer.” According to the abstract posted on the ACNP Web site, at 6 weeks of treatment, the benzoate group showed significant improvement in PANSS total, positive, and negative scales, as well as in overall neurocognition. The effect size on PANSS total was 1.76, which is very large. It’s not clear if these patients met the usual definition of treatment resistance, i.e. poor response to adequate trials of two antipsychotics, but we should know more soon as the study is in press.

Reference

Tsai GE, Lane H-Y, Green MF. A randomized, double-blind, placebo-controlled add-on treatment of benzoate, a D-amino acid oxidase Inhibitor, for schizophrenia. Neuropsychopharmacology. 2012; 38: S198-S313. Available at: http://www.nature.com/npp/journal/v38/n1s/full/npp2012220a.html (poster T162)

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