Steven Dubovsky, MD reviewing Bugarski-Kirola D et al. Biol Psychiatry 2016 Dec 15.

Although the investigatory drug doesn't work, the study highlights the importance of clinician–patient interactions in improving negative symptoms.

Deficits in the NMDA receptor (NMDAR) signaling have been associated with negative symptoms of schizophrenia, and preliminary data suggest that drugs that enhance activity of glycine (a co-agonist linked to the NMDAR) can improve negative symptoms (NEJM JW Psychiatry Jun 2014 and JAMA Psychiatry 2014; 71:637). In view of this evidence, the manufacturer of the investigatory drug bitopertin, an inhibitor of glycine transporter type 1 (i.e., a glycine reuptake inhibitor), conducted three 24-week, multicenter, randomized, placebo-controlled trials of various bitopertin doses in patients with stable schizophrenia and persistent negative symptoms.

All patients were treated with antipsychotic drugs (excluding clozapine). After an interim analysis demonstrated probable lack of benefit, the first study, involving doses of 10 and 20 mg, was discontinued. The other two trials involved 605 patients (5- and 10-mg doses) and 594 patients (10- and 20-mg doses). Although the study drug was well tolerated, there was no evidence of superiority of any dose to placebo (on the primary outcome, a negative-symptoms scale, response rates in all groups approximated 60%).

CITATION(S):

Bugarski-Kirola D et al. Bitopertin in negative symptoms of schizophrenia — results from the phase III FlashLyte and DayLyte studies. Biol Psychiatry 2016 Dec 15; [e-pub]. 

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