Lurasidone Improves Psychopathology and Cognition in Treatment-Resistant Schizophrenia

Herbert Y. Meltzer*, Daniel B. Share, Karu Jayathilake, Ronald M. Salomon, Myung A. Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Purpose/Background In addition to clozapine, other atypical antipsychotic drugs pharmacologically similar to clozapine, for example, olanzapine, risperidone, and melperone, are also effective in a similar proportion of treatment-resistant schizophrenia (TRS) patients, 40%. The major goal of this study was to compare 2 doses of lurasidone, another atypical antipsychotic drug, and time to improvement in psychopathology and cognition during a 6-month trial in TRS patients. Methods/Procedures The diagnosis of TRS was based on clinical history and lack of improvement in psychopathology during a 6-week open trial of lurasidone 80 mg/d (phase 1). This was followed by a randomized, double-blind, 24-week trial of lurasidone, comparing 80-and 240-mg/d doses (phase 2). Findings/Results Significant non-dose-related improvement in the Positive and Negative Syndrome Scale-Total and subscales and in 2 of 7 cognitive domains, speed of processing and executive function, were noted. Twenty-eight (41.8%) of 67 patients in the combined sample improved =20% in the Positive and Negative Syndrome Scale-Total. Of the 28 responders, 19 (67.9%) first reached =20% improvement between weeks 6 and 24 during phase 2, including some who had previously failed to respond to clozapine. Implications/Conclusions Improvement with lurasidone is comparable with those previously reported for clozapine, melperone, olanzapine, and risperidone in TRS patients. In addition, this study demonstrated that 80 mg/d lurasidone, an effective and tolerable dose for non-TRS patients, was also effective in TRS patients but required longer duration of treatment. Direct comparison of lurasidone with clozapine in TRS patients is indicated.

Original languageEnglish (US)
Pages (from-to)240-249
Number of pages10
JournalJournal of clinical psychopharmacology
Issue number3
StatePublished - May 1 2020


  • atypical antipsychotic
  • cognition
  • lurasidone
  • treatment-resistant schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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