Guanfacine and cognitive remediation with social skills training appear to be effective, well-tolerated treatment modes for schizotypal personality disorder, according to study data published in The American Journal of Psychiatry.

Investigators conducted a double-blind randomized controlled trial to assess the effects of guanfacine augmentation on cognitive remediation and social skills training. A total of 28 participants with schizotypal personality disorder were randomly assigned to 8 weeks of cognitive remediation and social skills training, augmented either with guanfacine (n=15) or placebo (n=13). Cognitive remediation therapy was administered using a multimedia Windows-based program and consisted of attentional functioning and problem-solving exercises. Twice-weekly social skills training was delivered by a doctoral-level clinical psychologist in a group therapy environment. Participants assigned to guanfacine were titrated to 2.0 mg/day during the first 2 weeks and remained on 2.0 mg/day for the duration of the study. Cognition, social cognition, and functional capacity were assessed over the study course using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), Movie for the Assessment of Social Cognition, and the University of California San Diego Performance-Based Skills Assessment.

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In the guanfacine group, 11 (73%) participants were men and the mean (standard deviation) age was 46.5 (12.2) years; in the placebo group, 10 (77%) participants were men and the mean (standard deviation) age was 40.7 (10.1) years. Substantial improvements were observed from baseline to posttreatment for all patients in the MCCB speed of processing (P =.015), verbal learning (P =.011), and visual learning (P =.032) domains. A significant time-by-medication interaction was also observed for the MCCB reasoning and problem-solving domain (P =.005) and for University of California San Diego Performance-Based Skills Assessment total score (P =.026). Patients receiving guanfacine demonstrated greater improvements over time compared with patients receiving placebo. The time-by-medication interaction for Movie for the Assessment of Social Cognition hypomentalization errors approached statistical significance (P =.07). However, no statistically significant change was observed in MCCB working memory or supplemental neuropsychological assessments (P >.05).

These data suggest that patients with schizotypal personality disorder may benefit from cognitive remediation therapy with social skills training. In addition, guanfacine may augment the benefits of these combined therapies, although further research with a larger study cohort is necessary to confirm these findings.


McClure MM, Graff F, Triebwasser J, et al. Guanfacine augmentation of a combined intervention of computerized cognitive remediation therapy and social skills training for schizotypal personality disorder [published online January 18, 2019]. Am J Psychiatry. doi: 10.1176/appi.ajp.2018.18030349