Guanfacine Augmentation of a Combined Intervention of Computerized Cognitive Remediation Therapy and Social Skills Training for Schizotypal Personality Disorder

Abstract

Objective. Impaired cognition is a hallmark of schizophrenia and spectrum disorders such as schizotypal personality disorder, and is the best predictor of functional outcome. Cognitive remediation therapy has demonstrated efficacy for improving cognition and augmenting other rehabilitation efforts in schizophrenia, with gains in real-world functioning. Pharmacological augmentation of cognitive remediation has been attempted but the effects of augmentation on combined therapies such as cognitive remediation and social skills training has not been studied. Method. Twenty-eight participants with schizotypal personality disorder enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of guanfacine plus cognitive remediation + social skills training (15 guanfacine, 13 placebo). Cognition was assessed with the MATRICS Clinical Consensus Battery (MCCB), social cognition with the Movie for the Assessment of Social Cognition (MASC), and functional capacity with the UCSD Performance Based Skills Assessment (UPSA). Results. There was a statistically significant time (pre- versus post-treatment) effect for MCCB speed of processing, verbal learning, and visual learning, and UPSA total score. There was a significant time x medication condition (guanfacine, placebo) interaction for MCCB reasoning and problem solving, and UPSA total score; the time x treatment condition interaction approached significance for MASC hypomentalizing errors. Conclusions. In this trial, both the agent guanfacine and our psychosocial intervention of cognitive remediation plus social skills training were well-tolerated, with no side effects or drop-outs. Participants treated with cognitive remediation plus social skills training plus guanfacine demonstrated statistically significant improvements in reasoning and problem solving, as well as in functional capacity and possibly social cognition, compared to those treated with cognitive remediation plus social skills training plus placebo. Cognitive remediation plus social skills training may be an appropriate intervention for individuals with schizotypal personality disorder and guanfacine appears to be a promising agent to augment cognitive remediation plus social skills training in this population.

Severe childhood trauma and clinical and neurocognitive features in schizotypal personality disorder

“…Data on neurocognitive measures were only available for a subset of SPD ( N = 32) and HC ( N = 23) individuals, who participated in study protocols that involved cognitive testing. For a full description of recruitment and inclusion/exclusion criteria for this subset of individuals, see previous publications .…”

Functional deficits in attenuated psychosis syndrome and related conditions: Current and future treatment options

“…CCT has also demonstrated efficacy in APS, SPD, and FEP, suggesting potential for this route of therapy (Fisher et al, 2014; Hooker et al, 2014; Loewy et al, 2016b). Recently, the use of combined therapy (CCT plus pharmacological intervention i.e., guanfacine) has demonstrated some incremental benefit in the treatment of SPD (McClure et al, 2019).…”

“…Outcomes were examined using the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) and UPSA. Combined therapy led to significant improvements in reasoning and problem-solving, and UPSA total score, compared with CCT plus placebo (McClure et al, 2019). Additionally, CCT was associated, across guanfacine treatment status, with improvements in speed of processing, verbal learning, and visual learning (McClure et al, 2019).…”

“…Combined therapy led to significant improvements in reasoning and problem-solving, and UPSA total score, compared with CCT plus placebo (McClure et al, 2019). Additionally, CCT was associated, across guanfacine treatment status, with improvements in speed of processing, verbal learning, and visual learning (McClure et al, 2019). The effect sizes for these improvements were considerably larger than the expected effect sizes seen with retesting and practice alone on the MCCB (Keefe et al, 2017).…”

Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species

“…Recent studies indicate that symptoms of schizotypy have a linear relationship to severe childhood trauma, and are associated with worse PFC cognitive functioning ( Velikonja et al, 2019 ). The work of Margaret McClure has shown that guanfacine can improve working memory ( McClure, Barch, Romero, Harvey, & Siever, 2007 ) and significantly enhance the beneficial effects of cognitive remediation ( McClure et al, 2019 ) in schizotypal patients. The latter is particularly interesting, as a combined approach of boosting PFC physiology while engaged in cognitive training may optimize success.…”