Nancy A. Melville

June 08, 2017

MIAMI – A risk score based on genetic factors associated with risk for schizophrenia can be an effective predictor of response to antipsychotic medication following a first episode of psychosis (FEP), new research shows.

"Patients with higher polygenic risk scores tended to have less improvement with antipsychotic drug treatment," said first author Jianping Zhang, MD, of Zucker Hillside Hospital, New York City, in presenting the findings here at the American Society of Clinical Psychopharmacology (ASCP) 2017 Annual Meeting.

"Clinicians should individualize treatment decisions, weighing different aspects of efficacy, tolerability, availability, and cost."

The landmark Psychiatric Genomics Consortium (PGC) genome-wide association study (GWAS), which was published in Nature in 2014, identified 108 independently associated loci across the genome as being linked to an increased risk for schizophrenia.

In investigating whether the genes could predict treatment response, Dr Zhang and colleagues used software that produced polygenic risk scores on the basis of PGC GWAS study results. They applied the scores to four clinical trial cohorts with data on patients that included their genomic profiles and FEP experiences.

The four trials included the European First Episode Schizophrenia Trial (EUFEST), with 141 FEP patients; the Zucker Hillside Hospital First Episode Schizophrenia Clinical Trial (ZHH-FE), which included 77 FEP patients; the Spanish First Episode Psychosis (SFEP) study, involving 192 FEP patients; and a clinical trial conducted as part of the Center for Intervention Development and Applied Research at ZHH (CIDAR), with 100 FEP patients.

In combining the data from the four cohorts to establish polygenic risk scores, the authors found that a higher risk score was significantly predictive of symptom scores at a 3-month follow-up (P = .003), considered to be indicative of a lower response to antipsychotic treatment.

The association between the polygenic risk score and treatment response was significant in the ZHH-FE trial, which assessed symptoms according to the Brief Psychiatric Rating Scale (BPRS; P = .013); the EUFEST trial, which assessed symptoms according to the total score on the Positive and Negative Symptoms Scale (P = .012); and the SFEP (P = .006). Risk score did not significantly predict 3-month symptom scores in the CIDAR cohort, which also used the BPRS (P > .50).

"These findings suggest that polygenic schizophrenia risk scores may also be related to antipsychotic drug response. Further analysis is needed to elucidate a more defined genomic profile for antipsychotic drug response," said Dr Zhang.

Critical Value

A second study presented in the session further underscored the potential critical value of predicting which patients may, and which may not, respond to antipsychotic medications.

The meta-analysis included 2354 abstracts and 91 studies of schizophrenia and suicidality. It showed that poor treatment compliance was among the leading factors associated with completed suicide; patients were more than three times more likely to complete a suicide if they were noncompliant with medication (odds ratio [OR], 3.17; P < .0001).

Other leading risk factors for completed suicide included current delusions (OR, 7.83; P = .0005), hopelessness (OR, 5.28; P = .004), being white (OR, 4.92; P = .04), and having a history of attempted suicide (OR, 3.54; P < .0001).

"In terms of noncompliance, our study was not able to determine the types of antipsychotics that were most associated with the increased risk of suicide," first author Fang Yang, MD, PhD, of the University of Texas Health Science Center at Houston, told Medscape Medical News.

"Most studies are very general and don't specify first-generation or second-generation antipsychotics, but that should be a question for future studies."

The authors of both studies have disclosed no relevant financial relationships.

American Society of Clinical Psychopharmacology (ASCP) 2017 Annual Meeting. Abstracts 3000977 and 3000919, presented May 31, 2017.

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