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Multigene PGx Testing Improves Outcomes for Schizophrenia Patients, Randomized Study Shows

NEW YORK – Patients with schizophrenia experienced better outcomes when their doctors used a multigene panel to inform treatment decisions than those who received the standard care within a study, investigators reported in JAMA Network Open on Friday.

In the study, conducted from March 2020 to March 2022, investigators enrolled 210 Chinese Han men hospitalized with schizophrenia at Peking University Sixth Hospital in Beijing and Second People's Hospital of Guizhou Province in Guiyang and randomized them to receive either pharmacogenomics-guided treatment or standard care without genetic testing for 12 weeks. 

The standard first-line treatment for schizophrenia — a complex, polygenic mental health disorder — is an antipsychotic medication. But less than half of the patients who receive antipsychotics initially respond well to them, according to the study authors, and some experts believe PGx testing may help patients avoid such trial-and-error prescribing.

However, research exploring the utility of PGx testing in informing treatment for mental health conditions has mostly focused on major depressive disorder, according to the study authors led by Weihua Yue of Peking University Sixth Hospital. Moreover, PGx studies in schizophrenia have been limited to looking at the impact of CYP2D6 and CYP2C19 genes. 

In this study, researchers considered the role of a broader array of PGx genes in guiding therapy response for schizophrenia patients. "In our study, patients treated with MPGT [or multigenetic pharmacogenomics-guided treatment] responded better to antipsychotic medications but with relevantly lower doses," the study authors wrote. "To our knowledge, this study is the first [randomized clinical trial] to evaluate the therapeutic efficacy of MPGT in Chinese Han patients with schizophrenia."

In the study, patients in the PGx-guided care arm provided a cheek swab, which Shanghai-based healthcare firm Conlight Medical conducted genotyping on using Agena's MALDI-TOF-based MassArray system.

Conlight tested for 26 variants across 11 genes associated with response to antipsychotics and recommended drugs based on an algorithm that assigned weighted values to each variant. Investigators included eight commonly prescribed antipsychotics in their analysis.

For example, certain variants in the CYP1A2 gene have been found to affect how a patient metabolizes clozapine, and mutations in the MC4R gene have been linked with adverse events in patients taking quetiapine.

For the first week of study participation, all patients received a low-dose treatment of an antipsychotic prescribed by their doctor as the PGx report was being prepared. After one week, patients in the PGx arm received antipsychotics as recommended by the report, while patients in the standard care arm continued to receive medications based on their doctor's clinical judgment.

Investigators found that patients who received PGx-guided care had greater symptom improvement after six weeks as measured on the Positive and Negative Syndrome Scale (PANSS), which tracks symptom severity in schizophrenia. The scale ranges from 30 to 210 points, with higher scores representing more severe symptoms.

Patients who got PGx-guided care, on average, experienced a 74.2 percent change in their PANSS score after six weeks compared to a 64.9 percent change for those who received standard care. At week 12, the percent change was 83.5 percent and 76.1 percent in the two arms, respectively.

After six weeks, the PGx-guided care arm also had a higher response rate on medications compared to the standard care arm, 82.3 percent versus 64.9 percent, respectively. At 12 weeks, rates of symptomatic remission were 62.8 percent for the PGx-guided care group and 45.4 percent for the standard care group.

Patients reported no severe adverse events during the trial.

"The results of our research support that pharmacogenomic testing aids in selecting optimal medications and has the potential to improve the treatment efficacy for schizophrenia," Yue wrote in an email. "Nevertheless, we acknowledge that there are still many barriers to the application of pharmacogenomic testing in the field of psychiatry."

For example, there are multiple commercial PGx panels on the market testing for different sets of genetic loci. "Standardization of testing panels and interpretation methods remains an area that requires further exploration," she said. And "genome-wide association studies (GWAS) have greatly expanded the field of pharmacogenomics. Therefore, the content of testing also needs to be continually updated to reflect these advancements, and relevant validation studies need to be continually conducted."

In addition, prior PGx studies have tended to focus on schizophrenia patients who relapsed on treatment rather than first-episode patients. This study included patients with first-episode or relapsed schizophrenia, and the researchers reported exploratory analysis suggesting that patients in these subgroups seemed to benefit similarly from PGx testing. However, the study did not consider cost-effectiveness or long-term benefits of PGx testing.

"Our results may suggest the utility of pharmacogenomic testing in patients with first-episode schizophrenia," the study authors wrote. "However, factors such as cost-effectiveness should be considered in this condition, and as the sample with first-episode schizophrenia was relatively small in our study, the result should be interpreted with caution."