Philadelphia—Using pharmacogenomic testing can help clinicians avoid prescribing antidepressant medications that might have undesirable outcomes, but a recent study did not find large and persistent effects on symptom remission.

The study involving medical centers across the country and led by the University of Pennsylvania and the Corporal Michael J. Crescenz Veterans Affairs (VA) Medical Center, both in Philadelphia, determined that patients who underwent genetic testing generally had more positive outcomes compared with patients in usual care.

The report in the Journal of the American Medical Association noted that, over 24 weeks of treatment, participants with major depressive disorder (MDD) who received genetic testing had a decline in depressive symptoms with a peak effect at 12 weeks. The researchers advised that although pharmacogenomic testing reduced prescribing of medications with predicted drug-gene interactions, it had only a small and nonpersistent effect on symptom remission.

The lead author, David Oslin, MD, of VA healthcare, suggested that the results might encourage clinicians to consider using pharmacogenomic testing, with patient consent, to help improve treatment decisions.

"The results were not a slam dunk, and in fact, an important outcome of the study is that only about 15% to 20% of the patients had genes that would significantly interfere with the prescribed medication," Dr. Oslin advised. "But I think the results favoring a positive effect on treatment, although small, will encourage providers to test patients and get this genetic information. Future research should explore if there are subgroups of patients who would benefit more from testing."

The background information in the article pointed out that choosing effective antidepressants for the treatment of MDD can be imprecise and that antidepressants have remission rates of about 30% with initial treatment.

To try to improve those rates, researchers conducted a pragmatic, randomized clinical trial that compared treatment guided by pharmacogenomic testing versus usual care. Participants included 676 clinicians and 1,944 patients from 22 VA medical centers who were enrolled from July 2017 through February 2021, with follow-up ending in November 2021. Patients were eligible if they were diagnosed with MDD and were initiating or switching treatment with a single antidepressant. Veterans with active substance use disorder, mania, psychosis, or concurrent treatment with a specified list of medications were excluded.

In the pharmacogenomics-guided group, involving 966 patients, clinicians were provided with results from a commercial pharmacogenomic test. At the same time, the comparison group of 978 veterans received usual care and access to pharmacogenomic results after 24 weeks. The 24-week assessment was completed by 79% of the patients, who had a mean age of 48 years and 25% of whom were women.

The results indicated that the estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59.3%, 30.0%, and 10.7%, respectively, compared with 25.7%, 54.6%, and 19.7% in the usual-care group.

"The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction for no drug-gene vs. moderate/substantial interaction (odds ratio [OR], 4.32 [95% CI, 3.47-5.39]; P <.001) and no/moderate vs. substantial interaction (OR, 2.08 [95% CI, 1.52-2.84]; P = .005) (P <.001 for overall comparison)," the researchers explained. "Remission rates over 24 weeks were higher among patients whose care was guided by pharmacogenomic testing than those in usual care (OR, 1.28 [95% CI, 1.05-1.57]; P  = .02; risk difference, 2.8% [95% CI, 0.6%-5.1%]) but were not significantly higher at week 24 when 130 patients in the pharmacogenomic-guided group and 126 patients in the usual care group were in remission (estimated risk difference, 1.5% [95% CI, -2.4%-5.3%]; P = .45)."

The authors concluded that, among patients with MDD, pharmacogenomic testing for drug-gene interactions reduced prescribing of medications with predicted drug-gene interactions compared with usual care, adding, "Provision of test results had small nonpersistent effects on symptom remission."

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