Prozac, Zoloft, Paxil, Celexa — the drugs have familiar names. Tens of millions of people in the United States take these or other SSRIs (selective serotonin reuptake inhibitors) to treat depression and anxiety disorders. Genetic variants known to slow or speed the metabolism of SSRIs, affecting their efficacy and safety, are very common.
In a national randomized clinical trial reported recently in JAMA Network Open, genotyping indicated that 47% of the trial’s 1,239 adult and 221 child participants bore drug metabolism traits that could change SSRI selection or dosing. The trial’s primary-analysis group included 692 participants with these actionable traits.
Led by researchers at Vanderbilt Health and at Nemours Children’s Health in Jacksonville, Florida, the National Institutes of Health (NIH)-funded trial was conducted through the IGNITE Pragmatic Trials Network.
Participants had experienced depression for three months or longer. Conducted across nine academic and community health systems and designed to test real-world outcomes, the trial provided routine genotype-guided prescribing support for the intervention group: computerized alerts in the electronic health record (EHR); standardized clinical notes with genotype results and prescribing recommendations; and pharmacist consultations. Prescribers were not obligated to follow any guidance received. Usual-care participants had their DNA stored and were genotyped after the study’s six-month follow-up, with results then returned to the EHR.
In terms of its primary outcome, the trial found no difference between the intervention and usual-care groups. At three months from release of genotype results in the EHR for the intervention group, Patient-Reported Outcomes Measurement Information System (PROMIS) depression scores were similar in the two groups.
Depression outcomes measured at six months from baseline were another matter. Remission as measured by PROMIS was 48% in the decision-support group, compared to 39% in the usual-care group.
“Depression is an often devastating and highly costly illness that can be difficult to treat successfully,” said the corresponding author, Josh Peterson, MD, MPH, Professor and Chair of the Department of Biomedical Informatics and Vice President for Personalized Medicine at Vanderbilt Health. “The increase in remission found in the trial should prompt wider interest in genotype-guided prescribing of SSRIs among researchers and clinicians and prompt longer-term studies.”
Previous large, randomized studies of genotype-guided SSRI prescribing were criticized for using commercial proprietary genotype risk algorithms. The new trial used publicly available genotype risk guidance from the Food and Drug Administration and the Clinical Pharmacogenetics Implementation Consortium.
The new study is among three national randomized clinical trials sponsored by the NIH to test whether, in depression, acute pain or chronic pain, routine use of pharmacogenetic testing improves medication response.
“A host of drugs include pharmacogenomic guidance on the label, but testing still isn’t common enough to use that information very often,” Peterson said. “These new trials intend to bring clarity to clinicians and health care payers about whether pharmacogenomics could improve clinical outcomes.”
The study’s lead author is Kathryn Blake, PharmD, of Nemours Children’s Health. Others on the study from Vanderbilt include Michelle Liu, PharmD, Kerri Cavanaugh, MD, MHS, and Sara Block, MS. The study was supported by the NIH under awards U01HG007269, U01HG010232, U01HG010248, U01HG010231, U01HG010245 and U01HG010225.
