Prescribing antidepressants according to a patient’s genetic makeup could help manage depressive symptoms in the long-term, a clinical trial suggests.
The findings, in JAMA Network Open, suggest pharmacogenetic guidance could have extended benefits, which may not be apparent early on.
Primary results did not indicate that genotype-guided SSRI treatment was better than usual care at three months in A Depression and Opioid Pragmatic Trial in Pharmacogenetics (ADOPT PGx).
However, significantly more patients receiving genotype-guided therapy achieved the secondary endpoint of depression remission at six months.
“Although outcomes were similar early in treatment, differences emerged over time,” noted Kathryn Blake, PharmD, from Nemours Center for Pharmacogenomics and Translational Research in Jacksonville, Florida, and colleagues.
“These findings suggest a possible longer-term clinical benefit and indicate that future studies should focus on evaluating the durability and long-term impact of genotype-guided prescribing in the management of depressive symptoms.”
SSRIs are the most common pharmacotherapy for depression and variants in cytochrome P450 enzymes CYP2D6 and CYP2C19 can affect their metabolism, influencing exposure to this medication.
Indeed, guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) provide recommendations for SSRI prescribing when genotype information is available.
However, most psychiatry experts and practice guidelines for treating depression have not yet endorsed pharmacogenetic-informed therapy, citing insufficient evidence.
ADOPT PGx was a set of three randomized clinical trials, designed to test whether routine use of pharmacogenetic testing improves medication response among patients with depression, acute pain, or chronic pain.
The ADOPT PGx Depression trial included 221 children and 1239 adults, aged eight years or older who had experienced depression for three months or longer.
A total of 692 patients (47.4%) had an actionable phenotype, of whom 351 (50.7%) were assigned to the intervention, and 341 (49.3%) to usual care.
Among this group, two-thirds reported having depressive symptoms for more than two years, and three quarters were female. The vast majority were on pharmacologic treatment, at 87.1%, with just over half receiving nonpharmacologic treatment.
Participants were randomly assigned to genotype-guided SSRI prescribing or usual care to examine whether pharmacogenetic guidance improves depression over six months.
At three months, there were no significant differences between the intervention and usual care groups in the primary endpoint of change in Patient-Reported Outcomes Measurement Information System (PROMIS) depression T scores among patients with an actionable phenotype.
At this timepoint, there were also no differences in the secondary outcome of adverse effect severity.
However, another secondary endpoint of depression remission according to a PROMIS depression T-score of 16 or less was more likely with the intervention than usual care, at 48.3% (153 of 317 patients) versus 39.4%. (122 of 310 patients).
Based on this, the authors proposed: “These findings suggest that pharmacogenetic testing, including evaluation for CYP2D6 enzyme inhibition (phenoconversion), may offer meaningful benefit with longer follow-up.”
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