Comparative Effectiveness of Pharmacogenomics for Treatment of Depression.

Andrew A Nierenberg; Masoud Kamali; Dustin J Rabideau; Jonathan E Alpert; Warren D Taylor; Samantha Pegg; Audrey R Stromberg; Kedie Pintro; Zainab O Soetan; Nur Akpolat; Saee Chitale; Amrutha Garimella; Ingrid R Hsu; Hadi Kobaissi; Louisa G Sylvia

doi:10.1097/jcp.0000000000002175

PubMed · 42572938

Comparative Effectiveness of Pharmacogenomics for Treatment of Depression.

Andrew A Nierenberg·Masoud Kamali·Dustin J Rabideau·Jonathan E Alpert·Warren D Taylor·Samantha Pegg·Audrey R Stromberg·Kedie Pintro·Zainab O Soetan·Nur Akpolat·Saee Chitale·Amrutha Garimella·Ingrid R Hsu·Hadi Kobaissi·Louisa G Sylvia

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Abstract

PURPOSE/BACKGROUND: Pharmacogenomics (PGx), or the use of genetic information to assess drug-gene interactions, is an important step toward precision medicine. It is unclear if clinician use of PGx yields better outcomes for their patients. This study compared the effectiveness of combinatorial PGx-guided plus guideline-informed treatment (PGx+GIT) with guideline-informed treatment (GIT) alone to improve well-being in individuals with major depressive disorder. METHODS/PROCEDURES: Eligible participants (N=201) were randomized to PGx+GIT or GIT alone. PGx was measured with the proprietary GeneSight combinatorial test. PGx+GIT participant clinicians received test results within 2 business days to inform decisions about medication changes. Participants completed the World Health Organization Well-Being Index (WHO-5), Patient Health Questionnaire (PHQ-9), and PROMIS Profile physical functioning and social roles and activity domains every 2 weeks for 2 months and then every 2 months for the remaining 10 months. Monthly medication changes operationalized as necessary clinical adjustments were tracked with the medication recommendation tracking form. FINDINGS/RESULTS: Both groups improved average well-being over the 12-month study period (model-based change in WHO-5 per log (week) [95% CI]: 4.1 [3.3, 5.0] PGx+GIT and 4.8 [4.0, 5.5] GIT). PGx+GIT did not result in superior improvement in well-being (model-based difference [95% CI]: -0.6 [-1.8, 0.5], P =0.270), or any secondary outcomes. The effect of randomized treatment on well-being was not moderated by depression severity, number of previous failed medications for major depressive disorder, or presence of a comorbid condition. IMPLICATIONS/CONCLUSIONS: These data suggest PGx+GIT was not superior to GIT alone, possibly due to a ceiling effect of GIT, or PGx did not yield better results.

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Humans Major Depressive Disorder Pharmacogenetics Female Precision Medicine Male Adult Antidepressive Agents Middle Aged Treatment Outcome Practice Guidelines as Topic depression personalized medicine pharmacogenomics precision medicine Journal Article Randomized Controlled Trial Comparative Study

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Andrew A Nierenberg, Masoud Kamali, Dustin J Rabideau, Jonathan E Alpert, Warren D Taylor, Samantha Pegg, Audrey R Stromberg, Kedie Pintro, Zainab O Soetan, Nur Akpolat, Saee Chitale, Amrutha Garimella, Ingrid R Hsu, Hadi Kobaissi, Louisa G Sylvia. 2026-08-10. Comparative Effectiveness of Pharmacogenomics for Treatment of Depression.. https://doi.org/10.1097/jcp.0000000000002175

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Journal Article; Randomized Controlled Trial; Comparative Study resource Adult subject Antidepressive Agents subject Comparative Study subject Depression subject Female subject Humans subject Journal Article subject Major Depressive Disorder subject Male subject Middle Aged subject Pharmacogenetics subject Randomized controlled trials study

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