Jennifer Tovar, PharmD & Hanna M. Schultze, MD, DE, EMBA
Pharmacogenomics: Rethinking Mental Health. How might pharmacogenomics (PGx) reshape the treatment paradigm for mental health disorders? Mental health PGx is a rapidly evolving field at the intersection of psychiatry, genetics, and pharmacology. Psychiatry has traditionally used a trial-and-error method for prescribing due to variable drug responses, often leading to inefficacy or side effects despite guideline adherence. The implications of PGx guidelines, neurotransmitter activity, and polygenes should be carefully considered in the context of genetic variability.
Patients showed greater symptom improvement, remission rates, and medication response with PGx. The credibility of PGx guidelines in enhancing patient outcomes has been supported by research, including the Genomics Used to Improve Depression Decisions (GUIDED) trial (Greden et al., 2019). In this randomized controlled trial, more than 1,100 patients suffering from treatment-resistant depression were randomized to receive either PGx-guided treatment or standard care. Findings revealed that individuals showed greater symptom improvement, remission rates, and medication response when PGx testing guided their medication adjustments, compared to those receiving standard care.
Neurotransmitter-associated genes also influence drug efficacy. Genetic polymorphisms in neurotransmitter-related genes also influence drug efficacy. Variants in the serotonin transporter gene (SLC6A4) impact SSRI effectiveness, while DRD2 variants affect antipsychotic response and side effect profiles (Stein et al., 2021). Additionally, epigenetic factors add another layer of complexity (Zhou et al., 2021). By considering genetic and epigenetic factors, healthcare providers can tailor medications to each patient’s unique biological makeup, potentially improving outcomes and reducing side effects.
Polygenic risk scores explain up to 13.7% of treatment response variability in BPD. Polygenes are genes which, individually, produce negligible effects, but in groups, facilitate phenotypic changes. Emerging research focuses on polygenic risk scores, which aggregate multiple genetic markers to predict treatment outcomes more accurately than single-gene approaches. Findings from one systematic review indicate a greater relevance of polygenic scores in bipolar disorder (BPD), as their combination with clinical variables was shown to explain up to 13.7% of the variance in treatment response. This predictive value is higher in BPD than in other psychiatric conditions (Sharew et al., 2024).
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