Genotype-Guided Antidepressant Prescribing

PATHCHAT Edition No. 91
Published: September 2024
Please contact your local Ampath pathologist for more information.

Authors:

• Dr. Janin Alant
• Dr. Devina Govender
• Kammy Hutheram

Transforming the Management of Depression and Anxiety with Pharmacogenomic Testing

✅ Challenges in Antidepressant Therapy

• Less than half of patients respond to a first-line antidepressant.
• One-third of patients do not respond or tolerate two or more subsequent antidepressant trials.
• Each trial takes 4–8 weeks to assess effectiveness, prolonging untreated illness.
• Trial-and-error prescribing leads to:
  • Increased side effects.
  • Poor treatment adherence.
  • Higher healthcare costs.

✅ Genetic Influence on Antidepressant Response

• Variations in three key pharmacogenes (CYP2D6, CYP2C19, CYP2B6) affect antidepressant metabolism.
• Drugs affected include:
  • Selective serotonin reuptake inhibitors (SSRIs).
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs).
  • Tricyclic antidepressants (TCAs).

📌 Pharmacogenomic testing (PGxT) personalizes medication selection, improving treatment success and reducing side effects.

Pharmacogenomic Testing: A Precision Medicine Approach

✅ How Pharmacogenomic Testing Works

• Identifies individual genetic variations affecting drug metabolism.
• Guides antidepressant selection and dosing adjustments.
• Improves treatment outcomes by reducing side effects and increasing adherence.

✅ Clinical Implementation

• Standardized guidelines from the Clinical Pharmacogenomics Implementation Consortium (CPIC).
• Genotype-based dosing guidelines available for 14 commonly prescribed antidepressants.
• Endorsed by multiple international pharmacology and psychiatry societies.

📌 Pharmacogenomic testing provides evidence-based recommendations for antidepressant prescribing.

Personalizing Antidepressant Dosing and Selection Based on Genetic Variation

✅ How Genetic Variation Affects Drug Response

• Individuals are classified into four metabolizer types:
  • Normal metabolizers: Respond to standard doses.
  • Poor metabolizers: Higher risk of drug accumulation and side effects.
  • Intermediate metabolizers: Increased risk of side effects at standard doses.
  • Ultra-rapid metabolizers: Require higher doses or alternative medications.

📌 Genetic testing ensures the right antidepressant is prescribed at the right dose for each patient.

Pharmacogenomic Testing at Ampath

✅ Comprehensive Genetic Testing

• Ampath’s PGx120 panel tests for:
  • CYP2D6
  • CYP2C19
  • CYP2B6
• Includes all clinically relevant variants recommended by the Association for Molecular Pathology (AMP).
• Focuses on alleles prevalent in sub-Saharan African populations.

✅ Sample & Turnaround Time

• Sample Type: Buccal swab or EDTA blood sample.
• Turnaround Time: 10 working days.

📌 Ampath provides rapid and comprehensive pharmacogenomic testing to optimize antidepressant therapy.

Clinical Evidence Supporting PGx-Guided Antidepressant Prescribing

✅ Meta-Analysis Findings (2024)

• Patients receiving genotype-guided antidepressant therapy were:
  • 41–78% more likely to achieve remission.
  • 20–49% more likely to respond to treatment.

✅ Cost-Effectiveness of PGxT

• PGxT reduces healthcare costs by:
  • Decreasing adverse drug reactions.
  • Minimizing drug switches and dose adjustments.
  • Reducing hospitalizations and emergency visits.
  • Shortening time to remission.
• Canadian simulation study predicted savings of CAD 956 million over 20 years.

📌 Genotype-guided prescribing improves patient outcomes and reduces long-term healthcare costs.

CPIC Dosing Guidelines for Antidepressants

✅ Key Drugs with Genotype-Based Guidelines
✔ Selective Serotonin Reuptake Inhibitors (SSRIs):

• Citalopram
• Escitalopram
• Fluvoxamine
• Paroxetine
• Sertraline
• Vortioxetine

✔ Tricyclic Antidepressants (TCAs):

• Amitriptyline
• Clomipramine
• Doxepin
• Desipramine
• Imipramine
• Nortriptyline
• Trimipramine

✔ Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):

• Venlafaxine

📌 CPIC guidelines provide detailed recommendations for dose adjustments based on genetic test results.

Conclusion

✅ Pharmacogenomic testing revolutionizes antidepressant prescribing by:

• Optimizing drug selection and dosing.
• Reducing side effects and treatment failure.
• Improving adherence and clinical outcomes.
• Lowering healthcare costs by preventing unnecessary drug switches and hospitalizations.

✅ Testing Availability at Ampath

• Pharmacogenomic testing for CYP2D6, CYP2C19, and CYP2B6 is available as part of the PHARMA panel.
• Results provided within 10 working days.
• For more information, contact: pgx@ampath.co.za.

📌 Pharmacogenomic testing enables personalized, evidence-based antidepressant therapy, improving patient care and quality of life.