Mood disorders
Elevating treatment outcomes through precision therapeutics
Major depressive disorder (MDD) and associated mood syndromes, which are estimated to affect more than 21 million individuals in the United States,1 are among the most common mental health disorders and a continually expanding burden on healthcare systems. For patients affected by these complex syndromes, which vary in clinical presentation, timely, effective treatment can have a positive impact on their quality of life. Key to successful outcomes is determining the right psychotropic medication.
Targeted testing for optimized outcomes
Understanding if a patient is affected by genetic variation associated with altered metabolism of certain medications that make them resistant to treatment is integral to guiding treatment selection. Pharmacogenomics (PGx), or genetic testing used to inform medication selection and dosing, has the potential to revolutionize medication selection for individuals with treatment-resistant depression.
Incorporating PGx testing into clinical practice as an adjunct to or in advance of therapeutic drug monitoring (TDM), which quantifies drug concentrations in the blood, provides physicians and psychiatrists with personalized insights to identify and avoid adverse drug reactions. In instances of poor treatment response, PGx facilitates developing individualized treatment plans based on probable medication response. This approach not only maximizes therapeutic efficacy, it minimizes toxicity, improves medication adherence, and lowers overall costs.5 For optimal outcomes, both PGx and TDM must be interpreted in the full context of a patient’s clinical picture, including demographic and clinical characteristics.
Psychotropic PGx panel
Results from our comprehensive panel can increase understanding of an individual’s genetic makeup to help personalize dosing decisions.
Key testing
- PSYQP | Psychotropic Pharmacogenomics Gene Panel, Varies
- Examines 23 genes (141 alleles) used to assess approximately 80 medications.
- Identifies variations in genes known to be associated with response and/or risk of toxicity with psychotropic medications.
Highlights
Ann Moyer, M.D., Ph.D., explains Mayo Clinic Labs’ new focused pharmacogenomics panel, a real-time, PCR-based testing approach that assesses 10 genes known for their drug-gene associations, to provide guidance on medication selection for patients across a variety of specialities.
Single gene testing for SSRIs and TCAs
Inter-individual differences in tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) pharmacokinetic parameters and treatment outcomes are associated with CYP2D6 and CYP2C19 genetic variants. With some drugs being affected by CYP2D6 only (e.g., amitriptyline) and others by both polymorphic enzymes (e.g., clomipramine), focused testing is recommended.
Known drug-gene associations
- SSRIs: citalopram, escitalopram, fluvoxamine, paroxetine, sertraline
- TCAs: amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, trimipramine
Key testing
- 2D6Q | Cytochrome P450 2D6 Comprehensive Cascade, Varies
- Identifies variants in the CYP2D6 gene that might interfere with drug metabolism.
- Determines precise genotype when other testing methods are indeterminate.
- Provides information relevant to tamoxifen, codeine, and tramadol, as well as other medications metabolized by cytochrome P450 2D6.
- 2C19R | Cytochrome P450 2C19 Genotype, Varies
- Identifies variants in the CYP2C19 gene that might interfere with drug metabolism.
Carbamazepine and human leukocyte antigen (HLA) genetic variation
Human leukocyte antigen (HLA) genetic variation is implicated in the development of specific cutaneous adverse reactions to aromatic anticonvulsants. To reduce the incidence of serious, and sometimes fatal, cutaneous adverse reactions to carbamazepine and oxcarbazepine, identifying carbamazepine response and hypersensitivity through HLA-B*15:02 and HLA-A*31:01 genotyping is recommended.5
Known drug-gene associations
- The variant allele HLA-B*15:02 is strongly associated with a greater risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients treated with carbamazepine or oxcarbazepine.
- The variant allele HLA-A*31:01 is associated with a greater risk of maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms, and SJS/TEN in patients treated with carbamazepine.
Key testing
- CARBR | Carbamazepine Hypersensitivity Pharmacogenomics, Varies
- Genotyping of HLA-A*31:01 and HLA-B*15:02 prior to therapy initiation.
Therapeutic drug monitoring for antidepressants
Tricyclic antidepressants (TCAs)
- AMTRP | Amitriptyline and Nortriptyline, Serum
- Useful for monitoring amitriptyline and nortriptyline serum concentrations during therapy to avoid toxicity, especially in children and poor metabolizers of CYP2D6.
- CLOM | Clomipramine, Serum
- Determines whether a poor therapeutic response is attributable to noncompliance or can aid in dose optimization.
- DESPR | Desipramine, Serum
- Useful for evaluating desipramine (Norpramin) toxicity and/or patient compliance.
- DXPIN | Doxepin and Nordoxepin, Serum
- Useful for evaluating doxepin toxicity and patient compliance.
- IMIPR | Imipramine and Desipramine, Serum
- Useful for evaluating imipramine and desipramine toxicity and patient compliance.
- NOTRP | Nortriptyline, Serum
- Useful for evaluating nortriptyline toxicity and patient compliance.
- TRMP | Trimipramine, Serum
- Useful for evaluating trimipramine toxicity and patient compliance.
Select serotonin reuptake inhibitors (SSRIs)
- DULOX | Duloxetine, Serum
- Useful for monitoring serum concentrations during therapy to evaluate potential toxicity and patient compliance.
- FLUOX | Fluoxetine, Serum
- Useful for managing co-medications, dose, or formulation changes, and in assessing compliance.
Highlights
Ann Moyer, M.D., Ph.D., and Paul Jannetto, Ph.D., explain how precision therapeutics can improve treatment for patients with major depressive disorder. The optimal antidepressant medication and dose vary among individuals. Pharmacogenomic testing and therapeutic drug monitoring can guide clinicians to the most-effective treatment for each patient.
Therapeutic drug monitoring for mood stabilizers
Key testing
- CARBG | Carbamazepine-10,11-Epoxide, Serum
- Useful for monitoring patients exhibiting symptoms of carbamazepine toxicity whose total serum carbamazepine concentration is within the therapeutic range, but who may be producing significant levels of the active metabolite epoxide, which can accumulate to concentrations equivalent to carbamazepine.
- CARF | Carbamazepine, Free, Serum
- Useful for monitoring carbamazepine therapy in patients with altered or unpredictable protein binding capacity.
- CARFT | Carbamazepine, Free and Total, Serum
- Useful for monitoring carbamazepine free and total serum levels in uremic patients.
- CARTA | Carbamazepine, Total, Serum
- Measures total carbamazepine levels in serum.
- CARTF | Carbamazepine Profile, Serum
- Measures carbamazepine free, total, and carbamazepine-10,11-epoxide levels in serum.
- LAMO | Lamotrigine, Serum
- Useful for adjusting lamotrigine in patients concurrently prescribed phenytoin, carbamazepine, or valproic acid therapy.
- LITH | Lithium, Serum
- Identifies lithium toxicity.
- VALPF | Valproic Acid, Free, Serum
- Useful for evaluating toxicity and monitoring free valproic acid serum levels.
- VALPG | Valproic Acid, Free and Total, Serum
- Useful for monitoring total and free valproic acid levels in therapy.
References
- NIMH » Major Depression (nih.gov)
- Greenberg P, Fournier A-A, Sisitsky T, et al. The economic burden of adults with major depressive disorder in the United States (2010 and 2018). Pharmacoeconomics. 2021. doi:10.1007/s40273-021-01019-4
- Tansey KE, Guipponi M, Hu X, et al. Contribution of common genetic variants to antidepressant response. Biol Psychiatry. 2013 Apr 1;73(7):679-82. doi:10.1016/j.biopsych.2012.10.030. Epub 2012 Dec 11. PMID: 23237317.
- Undurraga J, Baldessarini RJ. Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review. Neuropsychopharmacology. 2012;37:851–64.
- Benitez J, Cool C, Scotti D. Use of combinatorial pharmacogenomic guidance in treating psychiatric disorders. Per Med. 2018 Sept. 15(6), 481–494. doi:10.2217/pme-2018-0074 (futuremedicine.com).