Individualized insights to guide and monitor pharmacotherapy   

Optimizing outcomes for complex mood disorders

Major depressive disorder (MDD) and associated mood syndromes are among the most common mental health disorders and a continually expanding burden on health care 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. This answer, however, is different for every patient.

By the numbers


million adults in the U.S. are affected by mood disorders1

$326 Billion

economic burden in the U.S. to treat MDD in 2018 2


of patients affected by MDD do not respond to pharmacotherapy 3

Personalizing care through precision medicine

Understanding if a patient is affected by genetic variations 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.

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 cost of care.4 For optimal outcomes, both PGx and therapeutic drug monitoring must be interpreted in the full context of a patient’s clinical picture, including demographic and clinical characteristics.

Beyond the test result

When you partner with Mayo Clinic Laboratories, you extend your network to include some of the world’s leading genetic experts, toxicologists, and laboratory scientists. Our integration with the clinical practice at Mayo Clinic ensures our testing is informed and supported by Mayo Clinic physicians who are part of one of the nation’s top-ranked psychiatric hospitals. Mayo Clinic clinicians, laboratorians, and genetic counselors are available to discuss testing options, interpret results, or help with case review and coordination.

Twenty-four hours a day, seven days a week, our physicians and scientists are available to answer questions and provide support on test ordering and result interpretation.

Comprehensive genotyping for psychotropic medications

PSYQP | Psychotropic Pharmacogenomics Gene Panel, Varies

  • Multi-gene panel that identifies genetic variation in genes known to be associated with response and/or risk of toxicity with psychotropic medications.
  • Examines 23 genes (141 alleles) used to assess approximately 80 medications.

Single gene-genotyping for tricyclic antidepressants and selective serotonin reuptake inhibitors5,6

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

  • Singe-gene assessment useful for identifying patients who may be at risk for altered metabolism of drugs metabolized by cytochrome P450 2D6.
  • Determines the exact genotype and identifies novel variants that may interfere with drug metabolism.

2C19R | Cytochrome P450 2C19 Genotype, Varies

  • Singe-gene assessment useful for identifying patients who may be at risk for altered metabolism of drugs metabolized by cytochrome P450 2C19.

Carbamazepine response and hypersensitivity monitoring7

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 those who are at significant risk through HLA-B*15:02 and HLA-A*31:01 genotyping is recommended.

Known drug-gene associations

  • The variant allele HLA-B*15:02 is strongly associated with 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 greaterrisk 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 antidepressants8

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.

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

VENLA | Venlafaxine, Serum

  • Useful for monitoring serum concentrations during therapy to evaluate potential 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 comedications, dose or formulation changes, and in assessing compliance.

CITAL | Citalopram, Serum

  • Identifies states of altered drug metabolism when used alone or in conjunction with CYP2C19 genotyping.

PARO | Paroxetine, Serum

  • Identifies states of altered drug metabolism when used alone or in conjunction with CYP2D6 genotyping.

Therapeutic drug monitoring for mood stabilizers

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.

A Test in Focus

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.

Learn how to order these tests at your institution.


  1. NIMH » Major Depression (
  2. 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. 10.1007/s40273-021-01019-4
  3. Undurraga J, Baldessarini RJ. Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review. Neuropsychopharmacology. 2012;37:851–64.
  4. Benitez J, Cool C, Scotti D. Use of combinatorial pharmacogenomic guidance in treating psychiatric disorders. Per Med. 2018 Sept. 15(6), 481–494. 10.2217/pme-2018-0074 (
  5. Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017 Jul; 102:1, 37-44. TCA 2016 (
  6. Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015 Aug; 98:2, 127-134. 25974703 (
  7. Phillips E, Sukasem C, Whirl-Carrillo M, et al. Clinical pharmacogenetics implementation consortium guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 update. Clin Pharmacol Ther. 2018 March. CPIC HLA CBZ OXC (
  8. Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology. Pharmacopsychiatry. 2018;51. 9-62.