What psychotropic medications should a patient with specific genetic profiles or medical conditions avoid, and which medications are they a poor or fast metabolizer for?

Psychotropic Medication Considerations Based on Metabolizer Status

Without specific genetic testing results for this patient, I cannot definitively identify which medications they are poor or fast metabolizers for, but I can provide guidance on which psychotropic medications require metabolizer status consideration and which should be avoided in specific genetic contexts.

General Principles for Metabolizer Status

CYP2D6 Poor Metabolizers (5-8% of Caucasians)

Poor metabolizers of CYP2D6 require dose reductions for many psychotropic medications to avoid excessive drug exposure and adverse effects. 1, 2

Medications requiring caution or dose adjustment in CYP2D6 poor metabolizers include:

• Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine, doxepin, clomipramine) - therapeutic drug monitoring (TDM) is strongly recommended 1
• SSRIs: Paroxetine and fluoxetine are significantly affected 1, 3
• Venlafaxine and mirtazapine require monitoring 1
• Atomoxetine - failing to identify CYP2D6 status before initiating therapy can lead to excessive drug exposure and adverse effects 2
• Antipsychotics: Haloperidol, quetiapine, and risperidone 1
• Clozapine - dose reduction may be necessary as concentrations may be increased 4

CYP2D6 Ultrarapid Metabolizers (1-7% of Caucasians)

Ultrarapid metabolizers may require higher doses to achieve therapeutic effect or may experience treatment failure at standard doses. 1

• These patients metabolize CYP2D6 substrates too quickly, resulting in subtherapeutic plasma concentrations 1
• Consider alternative medications not metabolized by CYP2D6 or use TDM to guide dosing 1

CYP2C19 Metabolizer Considerations

Poor Metabolizers

• Citalopram and escitalopram are primarily metabolized by CYP2C19 1, 5
• Dose adjustments may be necessary to avoid excessive concentrations 6

Ultrarapid Metabolizers

• May experience subtherapeutic concentrations of citalopram, escitalopram, and other CYP2C19 substrates 6

Medications to Avoid in Specific Clinical Contexts

Brugada Syndrome or Cardiac Conduction Abnormalities

Some psychotropic medications can trigger ventricular fibrillation and sudden cardiac arrest in patients with Brugada syndrome and should be avoided. 1

• Consult www.brugadadrugs.org for comprehensive list of contraindicated psychotropic medications 1
• Fever, cocaine, and excessive alcohol also trigger arrhythmias in these patients 1

Drug Interactions Requiring Avoidance

When patients are on rifamycins (rifampin, rifabutin, rifapentine), several psychotropic medications have substantially decreased concentrations and should be avoided or require dose increases. 1

Affected psychotropic medications include:

• Nortriptyline - TDM recommended; may require dose increase or alternative medication 1
• Haloperidol and quetiapine - clinical monitoring required; may need dose increase or alternative 1
• Benzodiazepines (diazepam, triazolam), zolpidem, and buspirone - may require dose increase or alternative 1

Practical Recommendations for Clinical Use

When to Consider Genetic Testing

Genotyping for CYP2C19 and CYP2D6 should be considered when there are side effects or inefficacy of psychotropic medications. 6

Specific situations warranting testing include:

• Suspected noncompliance with unclear cause 1
• Lack of clinical response despite adequate dosing 1
• Adverse effects despite use of generally recommended doses 1
• Children, adolescents, and elderly patients (>65 years) 1
• Patients with hepatic or renal insufficiency 1, 4

Therapeutic Drug Monitoring Strategy

When metabolizer status is unknown or confirmed as poor/ultrarapid, therapeutic drug monitoring provides critical guidance for dose optimization. 1

• TDM is mandatory for lithium for safety reasons 1
• TDM is strongly recommended for tricyclic antidepressants in all patients, especially those with suspected metabolizer abnormalities 1
• Steady-state concentrations should be measured (typically after 5 half-lives) 1

Common Pitfalls to Avoid

• Do not assume standard dosing is appropriate without considering metabolizer status - this can lead to toxicity in poor metabolizers or treatment failure in ultrarapid metabolizers 1, 2
• Do not ignore FDA labeling - several psychotropic medications (citalopram, aripiprazole, atomoxetine, carbamazepine) have pharmacogenetic information in their FDA-approved product inserts 7
• Do not discontinue effective therapy based solely on genotype - clinical response and tolerability take precedence over genetic predictions 6, 8
• Do not use combinatorial pharmacogenetic panels without understanding their limitations - evidence is strongest for single-gene effects on specific medications 7

Algorithm for Clinical Decision-Making

1. Assess patient factors: Age, hepatic/renal function, concomitant medications, prior treatment response 1, 4
2. Consider genetic testing if: treatment failure, intolerable side effects, or high-risk populations 6, 7
3. If poor metabolizer identified: Start with 50% of standard dose or choose alternative medication not metabolized by affected enzyme 2, 4
4. If ultrarapid metabolizer identified: Consider higher doses with TDM guidance or alternative medication 1
5. Implement TDM for tricyclics, lithium, and when metabolizer status suggests risk 1
6. Monitor clinically for efficacy and adverse effects regardless of genetic information 1, 6