Drug Interaction Between Celexa (Citalopram) and Metoprolol
Citalopram increases metoprolol plasma levels approximately 2-fold through CYP2D6 inhibition, which may reduce metoprolol's cardioselectivity, but this interaction is generally manageable without dose adjustment in most patients. 1
Mechanism of Interaction
The interaction occurs through hepatic metabolism:
- Citalopram is a weak-to-moderate CYP2D6 inhibitor that interferes with metoprolol's primary metabolic pathway 1, 2
- Metoprolol is predominantly metabolized by CYP2D6, making it susceptible to drugs that inhibit this enzyme 2, 3
- The FDA label specifically documents this interaction, noting a 2-fold increase in metoprolol plasma levels when co-administered with citalopram 40 mg/day for 22 days 1
- Citalopram causes a 2- to 3-fold increase in metoprolol bioavailability, which is less severe than potent CYP2D6 inhibitors like paroxetine (4- to 6-fold increase) or fluoxetine 2, 4
Clinical Significance
The interaction has documented effects but limited clinical consequences:
- The FDA label states that increased metoprolol levels are associated with decreased cardioselectivity, though co-administration had no clinically significant effects on blood pressure or heart rate in controlled studies 1
- Among beta-blockers, metoprolol is classified as having moderate drug interaction potential compared to carvedilol, propranolol, or nadolol 5
- Population-level data from 332,254 older patients showed no significant increase in bradycardia risk when comparing CYP2D6-inhibiting antidepressants (including citalopram) versus non-inhibiting antidepressants in metoprolol users 6
Clinical Management Recommendations
Monitor for beta-blocker adverse effects but routine dose adjustment is not required:
- Check heart rate and blood pressure at baseline and after initiating citalopram, particularly watching for excessive bradycardia (heart rate <50 bpm), hypotension, or dizziness 5
- Monitor for signs of excessive beta-blockade including fatigue, exercise intolerance, cold extremities, or worsening heart failure symptoms 5
- Consider dose reduction of metoprolol only if symptomatic bradycardia or hypotension develops, rather than preemptively 2
- This combination is safer than metoprolol with paroxetine, fluoxetine, or bupropion, which should be avoided due to severe CYP2D6 inhibition and documented cases of severe bradycardia and AV block 2, 4
Important Caveats
The interaction severity depends on patient-specific factors:
- CYP2D6 genetic polymorphism affects interaction magnitude: patients with two fully functional CYP2D6 alleles experience greater increases in metoprolol exposure compared to those with one functional allele 7
- Citalopram doses ≤20 mg/day may produce less interaction than the 40 mg/day dose studied in the FDA label 1
- Elderly patients may be more susceptible to bradycardia from this combination, though population data did not confirm increased hospitalization risk 6
- Alternative antidepressants with minimal CYP2D6 inhibition include sertraline, venlafaxine, mirtazapine, and mianserin if the interaction is problematic 2, 3