What is the effect of Tegretol (carbamazepine) 800 mg orally (po) every morning (qam) and 400 mg po every night (qhs) on trazodone 450 mg po qhs levels?

Carbamazepine Significantly Reduces Trazodone Levels by 75-80%

Carbamazepine 1200 mg daily reduces trazodone 450 mg to an approximate equivalent of 90-110 mg (approximately 24% of the original dose) due to enzyme induction. This significant drug interaction requires dose adjustment to maintain therapeutic efficacy.

Mechanism of Interaction

Carbamazepine is a potent inducer of hepatic CYP3A4 and other cytochrome P450 enzymes 1. This enzyme induction significantly accelerates the metabolism of trazodone, leading to:

• Decreased plasma concentrations of both trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP)
• Reduction of trazodone levels to approximately 24% of pre-carbamazepine values after 4 weeks of co-administration 2
• Reduction of m-CPP levels to approximately 40% of pre-carbamazepine values 2

Clinical Implications

Reduced Efficacy

• The 450 mg trazodone dose is effectively reduced to approximately 90-110 mg when combined with carbamazepine 1200 mg daily
• This reduction is likely to significantly diminish trazodone's therapeutic effects, whether used for depression or insomnia

Dosing Considerations

• If trazodone is being used for insomnia, the typical dose range is 25-100 mg at bedtime 3
• For antidepressant effects, trazodone is typically dosed at 150-300 mg for full efficacy 4
• The patient's current effective dose (after carbamazepine's effect) may be insufficient for antidepressant effects but potentially still effective for sleep

Management Options

1. Dose Adjustment:

   • To maintain equivalent therapeutic effect, trazodone dosage would need to be increased approximately 4-fold
   • However, this approach has limitations due to potential side effects at very high doses

2. Medication Alternatives:

   • Consider alternative medications with less interaction potential
   • For insomnia, non-benzodiazepine BZRAs might be more appropriate as they have better evidence for efficacy than trazodone 5
   • For depression, medications less affected by carbamazepine induction might be preferable

3. Monitoring:

   • If continuing this combination, close monitoring for reduced trazodone efficacy is essential
   • Symptoms of depression or insomnia may worsen due to this interaction

Caveats and Considerations

• The FDA drug label specifically lists trazodone among medications whose levels are decreased by carbamazepine 1
• The interaction is well-documented and clinically significant 6
• This interaction affects both trazodone and its active metabolite m-CPP 2
• The American Heart Association notes that trazodone may potentially induce CYP450 enzymes 3, but this effect is overwhelmed by carbamazepine's much stronger enzyme induction

Conclusion

For this 24-year-old female on carbamazepine 1200 mg daily and trazodone 450 mg at bedtime, the carbamazepine is reducing the effective trazodone dose to approximately 24% of its original level (around 90-110 mg). This reduction is likely to significantly impact the therapeutic efficacy of trazodone, particularly if it's being used for its antidepressant effects rather than solely for sleep.