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Well established

Trazodone and phenobarbital

Phenobarbital both induces CYP3A4 (lowering trazodone levels over time) and adds direct sedative effects — a combination with two separate interaction mechanisms.

Editorially reviewed
Key points
  • Reduces trazodone levels through CYP3A4 induction
  • Also adds direct sedative/CNS-depressing effects
  • Two separate interaction mechanisms in one combination

Phenobarbital is a strong CYP3A4 inducer and also has its own significant sedative, CNS-depressing effect. Combined with trazodone, this creates two separate interaction concerns: reduced trazodone effectiveness over time, and additive sedation in the short term. Both should be discussed with the prescribing clinician.

Not medical advice. Always tell your prescriber and pharmacist about every medication, supplement, and substance you use so they can check for interactions specific to your situation.

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