Doxepin (Sinequan)

  • Half-life: 3.5 hours
  • The time to peak concentration (Tmax) of doxepin at 6 mg is about 3.5 hours after oral administration in fasting individuals
    • The Tmax is delayed by approximately an additional 3 hours if doxepin is taken with a high-fat meal.
    • Thus, it is recommended that doxepin be taken without food, to minimize the risk of next day sedation, given it is possible for the Tmax to be as long as 6 hours after taking it.[1]
  • Insomnia (middle insomnia, doses of 3 to 6 mg qHS in Canada)[2]
  • Best used for the short-term treatment of maintenance (middle) insomnia, not initial insomnia
  • Doxepin is highly histaminergic and often used as a reference standard in drug comparison studies when looking at histaminergic activity.
    • Doxepin is the most potent antihistamine of the tricyclic antidepressants, with 4x the potency of amitriptyline and 800x the potency of diphenhydramine at the H1 receptor.[3]
  • Doxepin has no anticholinergic effects, which makes it a relatively “safe” sleep aid