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Protriptyline (Vivactil)

TCA • Last reviewed 2025-09-27

General information

Protriptyline is a secondary amine TCA with activating properties due to preferential norepinephrine reuptake inhibition and minimal histamine blockade.

It is sometimes used in patients with prominent daytime fatigue or adjunctively in narcolepsy-related cataplexy.

Therapeutic plasma concentrations range 70–250 ng/mL; higher levels increase cardiac arrhythmia risk.

Because of its activating profile, divided daytime dosing is recommended and insomnia should be monitored.

Dosing & administration

Start 5–10 mg three or four times daily; titrate by 5–10 mg increments every 3–5 days.

Usual effective dose 15–40 mg/day; maximum 60 mg/day.

Reduce dose in hepatic impairment or CYP2D6 poor metabolizers.

Mechanism of action

Blocks norepinephrine reuptake with modest serotonin effect; weak antihistamine activity results in minimal sedation.

Metabolism & pharmacokinetics

Half-life ~54 h; extensive hepatic metabolism (CYP2D6/CYP2C19) with renal elimination of metabolites.

Drug interactions

Avoid MAOIs and serotonergic combinations.

CYP2D6 inhibitors raise levels; enzyme inducers reduce efficacy.

Sympathomimetics and stimulants may potentiate adrenergic effects.

Monitoring & safety checks

  • Therapeutic drug level (70–250 ng/mL)

  • Blood pressure/heart rate during titration

  • Assess for insomnia and agitation

Discontinuation guidance

Taper gradually over ≥4 weeks to avoid cholinergic rebound and relapse.

References

  1. Protriptyline Prescribing Information — DailyMed
  2. Therapeutic drug monitoring of protriptyline — Therapeutic Drug Monitoring (2022)
  3. Use of protriptyline in narcolepsy management — Sleep Medicine (2021)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.