MAOI (monoamine oxidase inhibitor), irreversible

Parnate (tranylcypromine) Withdrawal

Parnate (tranylcypromine) has a discontinuation pattern similar to Nardil but with more amphetamine-like properties (tranylcypromine has structural similarity to amphetamines). Some patients describe a stimulant-like crash when stopping in addition to the gradual MAO normalization.

By Dr. Ben Soffer, DO — board-certified physician, at-home ketamine therapy in Florida and New Jersey.

Half-life

~2-4 hours (but enzyme inhibition persists ~2 weeks).

Withdrawal timeline

Onset— 1-7 days after the last dose

Acute symptoms (fatigue, crash) can emerge within days; MAO normalization is gradual.

Peak— Week 1-3

Fatigue and any returning depression peak in the first 3 weeks.

Resolution— 4-6 weeks

Most patients return to baseline within a month or two.

Common symptoms

  • Fatigue (often pronounced)
  • Sleep disturbance
  • Return of depression
  • Mood changes
  • Headache

Less common

  • Vivid dreams
  • Mild anxiety

Tapering guidance

  • A typical taper reduces by 10 mg every 1-2 weeks.
  • Same 14-day washout consideration before starting most other antidepressants.
  • Coordinate the taper with the prescribing physician.

Where ketamine therapy fits

Same caution as Nardil. MAOIs require additional clinical oversight when combined with ketamine. Discuss with both prescribing physicians before starting ketamine therapy on Parnate.

Check ketamine therapy eligibilityMedication safety with ketamine

Frequently asked questions

Why is Parnate withdrawal more fatiguing than Nardil?

Tranylcypromine has structural similarity to amphetamines and some stimulant-like activity. When stopped, some patients describe a stimulant-like crash with pronounced fatigue, in addition to the gradual return of MAO function.

Can I do ketamine therapy on Parnate?

MAOIs require additional caution with ketamine. Discuss specifically with both your prescribing physician and a ketamine-prescribing physician before starting.

Important: This page is informational and does not constitute medical advice or a recommendation to start, stop, or change any medication. Tapering psychiatric medications should always be coordinated with the prescribing physician. Compounded ketamine for anxiety, depression, PTSD, and chronic pain is not FDA approved.

Browse all medication withdrawal guides.