Tricyclic antidepressant (TCA), most serotonergic of the TCAs, FDA-approved for OCD

Anafranil (clomipramine) Withdrawal

Clomipramine (Anafranil) has a moderate discontinuation profile that combines TCA cholinergic rebound with SSRI-pattern serotonergic withdrawal, because clomipramine is the most serotonergic of the TCAs. OCD return is the most clinically important phenomenon for patients tapering clomipramine.

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

Half-life

~32 hours for clomipramine; active metabolite ~70 hours.

Withdrawal timeline

Onset— 1-3 days after dose reduction

Symptoms emerge gradually.

Peak— Week 1-2

Symptoms peak in the first 1-2 weeks.

Resolution— 2-4 weeks (discontinuation); OCD return varies

Acute discontinuation symptoms resolve within a few weeks. OCD return is a separate consideration.

Common symptoms

  • Sleep disturbance
  • Vivid dreams
  • Sweating
  • Nausea
  • Headache
  • Anxiety
  • Return of OCD symptoms

Less common

  • Brain zaps
  • Tremor
  • GI distress

Tapering guidance

  • A typical taper reduces by 25 mg every 1-2 weeks. OCD patients often need longer schedules and additional therapy support during transition.
  • Coordinate the taper with the prescribing physician.

Where ketamine therapy fits

Clomipramine can be used with at-home ketamine therapy with closer cardiovascular monitoring. Ketamine is an active area of research for OCD as well as depression, and the conversation about ketamine in a clomipramine context often spans both indications.

Check ketamine therapy eligibilityMedication safety with ketamine

Frequently asked questions

How long does clomipramine withdrawal last?

Acute symptoms resolve within 2-4 weeks. OCD symptom return is a separate consideration and may not align with the discontinuation timeline.

Will my OCD come back if I stop clomipramine?

OCD commonly returns when clomipramine is stopped. Coordinate any taper with the prescribing physician and consider whether bridging strategies (slower taper, additional therapy, alternative medication) are appropriate.

Is clomipramine compatible with ketamine therapy?

Generally yes, with closer cardiovascular monitoring. Ketamine has research evidence in OCD as well as depression.

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.