switching antidepressant (SSRIs to clomipramine) in adults

Last edited 03/2023 and last reviewed 03/2023

SSRIs to clomipramine

Cross-tapering is not recommended and should only be undertaken if specialist advice is in place, this is because clomipramine is a potent serotonin reuptake inhibitor so there is a high risk of serotonin syndrome.

• Taper, stop and switch

  • gradually reduce the dose of the SSRI and stop. Start low dose clomipramine the following day

From fluoxetine

Taper, washout and switch

• gradually reduce the dose of fluoxetine to 20mg daily and stop; wait 14 to 21 days before starting low dose clomipramine
  • clinicians should decide the duration of the washout period on a case-by-case basis
• fluoxetine may still cause medicine interactions 5 or 6 weeks after stopping, as fluoxetine and its active metabolite have a long half-life
• if switching from fluoxetine, caution is required as it is a potent inhibitor of the liver enzyme CYP2D6 which is involved in the metabolism of clomipramine
  • is therefore a risk of raised clomipramine levels in the body when switching

From fluvoxamine or paroxetine

Taper, stop and switch

• gradually reduce the dose of fluvoxamine or paroxetine and stop. Start low dose clomipramine the following day.

• alternatively, gradually reduce the dose of fluvoxamine or paroxetine and stop; wait for a period before starting clomipramine. Clinicians should decide the duration of the washout period on a case-by-case basis.

Additional caution

• if switching from fluvoxamine or paroxetine, caution is required because fluvoxamine is a potent inhibitor of the liver enzyme CYP1A2, and paroxetine is a potent inhibitor of the liver enzyme CYP2D6; these enzymes are involved in the metabolism of clomipramine
  • is therefore a risk of raised clomipramine levels in the body when they are administered together

Reference:

• NHS Specialist Pharmacy Service (February 2023). SSRIs to other antidepressants: switching in adults