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.
From all except fluoxetine, fluvoxamine and paroxetine
- 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.
Taper, washout and switch
- 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
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