switching antidepressant (SSRIs to tricyclic antidepressants (TCAs) other than clomipramine) in adults

Last edited 03/2023 and last reviewed 03/2023

Switching to dosulepin requires specialist advice and should not be done in primary care due to the increased cardiac risk and toxicity in overdose.

From all except fluoxetine, fluvoxamine and paroxetine

Cross-taper

• cross-tapering, starting with a low dose TCA can generaly be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability

From fluoxetine

Taper, washout and switch

• gradually reduce the dose of fluoxetine to 20mg daily and stop; wait 4 to 7 days before starting low dose TCA
• clinicians should decide the duration of the washout period on a case-by-case basis

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 TCAs. There is therefore a risk of raised TCA levels in the body when switching.

Fluoxetine may still cause medicine interactions 5 or 6 weeks after stopping, as fluoxetine and its active metabolite have a long half-life.

From fluvoxamine

Cross-taper

• cross-tapering, starting with a low dose TCA can generally be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability. It could include:
  • gradually reducing the dose of fluvoxamine
  • then adding the low dose TCA
  • then stopping fluvoxamine after 4 to 7 days. Clinicians should decide the duration of the washout period on a case-by-case basis.

• alternatively, gradually reduce the dose of fluvoxamine and stop; wait for a period before starting low dose TCA
• clinicians should decide the duration of the washout period on a case-by-case basis

• if switching from fluvoxamine, caution is required because it is a potent inhibitor of the liver enzyme CYP1A2 which is involved in the metabolism of TCAs.
  • there is therefore a risk of raised TCA levels in the body when they are administered together

From paroxetine

Cross-taper

• cross-tapering, starting with a low dose TCA can generally be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability. It could include:
  • gradually reducing the dose of paroxetine to 10mg daily
  • then adding the low dose TCA
  • then stopping paroxetine after 4 to 7 days. Clinicians should decide the duration of the washout period on a case-by-case basis.

• alternatively, gradually reduce the dose of paroxetine and stop; wait for a period before starting low dose TCA
• clinicians should decide the duration of the washout period on a case-by-case basis

• if switching from paroxetine, caution is required because it is a potent inhibitor of the liver enzyme CYP2D6 which is involved in the metabolism of TCAs
  • there is therefore a risk of raised TCA levels in the body when they are administered together

Reference:

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