Advice for all antidepressants

You should read our advice for all antidepressant switching for the treatment of depression before applying that to the individual tricyclic antidepressant (TCA) switches below.

• Establishing if a person needs to switch their antidepressant
• Considerations when choosing an alternative antidepressant
• Planning and agreeing an antidepressant switching strategy
• Monitoring a person during and after antidepressant switching

Specific advice when switching from TCAs

Strategies for switching from TCAs to other antidepressants are outlined below.

Our page on Switching strategies for antidepressants contains further information on the available strategies.

Agomelatine

Cross-taper

Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability.

There is limited experience with this switch so extra caution is required. Although interactions are not expected, agomelatine is not expected to mitigate withdrawal reactions from stopping TCAs.

Mirtazapine

Cross-taper

Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability.

Moclobemide

Taper, washout and switch

For any TCA, you should gradually reduce the dose and stop. You will then need to wait for a period, dependent on the drug being switched from (see below), before starting moclobemide.

Cross-tapering is not recommended due to the high risk of serotonin syndrome.

From TCAs other than clomipramine

After stopping the TCA, wait 7 days before starting moclobemide.

From clomipramine

After stopping clomipramine, wait 7 to 21 days before starting moclobemide. The manufacturer for clomipramine suggests a washout period of 21 days whereas other sources suggest shorter periods. Clinicians should decide the duration of the washout period on a case-by-case basis.

Monoamine oxidase inhibitors (MAOIs)

Switching to an MAOI is always a complex switch and you should follow specialist advice.

Taper, washout and switch with specialist advice

For any TCA, you should gradually reduce the dose and stop. You will then need to wait for a period, dependent on the antidepressant being switched from (see below), before starting the MAOI. The specialist will advise the duration of the washout period on a case-by-case basis taking into consideration the MAOI being started.

Cross-tapering is not recommended due to the high risk of serotonin syndrome.

From all except clomipramine and imipramine

After stopping the TCA, wait 7 to 21 days before starting low dose MAOI.

From clomipramine or imipramine

After stopping clomipramine or imipramine, wait 21 days before starting low dose MAOI.

Selective serotonin reuptake inhibitors (SSRIs)

From all except clomipramine

Cross-taper

Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability. It could include:

• halving the dose of the TCA
• then adding the SSRI at the usual starting dose
• then slowly reducing and stopping the TCA over 5 to 7 days

Additional caution when switching to fluoxetine, fluvoxamine and paroxetine

If switching to fluoxetine, fluvoxamine or paroxetine, caution is required because fluvoxamine is a potent inhibitor of the liver enzyme CYP1A2 and fluoxetine and paroxetine are potent inhibitors of the liver enzyme CYP2D6; these enzymes are involved in the metabolism of TCAs. Although the TCA is being withdrawn, you should still be aware of the risk of raised TCA levels in the body when they are administered together.

From clomipramine

Taper, stop and switch

Gradually reduce the dose of clomipramine and stop. Start low dose SSRI the following day. If switching to fluoxetine it should be started at 10mg daily.

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.

TCAs to serotonin and noradrenaline reuptake inhibitors (SNRIs)

From all except clomipramine

Cross-taper

Cross-tapering starting with a low dose SNRI can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability.

From clomipramine

Taper, stop and switch

If switching from clomipramine, gradually reduce the dose of clomipramine and stop. Start low dose SNRI the following day.

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.

Trazodone

Cross-taper

Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability. It should include:

• halving the dose of the TCA
• then adding trazodone
• then slowly reducing and stopping the TCA

Another TCA

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 clomipramine

Direct switch

A direct switch, i.e. stopping one medicine and then starting the new medicine the following day, is normally possible.

From clomipramine

Cross-taper

Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability.

Vortioxetine

There is limited experience with this switch so extra caution is required to avoid serotonin syndrome.

From all except clomipramine

Cross-taper

Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability. It should include:

• halving the dose of the TCA
• then adding vortioxetine
• then slowly reducing and stopping the TCA

Taper, washout and switch

Alternatively, gradually reduce the dose of the TCA and stop; wait for a period before starting vortioxetine. Clinicians should decide the duration of the washout period on a case-by-case basis.

Deciding on the switching strategy

Our guidance on Planning and agreeing an antidepressant switching strategy will help you decide which switching strategy to choose.

From 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

If switching from clomipramine, gradually reduce the dose of clomipramine and stop. Start low dose vortioxetine the following day.

Taper, washout and switch

Alternatively, gradually reduce the dose of clomipramine and stop; wait for a period before starting vortioxetine. Clinicians should decide the duration of the washout period on a case-by-case basis.

Deciding on the switching strategy

Our guidance on Planning and agreeing an antidepressant switching strategy will help you decide which switching strategy to choose.

More advice on individual switches

We have further advice on how to switch between individual antidepressants of different types. Browse our collection below.

• MAOI to other antidepressants: switching in adults
• Moclobemide to other antidepressants: switching in adults
• Trazodone to other antidepressants: switching in adults
• Vortioxetine to other antidepressants: switching in adults
• SNRIs to other antidepressants: switching in adults
• Agomelatine to other antidepressants: switching in adults
• Mirtazapine to other antidepressants: switching in adults
• SSRIs to other antidepressants: switching in adults

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