Advice for all antidepressants

You should read our advice for all antidepressant switching for the treatment of depression before applying that to the individual selective serotonin reuptake inhibitor (SSRI) 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 SSRIs

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

Agomelatine

From all except fluvoxamine

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 discontinuation reactions from stopping the SSRI.

Additional caution when switching from fluoxetine

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

Taper, washout and switch

Gradually reduce the dose of fluvoxamine and stop; wait 4 days before starting agomelatine.

Cross-tapering is not appropriate with this switch because fluvoxamine is a potent inhibitor of the liver enzyme CYP1A2 which is involved in the metabolism of agomelatine. There is therefore a risk of raised agomelatine levels in the body when they are administered together.

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. There 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.

Deciding on the switching strategy

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

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. There is therefore a risk of raised clomipramine levels in the body when they are administered together.

Mirtazapine

Cross-taper

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

Additional caution when switching from fluoxetine

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

Additional caution when switching from fluvoxamine

Start mirtazapine at a dose of 15mg daily. This caution is required because fluvoxamine is a potent inhibitor of the liver enzyme CYP1A2 which is involved in the metabolism of mirtazapine. There is therefore a risk of raised mirtazapine levels in the body when they are administered together.

Moclobemide

Taper, washout and switch

For any SSRI, 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 moclobemide.

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

From all except fluoxetine and sertraline

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

From fluoxetine

After stopping fluoxetine, wait 5 to 6 weeks before starting moclobemide. 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.

From sertraline

After stopping sertraline, wait 7 to 13 days before starting moclobemide. The manufacturer advises a 7 day washout period but 13 days may be considered to account for the long half-life of sertraline’s active metabolite. 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 SSRI, you should gradually reduce the dose and stop. You will then need to wait for a period (see below), dependent on the antidepressant being switched from, 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 fluoxetine

After stopping the SSRI, wait 7 to 14 days before starting the MAOI.

From fluoxetine

After stopping fluoxetine, wait 5 to 6 weeks before starting the MAOI.

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

Another SSRI

From all except fluoxetine

Direct switch

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

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 SSRI. 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.

Serotonin and noradrenaline reuptake inhibitors (SNRIs)

From all except fluoxetine

Direct switch

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

Additional caution when switching from paroxetine

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 duloxetine and venlafaxine. There is therefore a risk of raised duloxetine or venlafaxine levels in the body when they are administered together.

Additional caution when switching from fluvoxamine

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 duloxetine. There is therefore a risk of raised duloxetine levels in the body when they are administered together.

From fluoxetine

Taper, washout and switch

Gradually reduce the dose of fluoxetine to 20mg daily and stop; wait 4 to 7 days before starting the SNRI. 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 duloxetine and venlafaxine. There is therefore a risk of raised duloxetine or venlafaxine levels in the body when switching.

Trazodone

Cross-taper

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

Additional caution when switching from fluoxetine or paroxetine

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 or paroxetine, caution is required as they are potent inhibitors of the liver enzyme CYP2D6 which is involved in the metabolism of trazodone. There is therefore there is a risk of raised trazodone levels in the body when they are administered together.

Tricyclic antidepressants (TCAs) other than clomipramine

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 usually 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 usually 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.

Taper, washout and switch

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.

Deciding on the switching strategy

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

Additional caution

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 usually 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.

Taper, washout and switch

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.

Deciding on the switching strategy

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

Additional caution

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.

Vortioxetine

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

From all except fluoxetine

Direct switch

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

Taper, washout and switch

Alternatively, gradually reduce the dose of the SSRI 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.

Additional caution when switching from paroxetine

If switching from paroxetine, caution is required because paroxetine is a potent inhibitor of the liver enzyme CYP2D6 which is involved in the metabolism of vortioxetine. There is therefore a risk of raised vortioxetine levels in the body when they are administered together.

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 vortioxetine.

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 vortioxetine. There is therefore there is a risk of raised vortioxetine levels in the body when switching.

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
• Tricyclics to other antidepressants: switching in adults

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