Switching strategies available include: (1)
Cross-tapering
Gradually reduce and stop the first antidepressant whilst simultaneously starting the second at a low dose and gradually increasing. Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability.
Direct switching
Direct switches may be possible when antidepressants have similar pharmacology or mode of action. The second antidepressant should alleviate discontinuation symptoms of the first. Stop the first antidepressant and start the second at the usual therapeutic dose the next day.
Taper, stop and switch
Gradually reduce and then stop the first antidepressant; start the second immediately after stopping the first, usually on the next day.
Taper, washout and switch
Gradually reduce the dose of the first antidepressant and stop; wait for a period (the “washout”) before starting the second.
Stop, washout and switch
Stop the first antidepressant; wait for a period (the “washout”), before starting the second.
SSRI SWITCHING
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 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.
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.
Taper, stop and switch
Gradually reduce the dose of the SSRI and stop. Start low dose clomipramine the following day.
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.
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. 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.
After stopping the SSRI, wait 7 days before starting moclobemide.
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.
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.
After stopping the SSRI, wait 7 to 14 days before starting the MAOI.
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
Direct switch
A direct switch, i.e. stopping one antidepressant and then starting the new antidepressant the following day, is normally possible.
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)
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.
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.
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.
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.
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:
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.
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.
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:
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.
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.
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.
TCA SWITCHING
Agomelatine
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-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.
After stopping the TCA, wait 7 days before starting moclobemide.
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.
After stopping the TCA, wait 7 to 21 days before starting low dose MAOI.
After stopping clomipramine or imipramine, wait 21 days before starting low dose MAOI.
Selective serotonin reuptake inhibitors (SSRIs)
Cross-taper
Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability. It could include:
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.
Taper, stop and switch
Gradually reduce the dose of clomipramine and stop. Start a 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)
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.
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:
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.
Direct switch
A direct switch, i.e. stopping one medicine and then starting the new medicine the following day, is normally possible.
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.
Cross-taper
Cross-tapering can usually be undertaken cautiously over 2 to 4 weeks, the speed is determined by individual tolerability. It should include:
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.
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.
Stopping antidepressant treatment
When stopping a person's antidepressant medication: (2)
Reference
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