3 Clinical psychopharmacology3.4 Therapeutics
3.4.2.4 Switching within and across classes
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Written by Resident Doctor Committee · Published
Before switching
Before switching for non-response, confirm the diagnosis, an adequate dose and duration, adherence and drug levels.
Partial response may favour optimisation or augmentation; no benefit or poor tolerability favours a switch.
Four strategies
Strategy | What happens | Favoured when | Main risk |
|---|---|---|---|
Direct switch | Stop one drug, start the other the next day | Similar pharmacology, low interaction risk | Withdrawal, abrupt loss of effect |
Cross-taper | Reduce one drug while introducing the other | Overlap is safe and a gap risks relapse | Additive toxicity |
Taper then switch | Taper to zero, then start the second | Overlap is undesirable | Relapse during the taper |
Taper and washout | Stop, then wait for elimination or enzyme recovery | Overlap would be hazardous | Untreated interval |
Switching antidepressants
Switch | Method | Reason |
|---|---|---|
Selective serotonin reuptake inhibitor (SSRI) to SSRI, such as citalopram to sertraline | Direct: stop one, start the other the next day at a low starting dose | Similar pharmacology |
Different mechanisms, such as sertraline to venlafaxine or trazodone to mirtazapine | Cautious cross-taper | Limits discontinuation symptoms without stacking two full serotonergic doses |
Tricyclic to SSRI | Halve the tricyclic, add the SSRI, then withdraw the tricyclic slowly | SSRIs inhibit cytochrome P450 2D6 (CYP2D6) and raise tricyclic levels; abrupt tricyclic withdrawal causes cholinergic rebound |
Washouts around monoamine oxidase inhibitors
Never cross-taper where a combination with a monoamine oxidase inhibitor (MAOI) is hazardous. Wait for washout instead.
Outgoing drug | Wait before the next drug | Reason |
|---|---|---|
Irreversible MAOI (phenelzine, tranylcypromine) | About 2 weeks before a serotonergic antidepressant | New monoamine oxidase must be synthesised |
Moclobemide, a reversible inhibitor of monoamine oxidase A | 24 hours, for example before sertraline | Inhibition is reversible |
Most SSRIs, such as escitalopram (half-life about 30 hours) | At least 1 week before an irreversible MAOI | Short half-life |
Sertraline | 2 weeks before an irreversible MAOI | Longer washout |
Fluoxetine | At least 5 to 6 weeks before an MAOI | Its metabolite norfluoxetine has a half-life of 1 to 2 weeks |
Residual enzyme inhibition after fluoxetine can call for a lower starting dose of the replacement.
Switching antipsychotics
Aripiprazole has the most consistent trial evidence for improving weight and metabolic measures after a switch from olanzapine.
Introducing aripiprazole can occasionally worsen psychosis, so monitor the transition closely.