Mental health: Swapping between medicines

Last updated: Monday, April 29, 2024


Antidepressants may need to be changed for a variety of reasons including lack of efficacy or adverse effects. Swapping between them can involve a balance of minimising the risk of a drug interaction while ensuring that the patient has adequate levels of antidepressant on board during the period of changeover. Interactions may be pharmacodynamic or pharmacokinetic in nature.

  • Pharmacodynamic interactions may arise if the two antidepressants act upon the same neurotransmitter(s). For example swapping between two agents that increase serotonin levels can exacerbate the adverse effects of both, and, in some cases, lead to ‘serotonin syndrome’. It is usually rapid in onset, occurring within the first few doses of the second drug. You can read more about this potential side effect here.          

  • Pharmacokinetic interactions may arise through effects on cytochrome p450. For example, some of the SSRIs are potent inhibitors of CYP2D6 (e.g. fluoxetine), which is involved in the metabolism of tricyclic antidepressants. Concomitant use can lead to increased plasma levels of the tricyclic and increased risk of adverse reactions (e.g. dry mouth, sedation, confusion) and potential toxicity. The inhibition of CYP2D6 can persist for some time after stopping an SSRI, so an interaction with a tricyclic antidepressant is still possible even when an SSRI has been discontinued. To avoid such interactions, cross-tapering regimens are sometimes recommended. However these aren’t always appropriate – for example if the patient is suffering a severe adverse reaction, then the causative antidepressant should be discontinued immediately.

For further information on swapping between antidepressants, including cross-tapering regimens, refer to the Information sources.

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Questions about changing antipsychotic drugs occur less frequently than for antidepressants, but they present similar problems with regard to interactions and loss of symptom control. Several strategies have been proposed and are outlined clearly in Information sources such as Bazire’s Psychotropic Drug Directory and The Maudsley Prescribing Guidelines and so will not be repeated here. Studies comparing these techniques are lacking, so when recommending a strategy consider:

  •  The individual patient concerned (e.g. the indication for switching, ability to manage a complex cross-tapering regime if being treated at home, their clinical condition).

  •  The medicines involved (e.g. risk of interactions, side effect profile, half-life, risk of discontinuation symptoms). 

Remember that long-acting depot formulations may remain in the body for several weeks after being stopped. Concomitant prescription of anticholinergic medicines such as procyclidine used for extrapyramidal side effects may no longer be required with a new antipsychotic and can be gradually tapered.