Considerations when choosing an alternative antidepressant

Published Last updated See all updates

Consider the risks associated with switching an antidepressant for depression, the patient's individual circumstances and when to seek specialist advice.

Establish the need to switch

You should establish the need for an antidepressant switch for the treatment of depression prior to choosing what to switch to.

Appraise the medicines options

To choose an antidepressant to switch to, consider the options available and their characteristics as they relate to the individual’s needs and preferences. Our article on mental health evidence resources may help you. Characteristics to consider include:

Side-effect potential

If any previous side-effects were a class effect, switching to a medicine in the same class may not be appropriate.


Potential interactions will depend on the person’s other medicines and the antidepressants involved in the switch. Some antidepressants can interact in dangerous ways with existing medicines and therefore can’t be used, or you may need to avoid cross-tapering antidepressants. Pharmacodynamic interactions may include serotonin syndrome, hypotension and drowsiness. Pharmacokinetic interactions may, for example, include elevation of tricyclic plasma levels by some selective serotonin reuptake inhibitors (SSRIs).

Previous response

Check the person’s treatment history to identify their response to previous treatment and the antidepressant type.

Understand the person’s individual characteristics

Understand the person’s individual characteristics to be able to match a suitable antidepressant. Consider the following aspects:

Risks of harm

Where self-harm or overdose may be a factor, consider the risks of any new medicines on these aspects.

Co-morbidities and age

Consider existing co-morbidities and the person’s age. For example, previous or current cardiovascular illness or epilepsy may affect the choice of treatment. Older people may be more susceptible to the additive effects of antidepressants.

Pregnancy and breastfeeding

For women of childbearing potential, consider the choice of antidepressant that’s appropriate now and in the future. You may find our articles on the treatment of depression during pregnancy; and the use of SSRIs during breastfeeding and tricyclics during breastfeeding helpful.

Individual needs

A number of other characteristics of the person need to be considered prior to choosing; these include:

The person’s beliefs

Consider the person’s preference for treatment, perception of risks, benefits, and their expectations.

The potential for serotonin syndrome

Serotonin syndrome is an uncommon but potentially serious side effect of most antidepressants. Concomitant or sequential use of antidepressants can increase the risk of serotonin syndrome as most antidepressants increase serotonin levels in the brain.

Serotonin syndrome is more likely in people taking antidepressants who are:

  • taking a dose of a serotonergic antidepressant towards the top of the licensed dose e.g. SSRIs, serotonin and noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs)
  • taking other serotonergic medicines e.g. pethidine, tramadol, fentanyl, ondansetron, metoclopramide and lithium
  • switching from one serotonergic antidepressant to another

The potential for discontinuation symptoms

People may experience discontinuation symptoms from abruptly stopping their antidepressant treatment.

Discontinuation symptoms are more likely in people who have or are on:

  • antidepressant treatment for eight weeks or more
  • an antidepressant dose towards the top of the licensed dose
  • an antidepressant with a short half-life (e.g paroxetine or venlafaxine). The half-life can be found in the summary of product characteristics of the antidepressant.
  • other centrally acting medicines such as certain antihypertensives, antihistamines and antipsychotics
  • experienced symptoms of anxiety at the initiation of antidepressant treatment
  • experienced discontinuation symptoms before

Identify complex switches

Some switches may be particularly high risk and both the choice of medicines to switch to, and the switch itself, should be undertaken with the advice of a mental health specialist. They include switches:

  • for any person under 18 years old
  • to or from an MAOI
  • to or from reboxetine
  • for people who are already on two or more antidepressants
  • for people who have or are suspected of having bipolar disorder
  • for people with chronic depressive symptoms or more severe depression which is affecting their personal and social functioning and that has not responded to treatment in primary care
  • for people who have coexisting psychosocial and/or physical health risk factors

When referring to a specialist, ensure the person and/or the carer understand the next steps in receiving care.

Planning the switch and monitoring

After you’ve established that a switch is necessary and agreed what you’re switching to, you should plan and agree the strategy and monitor as necessary.

Planning and agreeing an antidepressant switching strategy

Guidance on planning and implementing the antidepressant switch after the need and choice of antidepressant have been decided.

Monitoring a person during and after antidepressant switching

Review people at appropriate time points; advise on what to expect and report; and beware of the possibility of discontinuation and serotonin syndromes.

Individual switches

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

Update history

  1. Changed title and summary
  1. Published

Print this page