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Monoamine oxidase inhibitors

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Monoamine oxidiase inhibitors (MAOI)s are a class of antidepressants that help brain neurotransmitters remain active longer, which may lead to a reduction in symptoms of depression (1).

MAOIs are used much less frequently than tricyclic antidepressants and related antidepressants, or SSRIs and related antidepressants because of the dangers of drug and dietary interactions.

They may be more useful in the treatment of atypical depression, for example when the patient is overeating, oversleeping, or oversensitive to criticism, with sustained depression of mood.

The therapeutic effects of MAOI may take more than 3 weeks to appear and at least 6 weeks may be necessary for maximal response. Replacement by a tricyclic must not start earlier than 2 weeks after discontinuation of an MAOI otherwise serious drug interactions may appear.

Prescription of an MAOI should be undertaken by, or in consultation with, specialist psychiatric services (1).

MAOI discontinuation syndrome

  • reactions to MAOI discontinuation, particularly those reported with tranylcypromine, tend to be more severe than with other antidepressants (2)
    • features may include:
      • (i) a worsening of depressive symptoms, exceeding the severity of the state that originally led to treatment
      • (ii) an acute confusional state with disorientation, paranoid delusions and hallucinations
      • (iii) anxiety symptoms, including hyperacusis and depersonalisation

Using a washout period (no antidepressant prescribed)

  • is essential when switching to and from MAOIs because of the risk of drug interactions that can lead to serotonin syndrome

Summary guidance regarding switching to or from an MAOI states (4):

  • Care is required when switching between antidepressants.
  • When switching between monoamine-oxidase inhibitor (MAOI) or moclobemide (a reversible inhibitor of monoamine-oxidase type A- RIMA) and other antidepressants, the first antidepressant agent should be withdrawn gradually and discontinued before starting the second antidepressant
  • For switches that involve a MAOI, a washout period is always advised
  • Patients should be assessed on an individual basis to determine how quickly the switch can be made by assessing history of discontinuation reactions, concurrent medication and severity of depression
  • The potential for medication errors should be considered.


  1. NICE (2004). Management of depression in primary and secondary care.
  2. Anderson IM et al (2000). Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. J Psychopharmacol; 14: 3-20.
  3. Haddad PM, Anderson IM. Advances in Psychiatric Treatment 2007; 13: 447-457
  4. NHS Specialist Pharmacy Service (April 2019). How do you switch between monoamine oxidase inhibitors and SSRI, tricyclic or related antidepressants?

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