management of resistant depression

Last reviewed 01/2018

Managed at Step 4 of NICE guideline regarding depression management (i.e. by mental health specialists including crisis teams).

Summary points concerning management:

• combined psychological and drug treatment
  • the combination of antidepressant medication with CBT should be considered
  • for patients with treatment-resistant moderate depression who have relapsed while taking, or after finishing, a course of antidepressants, the combination of antidepressant medication with CBT should be considered
• drug treatments
  • a trial of lithium augmentation should be considered for patients whose depression has failed to respond to several antidepressants and who are prepared to tolerate the burdens associated with its use
    • an ECG should be carried out before carrying out lithium augmentation
  • if venlafaxine has not been used before, it should be considered for patients whose depression has failed to respond to two adequate trials of other antidepressants. Consideration should be given to increasing the dose up to 'British National Formulary' limits if required, provided patients can tolerate the side effects
  • augmenting an antidepressant with another antidepressant should be considered for patients whose depression is treatment resistant and who are prepared to tolerate the side effects - there is evidence for benefits from the addition of mianserin or mirtazapine to SSRIs
    • where patients are treated with one antidepressant augmented by another, careful monitoring of progress and side effects is advised and the importance of this should be explained to the patient. Particular care should be taken to monitor for serotonin syndrome
    • when used to augment another antidepressant, mianserin should be used with caution, particularly in older adults, because of the risk of agranulocytosis
    • where combinations of antidepressants other than mianserin with SSRIs and mirtazapine with SSRIs are considered, healthcare professionals should re-evaluate the adequacy of previous treatments carefully before proceeding, and consider seeking a second opinion. Any discussion should be documented in the notes
  • phenelzine should be considered for patients whose depression has failed to respond to alternative antidepressants and who are prepared to tolerate the side effects and dietary restrictions associated with its use. However, its toxicity in overdose should be considered when prescribing for patients at high risk of suicide
  • augmentation of an antidepressant with carbamazepine, lamotrigrine, buspirone, pindolol, valproate or thyroid supplementation is not recommended in the routine management of treatment-resistant depression
  • dosulepin should not be initiated routinely because evidence supporting its tolerability relative to other antidepressants is outweighed by the increased cardiac risk and toxicity in overdose
  • there is insufficient evidence to recommend the use of benzodiazepine augmentation of antidepressants
  • when a patient's depression has failed to respond to various strategies for augmentation and combination treatments, referral to a clinician with a specialist interest in treating depression should be considered
  • with respect to atypical depression:
    • phenelzine should be considered for women whose depression is atypical, and who have not responded to, or who cannot tolerate, an SSRI
      • toxicity in overdose should be considered when prescribing for patients at high risk of suicid
      • patients receiving phenelzine require careful monitoring (including taking blood pressure) and advice on interactions with other medicines and foodstuffs, and should have their attention drawn to the product information leaflet

For more detailed information consult the full guidance (1).

Reference:

1. NICE (April 2007). Management of depression in primary and secondary care.