This document discusses treatment-resistant depression and provides strategies for managing it. Treatment-resistant depression is defined as failing to respond to adequate trials of two antidepressants or one antidepressant and electroconvulsive therapy (ECT). Left untreated, it can lead to reduced quality of life, relationship and economic problems, increased physical health issues, and even suicide. Effective management of treatment-resistant depression involves thoroughly reviewing the diagnosis and treatment history, ensuring medication compliance, continuing or changing antidepressant medications, adding augmentative therapies like mood stabilizers or ECT, and considering psychosurgery in severe cases.

1. An approach to treatment-resistant depression
Definition:
Failure to respond to adequate (dose and duration i.e. max. dose for at least 6
weeks) courses of 2 antidepressants, or 1 antidepressant and ECT.
The consequences of resistant depression include:
1) Reduced quality of life.
2) Excessive strain on relationships (which may lead to break-up of families).
3) Significant personal economic impact.
4) Increased physical comorbidity (e.g. malignancy, cardiovascular disease,
even premature death).
5) Increased risk of suicide.
6) Therapeutic alienation (making further interventions difficult due to
difficulties forming a therapeutic alliance).
7) High use of psychiatric services (without clear benefit).
Differentiating "treatment resistance":
It is important to distinguish actual treatment resistance from chronicity of
symptoms.
Apparent treatment failure may also occur due to:
1. Incorrect initial diagnosis (i.e. not depressive disorder).
2. Inadequate initial treatment.
3. Poor compliance.
4. Incomplete formulation (esp. role of maintaining factors).
5. Comorbidity (both physical and other psychiatric disorders).

2. Risk factors for treatment resistance:
o Concurrent physical illness.
o Drug/alcohol abuse.
o Personality disorder.
o Delayed treatment.
o High premorbid neuroticism.
Management:
i. Review diagnostic formulation: Is diagnosis correct?, Are there any
unaddressed maintaining factors (e.g. social, physical, psychological)?
ii. Check patient understanding and compliance: (serum levels may help).
iii. Continue monotherapy at maximum tolerable dose: May mean
exceeding dose guidelines (esp. if there has been partial benefit).
iv. Consider change in antidepressant: Try a different class of antidepressant.
v. Consider augmentation with a mood stabiliser: (e.g. lithium).
vi. Consider additional augmentative agents: (e.g. L-tryptophan, T3).
vii. Consider combining antidepressants from different classes: Caution is
advised, due to possible serious adverse reactions (e.g. serotonin syndrome).
viii. Consider use of ECT: (esp. if severe biological features or psychotic
symptoms).
ix. Consider possibility of psychosurgery.