Treatment of Treatment-Resistant Depression in Older Adults

Introduction to Tricyclic Antidepressants

The American Academy of Family Physicians recommends nortriptyline or desipramine as the best tricyclic antidepressants for treatment-resistant depression in older adults, with nortriptyline being the preferred first choice due to its established therapeutic plasma level range and favorable side effect profile 1
Secondary amine tricyclics (nortriptyline and desipramine) are superior to tertiary amine TCAs (amitriptyline, imipramine) due to significantly lower anticholinergic activity and reduced risk of orthostatic hypotension, cardiac effects, and urinary retention 1, 2

Tertiary amine TCAs like amitriptyline and imipramine are considered potentially inappropriate medications in older adults per the American Geriatric Society's Beers Criteria due to significant anticholinergic adverse effects 1
Secondary amine TCAs have lower affinity for muscarinic receptor antagonism, making them safer while maintaining equivalent antidepressant efficacy 1, 2

If the TCA trial at therapeutic plasma levels for 4-8 weeks produces partial response but not remission, augmentation with lithium should be the next step rather than switching to another antidepressant, as recommended by the American Psychiatric Association 3, 4
Lithium augmentation of TCAs has well-established efficacy in treatment-resistant depression, with therapeutic lithium blood levels ranging from 0.6-1.0 mEq/L for augmentation 4

The American Academy of Family Physicians advises against using tertiary amine TCAs (amitriptyline, imipramine) as first-line agents in patients over 50 years old 1