What tricyclic antidepressants (TCAs) are safest in the elderly population?

From the Guidelines

Nortriptyline and desipramine are the safest tricyclic antidepressants (TCAs) for elderly patients due to their lower affinity for muscarinic receptor antagonism and fewer anticholinergic effects. These medications are preferred over other TCAs like amitriptyline or imipramine, which are associated with significant adverse anticholinergic effects and are considered potentially inappropriate medications in the American Geriatric Society’s Beers Criteria 1. When prescribing for elderly patients, it is recommended to start with low doses, typically 10-25 mg of nortriptyline or desipramine at bedtime, and increase gradually while monitoring for side effects.

The target dose is usually lower than for younger adults, often 50-75 mg daily rather than 100-150 mg. Blood level monitoring is recommended, especially for nortriptyline, which has a well-established therapeutic window of 50-150 ng/mL. Despite being "safer" options, all TCAs should be used cautiously in the elderly due to potential side effects, including:

• Orthostatic hypotension
• Sedation
• Confusion
• Urinary retention
• Constipation

A pre-treatment ECG is advisable to check for cardiac conduction abnormalities. TCAs should be avoided in patients with significant cardiac disease, narrow-angle glaucoma, or prostatic hypertrophy. In many cases, selective serotonin reuptake inhibitors (SSRIs) or other newer antidepressants may be preferable first-line options for elderly patients due to their more favorable side effect profiles, as noted in a study comparing commonly used antidepressant medications 1.

From the FDA Drug Label

A case of significant hypoglycemia has been reported after the addition of nortriptyline (125 mg/day) in a type II diabetic patient maintained on chlorpropamide (250 mg/day). Lower than usual dosages are recommended for the elderly patients (see Elderly Patients under DOSAGE AND ADMINISTRATION). Clinical studies of desipramine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients Lower doses are recommended for elderly patients (see DOSAGE AND ADMINISTRATION).

Safest Tricyclic Antidepressants in the Elderly:

• Nortriptyline and desipramine are two tricyclic antidepressants with available information for use in the elderly.
• Both drugs require lower doses in elderly patients due to potential increased risk of adverse reactions, such as confusional states and falls.
• Nortriptyline may have a more predictable pharmacokinetic profile, but desipramine has a similar recommendation for dose reduction in the elderly.
• It is essential to exercise caution and monitor renal function when using these medications in elderly patients, as they may have decreased renal elimination and be more prone to toxic reactions. 2 3

From the Research

Tricyclic Antidepressants in the Elderly

• The safest tricyclic antidepressants in the elderly are a subject of study, with some research suggesting that nortriptyline is a preferred option due to its favorable side effect profile 4.
• Nortriptyline has been shown to have low anticholinergic activity, relatively few cardiac side effects, and relatively less orthostatic hypotension, making it a safer choice for elderly patients 4.
• Desipramine is also considered to have a less toxic side effect profile, although its efficacy has not been as well studied as nortriptyline 4.
• Tertiary amine tricyclics, such as amitriptyline and imipramine, have been reported to be effective in depressed geriatric patients, but their potential for side effects makes them less advisable for use in the elderly 4.

Comparison with Other Antidepressants

• Studies have compared the efficacy and safety of nortriptyline with other antidepressants, such as paroxetine and sertraline, in elderly patients 5, 6.
• One study found that paroxetine and nortriptyline had similar rates of relapse and time to relapse in elderly depressed patients over an 18-month period 5.
• Another study found that sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline in patients 70 and older 6.
• Second-generation antidepressants, such as sertraline, are often preferred for the elderly due to their milder side effects and lower toxicity in overdose 7.

Dosage and Plasma Concentration

• The dosage of nortriptyline in elderly patients can be predicted from plasma concentration at 24 hours after a single 50 mg dose, allowing for more precise and safe treatment 8.
• This prediction test can help prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success 8.