What are the considerations for using Tricyclic Antidepressants (TCAs) in older adults?

From the Guidelines

The use of Tricyclic Antidepressants (TCAs) in older adults requires careful consideration due to their potential for adverse effects, particularly anticholinergic effects and cardiovascular risks 1.

Key Considerations

• Medications such as amitriptyline, imipramine, and nortriptyline are commonly used in this population, but at lower doses, typically starting at 10-25mg per day, and gradually increased as needed and tolerated 1.
• Secondary-amine TCAs (e.g., nortriptyline, desipramine) are thought to be safer due to their lower affinity for muscarinic receptor antagonism, resulting in fewer anticholinergic effects 1.
• The maximum recommended dose is often lower in older adults, typically not exceeding 100mg per day, due to the increased risk of sudden cardiac death associated with higher doses 1.
• Treatment duration is usually long-term, lasting several months to years, with regular monitoring for efficacy and adverse effects.
• An electrocardiogram should be carried out before initiating TCA therapy, especially in patients with a history of cardiovascular disease, and caution should be taken if there is prolongation of the PR or QTc interval 1.

From the FDA Drug Label

Geriatric Use Clinical experience has not identified differences in responses between elderly and younger patients In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic function, concomitant disease and other drug therapy in elderly patients. Geriatric patients are particularly sensitive to the anticholinergic side effects of tricyclic antidepressants including amitriptyline hydrochloride Peripheral anticholinergic effects include tachycardia, urinary retention, constipation, dry mouth, blurred vision, and exacerbation of narrow-angle glaucoma. Central nervous system anticholinergic effects include cognitive impairment, psychomotor slowing, confusion, sedation, and delirium. Elderly patients taking amitriptyline hydrochloride may be at increased risk for falls Elderly patients should be started on low doses of amitriptyline hydrochloride and observed closely

Geriatric Use Confusional states following tricyclic antidepressant administration have been reported in the elderly Higher plasma concentrations of the active nortriptyline metabolite, 10-hydroxynortriptyline, have also been reported in elderly patients Lower than usual dosages are recommended for the elderly patients

The considerations for using Tricyclic Antidepressants (TCAs) in older adults include:

• Dose selection: should be cautious, usually starting at the low end of the dosing range, due to decreased hepatic function, concomitant disease, and other drug therapy in elderly patients 2
• Anticholinergic side effects: geriatric patients are particularly sensitive to these effects, which include:
  • Peripheral effects: tachycardia, urinary retention, constipation, dry mouth, blurred vision, and exacerbation of narrow-angle glaucoma
  • Central nervous system effects: cognitive impairment, psychomotor slowing, confusion, sedation, and delirium 2
• Increased risk of falls: elderly patients taking TCAs may be at increased risk for falls 2
• Confusional states: have been reported in the elderly following TCA administration 3
• Higher plasma concentrations: of active metabolites have been reported in elderly patients 3
• Lower dosages: are recommended for elderly patients 3

From the Research

Considerations for Using Tricyclic Antidepressants (TCAs) in Older Adults

• The use of tricyclic antidepressants (TCAs) in older adults should be limited due to anticholinergic adverse effects 4
• TCAs should also be avoided in elderly persons at high risk of cardiovascular events due to a risk of cardiac arrhythmia 4
• Emerging evidence suggests that SSRIs also have arrhythmogenic potential, and both TCAs and SSRIs should be used cautiously in elderly persons at risk of falls 4
• The tertiary amine tricyclic antidepressants (TCAs) tend to produce significant side-effects in the elderly, but nortriptyline, desipramine, and lofepramine are better tolerated than other TCAs 5
• Nortriptyline is the tricyclic that has been the most studied and should be recommended as an antidepressant for older patients due to its favorable side effect profile and established therapeutic range for its steady-state plasma level 6

Dosage Considerations

• It is recommended to reduce by one half the dosages of tricyclic antidepressants for patients over 65 years of age to avert the occurrence of side-effects 7
• However, the systematic prescription of half-dose tricyclics runs the risk of infratherapeutic dosage, and it is preferable to resort to blood level dosage and to look for a maximum dose tolerance before concluding ineffectuality 7
• The need for a lower dose in the elderly is less certain for the secondary amine TCAs 5

Safety and Harms

• The associations with adverse outcomes were significantly different between the classes of antidepressant drugs, with SSRIs associated with the highest adjusted hazard ratios for falls and hyponatraemia, and the group of other antidepressants associated with the highest hazard ratios for all-cause mortality, attempted suicide/self-harm, stroke/TIA, fracture, and epilepsy/seizures 8
• TCAs did not have the highest hazard ratio for any of the outcomes, but the risks of prescribing antidepressants need to be weighed against the potential benefits of these drugs 8