What is the recommended starting dose of nortriptyline (tricyclic antidepressant) for geriatric patients?

From the Guidelines

The recommended starting dose of nortriptyline for geriatric patients is 10 mg at bedtime, as this population is more susceptible to adverse effects due to age-related changes in metabolism and increased sensitivity to side effects. This dose is supported by the study published in the American Family Physician in 2002 1, which provides guidelines for managing Alzheimer's disease and suggests a starting dose of 10 mg at bedtime for nortriptyline, with a maximum dose of 40 mg per day.

Key Considerations

• The dose can be gradually increased by 10-25 mg every 5-7 days as tolerated, with most elderly patients requiring a total daily dose of 30-50 mg for therapeutic effect.
• Maximum doses should generally not exceed 75 mg daily in geriatric patients.
• Close monitoring is essential during initiation and dose adjustments, particularly for anticholinergic side effects (dry mouth, constipation, urinary retention, blurred vision), orthostatic hypotension, sedation, and cardiac effects.
• Nortriptyline levels should be checked if available, aiming for a therapeutic range of 50-150 ng/mL, as noted in the study published in the American Family Physician in 2002 1.

Rationale

The study published in the Journal of the National Comprehensive Cancer Network in 2010 1 provides information on the use of tricyclic antidepressants, including nortriptyline, for adult cancer pain, but does not specifically address geriatric dosing. However, the study published in the American Family Physician in 2015 1 highlights the importance of using lower starting doses in older adults, approximately 50% of the adult starting dose, due to the increased risk of adverse drug reactions. Given the potential for adverse effects, starting with a low dose of 10 mg at bedtime and titrating slowly is crucial to minimize adverse effects while achieving therapeutic benefit.

From the FDA Drug Label

Lower than usual dosages are recommended for elderly patients. Elderly Patients 30 to 50 mg/day in divided doses. The starting dose of nortriptyline for geriatric patients is 30 to 50 mg/day in divided doses, with the dose initiated at a low level and increased gradually as required and tolerated.

• The dose should be adjusted based on clinical response and tolerance.
• Plasma levels of nortriptyline should be maintained in the optimum range of 50 to 150 ng/mL. 2

From the Research

Nortriptyline Starting Dose in Geriatric Patients

• The starting dose of nortriptyline in geriatric patients can be predicted from the plasma concentration at 24 hours after a single test dose, which helps to prevent toxic plasma concentrations and enhance therapeutic success 3, 4.
• A study used a 25-mg nortriptyline test dose to establish a 24-hour plasma level in 18 physically healthy, moderately depressed, geriatric outpatients, and found that correlations between the 24-hour test dose plasma level and steady state levels were significant for maintenance dosages of 50,75, and 100 mg/day 3.
• Another study found that geriatric patients experienced few subjective side effects of nortriptyline, and the drug produced no clinically significant changes in several parameters of the EKG, but did induce significant orthostatic hypotension in the systolic component 5.
• The mean daily dose of nortriptyline prescribed in geriatric patients was 50 mg (range 20-100 mg), which provided a mean observed steady-state nortriptyline concentration of 104 micrograms/l, with a range of 76-180 micrograms/l 4.
• A case series found that the mean daily dose of nortriptyline was 54 mg, and the mean plasma level was 97 ng/mL, with minor side effects occurring in three patients, and no patients developing significant electrocardiogram changes 6.

Dosage Prediction and Plasma Concentration

• A nomogram was made from the regression equations to predict the dosage required to achieve a steady state concentration within a 50 to 150 ng/ml range 3.
• The plasma concentration at 24 hours after a single 50 mg dose can be used to predict the daily dose required to achieve a steady-state concentration within the range of 50-150 micrograms/l 4.
• The steady-state nortriptyline concentration was found to be within the range of 50-150 ng/ml in most patients, with a mean observed steady-state nortriptyline concentration of 104 micrograms/l 4.

Clinical Response and Side Effects

• The antidepressant therapeutic effects of nortriptyline appeared to be similar in geriatric patients as in younger depressed patients 5.
• Geriatric patients experienced few subjective side effects of nortriptyline, and the drug produced no clinically significant changes in several parameters of the EKG 5.
• Nortriptyline did induce significant orthostatic hypotension in the systolic component, but not in the diastolic component, and the orthostatic hypotension produced by nortriptyline was not greater in geriatric patients than in younger patients treated with the same dose 5.