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 side effects and requires careful dose titration. This dose is significantly lower than the standard adult starting dose due to age-related changes in metabolism and increased sensitivity to side effects in older adults, as noted in studies such as 1. Gradual titration is essential, with dose increases of 10-25 mg every 1-2 weeks as tolerated, generally not exceeding 40 mg per day in elderly patients, as suggested by 1. Close monitoring is necessary for side effects such as orthostatic hypotension, anticholinergic effects (dry mouth, constipation, urinary retention), sedation, and cardiac conduction abnormalities, which are more pronounced in older adults. Some key points to consider when prescribing nortriptyline to geriatric patients include:

• Nortriptyline has a more favorable side effect profile compared to other tricyclic antidepressants in geriatric patients due to fewer anticholinergic and hypotensive effects, as mentioned in 1.
• Blood level monitoring may be helpful, with therapeutic levels typically between 50-150 ng/mL, as noted in 1.
• Careful consideration of drug interactions is important as many elderly patients take multiple medications that could interact with nortriptyline. It's also important to note that, according to 1, older adults are at significantly greater risk of adverse drug reactions compared with younger populations, and therefore lower starting doses are often recommended. Additionally, secondary-amine TCAs like nortriptyline are thought to be safer than tertiary-amine TCAs due to their lower affinity for muscarinic receptor antagonism, as mentioned in 1.

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.