What is the appropriate dosing of Nortriptyline (tricyclic antidepressant) for the treatment of depression?

From the Guidelines

Nortriptyline should be initiated at a dose of 10 mg at bedtime and gradually increased to a maximum dose of 40 mg per day, given twice daily, with a therapeutic blood level target of 50-150 ng/mL, as this dosing strategy has been shown to balance efficacy and tolerability in the treatment of depression. The dosing of Nortriptyline for depression is crucial for achieving optimal therapeutic effects while minimizing adverse effects. According to the guidelines for managing Alzheimer's disease, which also discuss the use of tricyclic antidepressants like Nortriptyline for depression 1, the initial dosage should be 10 mg at bedtime, with a maximum dosage of 40 mg per day. This approach is supported by the fact that Nortriptyline tends to be more sedating than some other tricyclic antidepressants, making it useful in patients with agitated depression and insomnia. Key considerations in the management of depression with Nortriptyline include:

• Starting with a low dose to assess tolerance and gradually increasing as needed and tolerated
• Monitoring for therapeutic effects, which may take 2-4 weeks to fully develop
• Being aware of potential side effects such as dry mouth, constipation, urinary retention, blurred vision, and sedation due to its anticholinergic properties
• Considering blood level monitoring, with the understanding that therapeutic levels generally fall between 50-150 ng/mL, although more recent guidelines suggest a range of 70-170 ng/mL for Nortriptyline 1
• Ensuring patient safety by monitoring for suicidal thoughts, especially during the initial treatment period or when changing doses, and advising against abrupt discontinuation to prevent withdrawal symptoms. Given the potential for variability in patient response and the importance of balancing efficacy with tolerability, the dose of Nortriptyline should be adjusted based on clinical response and blood levels, with the goal of achieving a therapeutic level while minimizing side effects.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Nortriptyline hydrochloride is not recommended for pediatric patients. Nortriptyline hydrochloride is administered orally in the form of an oral solution. Lower than usual dosages are recommended for elderly patients. The use of lower dosages for outpatients is more important than for hospitalized patients who will be treated under close supervision The physician should initiate dosage at a low level and increase it gradually, checking the clinical response carefully and noting any evidence of intolerance. Following remission, maintenance medication may be required for a longer period of time at the lowest dose that will maintain remission. If a patient develops minor side effects, the dosage should be reduced The drug should be discontinued promptly if adverse effects of a serious nature or allergic manifestations occur. Usual Adult Dose 25 mg 3 or 4 times daily; dosage should begin at a low level and be increased as required. As an alternate regimen, the total daily dose may be given once a day When doses above 100 mg daily are administered, plasma levels of nortriptyline should be monitored and maintained in the optimum range of 50 to 150 ng/mL. Doses above 150 mg per day are not recommended. Elderly Patients 30 to 50 mg/day in divided doses. Plasma Levels Optimal responses to nortriptyline have been associated with plasma concentrations of 50 to 150 ng/mL Higher concentrations may be associated with more adverse experiences. Plasma concentrations are difficult to measure, and physicians should consult with the laboratory professional staff. Larger plasma concentrations of the active nortriptyline metabolite 10-hydroxy nortriptyline have been reported in older patients In one case, such a condition was associated with apparent cardiotoxicity despite the fact that nortriptyline concentrations were within the "therapeutic range." Clinical findings should predominate over plasma concentrations as primary determinants of dosage changes.

The appropriate dosing of Nortriptyline for the treatment of depression is:

• Usual Adult Dose: 25 mg 3 or 4 times daily, with dosage starting at a low level and increasing as required.
• Alternate Regimen: Total daily dose may be given once a day.
• Elderly Patients: 30 to 50 mg/day in divided doses.
• Maximum Recommended Dose: 150 mg per day.
• Optimal Plasma Concentration: 50 to 150 ng/mL 2. Key considerations include:
• Starting with a low dose and gradually increasing as needed and tolerated.
• Monitoring plasma levels when doses exceed 100 mg daily.
• Clinical findings should guide dosage changes rather than plasma concentrations alone.

From the Research

Dosing of Nortriptyline for Depression

• The appropriate dosing of Nortriptyline for the treatment of depression is somewhat vague, with guidelines recommending a fairly wide dose range 3.
• One study initiated Nortriptyline treatment with a 75- to 125-mg dose depending on weight, and found that 81% of patients reached therapeutic drug levels by the end of Week 1 3.
• Another study titrated patients up to full target doses of Nortriptyline within 1 week, with target blood levels of 100 ng/mL, and found that approximately 40% of patients responded to treatment after 6 weeks 4.
• In elderly patients, a daily dose of 50 mg was prescribed, with a range of 20-100 mg, to achieve a steady-state concentration within the range of 50-150 micrograms 5.
• Studies have also shown that plasma levels of Nortriptyline are correlated with therapeutic response, with optimal response occurring at levels between 50 and 139 ng/ml 6, 7.
• Patients with plasma levels within this range had a better response to treatment, as measured by the Hamilton Score, Zung Score, and percent recovered 6, 7.