Best Time of Day to Take Nortriptyline
Nortriptyline should be taken at bedtime as a single daily dose. 1
Rationale Based on Evidence
The guideline evidence consistently recommends 10 mg at bedtime as the initial dosing regimen for nortriptyline 1. This timing recommendation is based on the drug's sedating properties, which can be therapeutically advantageous for patients experiencing insomnia or agitated depression.
Key Pharmacologic Considerations
Nortriptyline tends to be more sedating compared to other tricyclic antidepressants like desipramine 1. This sedative effect makes bedtime dosing optimal because it:
- Minimizes daytime drowsiness and impairment
- Provides therapeutic benefit for patients with concurrent insomnia
- Reduces interference with daily activities and work performance
Dosing Flexibility
While bedtime dosing is preferred, the FDA label indicates that when doses exceed 100 mg daily, the total daily dose may be divided (given twice daily) 2. However, research demonstrates that once-daily bedtime dosing produces comparable steady-state plasma levels to divided dosing throughout the day 3.
A comparative study found that single bedtime dosing at 10 PM versus three-times-daily dosing produced mean plasma levels that were stable and comparable between schedules, with differences less than 30 ng/mL in seven of eight patients—not clinically significant 3.
Clinical Pitfalls to Avoid
Morning dosing should be avoided with nortriptyline. Research comparing morning versus bedtime administration found a higher incidence of drowsiness and medication non-adherence among patients taking nortriptyline in the morning 4. This makes practical sense given the drug's sedating anticholinergic profile.
Practical Implementation
- Start with 10 mg at bedtime (around 10 PM is reasonable based on study protocols)
- Increase by 10-25 mg every 3-7 days as tolerated 1
- Maximum dose of 40 mg per day can be given as a single bedtime dose 1
- If doses above 100 mg daily are needed, consider splitting to twice daily (though this is less common in modern practice) 2
- Maintain therapeutic plasma levels between 50-150 ng/mL 1
The sedating properties that make bedtime dosing optimal are the same characteristics that make nortriptyline particularly useful for patients with agitated depression and insomnia 1. This represents a strategic use of side effects to improve both medication adherence and therapeutic outcomes.