Resuming Nortriptyline After 5-Day Interruption
Resume nortriptyline at the previous maintenance dose immediately without retitration. After a 5-day interruption, nortriptyline plasma levels have declined but not completely cleared, and the patient has already demonstrated tolerance to the therapeutic dose, making retitration unnecessary and potentially harmful by delaying symptom control 1.
Pharmacokinetic Rationale
Nortriptyline has a half-life of approximately 18-44 hours, meaning after 5 days (approximately 3-7 half-lives), plasma concentrations are significantly reduced but the patient's previous dose tolerance remains established 1.
Steady-state therapeutic plasma concentrations (50-150 ng/mL) are typically achieved within 5-7 days of consistent dosing, so resuming at the maintenance dose will restore therapeutic levels within one week 2, 3.
The therapeutic window for nortriptyline is well-established at 50-150 ng/mL, with levels above 150 ng/mL associated with decreased efficacy and increased adverse effects 2, 4.
Clinical Management Protocol
Immediate resumption strategy:
Restart at the exact previous maintenance dose (e.g., if the patient was taking 75 mg nightly, resume 75 mg nightly immediately) 1, 5.
Monitor for orthostatic hypotension during the first 48-72 hours after resumption, as this is the primary cardiovascular concern with tricyclic antidepressants, though risk is lower than with initial titration 5.
Assess for anticholinergic effects (dry mouth, constipation, urinary retention) within the first week, though these should be minimal given prior tolerance 1.
Monitoring timeline:
Evaluate clinical response at 1-2 weeks after resumption to ensure return to baseline symptom control 6.
Most depressive symptoms require 4 weeks of consistent treatment for full therapeutic effect, but patients previously stabilized should show improvement within 1-2 weeks of resuming therapy 6.
Critical Pitfalls to Avoid
Do not retitrate from a low starting dose (e.g., 10-25 mg), as this unnecessarily delays therapeutic benefit and may precipitate symptom relapse in a previously stabilized patient 1.
Do not increase the dose above the previous maintenance level without evidence of inadequate response after 4 weeks, as plasma levels above 150 ng/mL are associated with significantly poorer clinical outcomes 2, 4.
Do not combine with other serotonergic agents during the resumption period without careful monitoring for serotonin syndrome, particularly if the patient is taking other medications 1.
Special Considerations for Elderly Patients
Elderly patients (>65 years) typically require lower doses (mean 50 mg daily, range 20-100 mg) to achieve therapeutic plasma concentrations of 50-150 ng/mL 3.
Nortriptyline is preferred over tertiary amine TCAs (amitriptyline, imipramine) in older adults due to lower anticholinergic burden 1.
Therapeutic outcomes in elderly patients are comparable to or better than younger patients when plasma concentrations are maintained within the therapeutic range 2.
Duration of Continued Treatment
Continue nortriptyline for at least 4-12 months after achieving remission for a first episode of major depression 1.
For recurrent depression (2+ episodes), consider prolonged maintenance therapy (years to lifelong), as the probability of recurrence increases to 70% after two episodes and 90% after three episodes 1.