Nortriptyline Side Effects
Nortriptyline commonly causes anticholinergic side effects (dry mouth, constipation, blurred vision), somnolence, weight gain, and cardiac effects including QTc prolongation and orthostatic hypotension, though it has fewer anticholinergic effects than amitriptyline. 1
Common Anticholinergic Side Effects
- Dry mouth is the most consistently reported anticholinergic effect, persisting even during long-term maintenance therapy 1, 2
- Constipation occurs due to anticholinergic activity on the gastrointestinal tract 1
- Blurred vision results from anticholinergic effects on pupillary accommodation 1
- Somnolence is prominent, making nortriptyline useful for patients with agitated depression and insomnia 1
- Urinary retention can occur, particularly in elderly patients 3
Cardiovascular Side Effects
- QTc prolongation is a significant concern requiring baseline ECG monitoring before initiating treatment 1
- Orthostatic hypotension occurs but is less frequent than with amitriptyline; only 2 of 26 patients in one study required treatment with fludrocortisone 4
- Tachycardia is consistently observed, with heart rate remaining higher in nortriptyline-treated patients compared to placebo during long-term therapy 2
- Cardiac dysrhythmias can occur, particularly in patients with preexisting cardiac disease, though nortriptyline has relatively fewer cardiac side effects than other tricyclics 5, 6
- Doses >100 mg/day are associated with increased risk of sudden cardiac death, requiring caution in patients with cardiovascular disease 7
Metabolic Effects
- Weight gain is common and may worsen obstructive sleep apnea in susceptible patients 1
Central Nervous System Effects
- Confusion and disturbed concentration can occur, particularly in overdose situations 3
- Drowsiness is frequently reported but may be related to residual depression rather than the medication itself 2
Comparative Tolerability Profile
Nortriptyline has fewer anticholinergic and antihistaminergic effects than amitriptyline, making it the preferred tricyclic for elderly patients 1, 5. This is because nortriptyline has predominantly noradrenergic activity with less cholinergic blockade compared to balanced inhibitors like amitriptyline 7.
Critical Monitoring Requirements
- Baseline ECG is essential to assess QTc interval before starting treatment; if PR or QTc interval is prolonged, nortriptyline should not be used 7, 1
- Therapeutic drug monitoring with target levels of 50-150 ng/mL helps optimize efficacy while minimizing toxicity 1
- Elderly patients require lower starting doses (10 mg at bedtime) due to increased sensitivity to side effects 7, 1
Overdose Manifestations
- Critical manifestations include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma 3
- QRS duration ≥0.10 seconds on ECG is the best indicator of overdose severity 3
- Deaths may occur from overdosage, requiring immediate hospital monitoring and gastrointestinal decontamination 3
Common Pitfalls to Avoid
- Do not use nortriptyline in patients with prolonged QTc interval or recent myocardial infarction 7
- Avoid starting at high doses in elderly patients despite evidence that younger patients tolerate 75-125 mg initial doses 4; elderly require 10 mg starting doses 7
- Do not combine with other tricyclic antidepressants due to additive toxicity risks 8
- Monitor carefully in patients with cardiovascular disease, as 5 of 7 patients who developed cardiac side effects in one study had prior organic heart disease 6