What are the side effects of Nortriptyline (tricyclic antidepressant)?

Nortriptyline Side Effects

Nortriptyline causes anticholinergic side effects (dry mouth, constipation, blurred vision), cardiovascular effects (increased heart rate, orthostatic hypotension, QTc prolongation), and sedation, though it has fewer anticholinergic effects than amitriptyline, making it the preferred tricyclic antidepressant for elderly patients. 1, 2

Anticholinergic Side Effects

• Dry mouth is the most consistently reported anticholinergic effect, occurring more frequently with nortriptyline than placebo and persisting throughout long-term treatment 2, 3
• Constipation occurs due to anticholinergic activity on the gastrointestinal tract, though long-term studies show no significant increase compared to placebo 2, 3
• Blurred vision results from anticholinergic effects on pupillary accommodation 2
• Urinary retention can occur, particularly in elderly patients or those with prostatic hypertrophy 4
• These anticholinergic effects can be minimized by starting with low doses (10 mg/day in elderly patients) and titrating slowly to 75 mg/day 1

Cardiovascular Side Effects

• Increased heart rate is a consistent finding, with men showing greater increases than women during weeks 4-6 of treatment 3, 5
• Orthostatic hypotension occurs commonly and requires monitoring, especially during dose initiation 1, 2
• QTc prolongation is a critical concern requiring baseline ECG monitoring; if PR or QTc interval is prolonged, nortriptyline should not be used 1, 2
• Doses exceeding 100 mg/day are associated with increased risk of sudden cardiac death, necessitating extreme caution in patients with cardiovascular disease 1, 2
• Baseline ECG is essential before initiating treatment to assess cardiac conduction 1, 2

Central Nervous System Effects

• Somnolence is prominent, making nortriptyline useful for patients with insomnia, though this effect is often related to residual depression rather than the medication itself 2, 3
• Confusion, disturbed concentration, and transient visual hallucinations can occur, particularly in overdose situations 4
• Seizures may occur in overdose and should be controlled with benzodiazepines 4

Metabolic Effects

• Weight gain is common and may worsen obstructive sleep apnea in susceptible patients 2
• Weight changes during long-term treatment show no significant difference compared to placebo in some studies 3

Overdose Manifestations

• Critical manifestations include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma 4
• QRS duration ≥0.10 seconds on ECG is the best indicator of overdose severity 4
• Deaths may occur from overdosage, requiring immediate hospital monitoring and gastric decontamination 4
• Intravenous sodium bicarbonate should be used to maintain serum pH between 7.45-7.55 in overdose 4

Clinical Monitoring Requirements

• Therapeutic drug monitoring with target levels of 50-150 ng/mL helps optimize efficacy while minimizing toxicity 2
• Plasma levels vary widely between individuals receiving the same dose, and higher plasma levels correlate significantly with increased side effects 6
• Side effects typically diminish significantly over time, with most absent by the fourth week of treatment 7, 6
• Many somatic complaints initially attributed to nortriptyline are actually symptoms of depression, as evidenced by a 50% decline in somatic complaints during acute treatment 7

Comparative Tolerability Advantages

• Nortriptyline has fewer anticholinergic and antihistaminergic effects than amitriptyline, making it the preferred tricyclic for elderly patients 1, 2
• As a secondary amine TCA, nortriptyline causes less cholinergic blockade compared to tertiary amines like amitriptyline and imipramine 1

Key Clinical Pitfalls to Avoid

• Do not use nortriptyline in patients with prolonged QTc interval or recent myocardial infarction 2
• Avoid doses exceeding 100 mg/day due to sudden cardiac death risk 1, 2
• Do not attribute all somatic complaints to medication side effects, as many represent residual depressive symptoms 7
• In overdose, do not use Type 1A and 1C antiarrhythmics (quinidine, disopyramide, procainamide) as they are generally contraindicated 4