Clinical Side Effects of Nortriptyline
Nortriptyline commonly causes anticholinergic side effects including dry mouth, constipation, blurred vision, and sedation, as well as cardiovascular effects such as increased heart rate and potential QTc prolongation. 1, 2
Common Side Effects
Anticholinergic Effects
- Dry mouth - one of the most consistently reported side effects, persisting throughout treatment 1, 3
- Constipation - common but may be less severe than with other tricyclic antidepressants 1
- Blurred vision - due to anticholinergic properties 1
- Urinary retention - related to anticholinergic activity 2
Cardiovascular Effects
- Increased heart rate - consistently higher in nortriptyline-treated patients compared to placebo 3
- QTc prolongation - requires ECG monitoring, especially in patients with pre-existing cardiac conditions 1
- Orthostatic hypotension - may cause dizziness when standing 2
Neurological Effects
- Sedation/somnolence - particularly common when initiating therapy 1
- Cognitive dysfunction - may include confusion and disturbed concentration 2
- Dizziness - often dose-related 2
Other Effects
- Weight gain - less prominent than with some other tricyclics 1
- Sexual dysfunction - including decreased libido or erectile dysfunction 2
Sex-Related Differences in Side Effects
Research has identified some important sex-related differences in nortriptyline side effects:
- Men experience greater increases in heart rate during weeks 4-6 of treatment despite similar plasma drug levels 4
- Women report more persistent dry mouth throughout treatment 4
Monitoring and Management
Initial Assessment
- Baseline ECG recommended before starting treatment, particularly in patients over 65 or with cardiovascular risk factors 5
- Start with low doses (10-25 mg at bedtime) and gradually titrate to minimize side effects 1, 5
Ongoing Monitoring
- Regular assessment of anticholinergic side effects
- Cardiovascular monitoring, particularly heart rate and blood pressure
- Watch for signs of toxicity including confusion, visual hallucinations, agitation, or severe drowsiness 2
Important Clinical Considerations
Distinguishing Side Effects from Symptoms
- Many somatic complaints attributed to nortriptyline may actually be symptoms of the underlying condition being treated
- Studies show up to 50% reduction in somatic complaints during treatment, suggesting these were symptoms of depression rather than medication side effects 6
Overdose Risk
- Overdose can be fatal and requires immediate hospitalization
- Critical manifestations include cardiac dysrhythmias, severe hypotension, seizures, and CNS depression 2
- QRS widening on ECG is a significant indicator of toxicity 2
Advantages of Nortriptyline vs. Other TCAs
- Nortriptyline generally has a superior side effect profile compared to amitriptyline 1
- Once-daily dosing is possible and may improve adherence without increasing side effects 7
Special Populations
Elderly Patients
- More susceptible to anticholinergic effects and orthostatic hypotension
- Long-term studies show that dry mouth and increased heart rate persist during maintenance therapy, while other side effects may diminish 3
- Use with caution in patients over 65 due to anticholinergic effects 5
Patients with Neuropathic Pain
- Nortriptyline is often preferred over other TCAs for neuropathic pain due to its better tolerability 1
- Typical dosing for neuropathic pain is 25-100 mg at bedtime 1
By understanding these side effects and implementing appropriate monitoring, clinicians can optimize the risk-benefit profile of nortriptyline therapy for their patients.