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

Nortriptyline Side Effects

Nortriptyline commonly causes anticholinergic side effects including dry mouth, constipation, blurred vision, somnolence, and weight gain, along with cardiac effects such as prolonged QTc interval and orthostatic hypotension, though it has fewer anticholinergic effects than amitriptyline. 1

Common Anticholinergic Side Effects

• Dry mouth is one of the most frequently reported side effects, occurring significantly more often in women throughout treatment 2
• Constipation occurs commonly due to anticholinergic activity on the gastrointestinal tract 1
• Blurred vision results from anticholinergic effects on pupillary accommodation 1
• Urinary retention or difficulty urinating can occur, particularly in elderly patients or those with prostatic hypertrophy 3
• Somnolence is a prominent effect, making nortriptyline useful for patients with agitated depression and insomnia 1

Cardiovascular Side Effects

• Prolonged QTc interval on ECG is a significant concern requiring baseline ECG monitoring 1
• Orthostatic hypotension occurs but is relatively less common with nortriptyline compared to other tricyclics 4
• Increased heart rate occurs during treatment, with men experiencing greater increases in supine heart rate (particularly during weeks 4-6) than women, despite similar plasma drug levels 2
• Cardiac arrhythmias are possible, especially in patients with preexisting cardiac disease 3

Metabolic and Weight Effects

• Weight gain is a common side effect that may worsen obstructive sleep apnea in susceptible patients 1
• Blood sugar fluctuations (both elevation and lowering) have been reported, with significant hypoglycemia documented when combined with chlorpropamide in diabetic patients 3

Neuropsychiatric Side Effects

• Suicidal ideation and behavior, particularly in children, adolescents, and young adults during early treatment or dose adjustments 3
• Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania may emerge, especially early in treatment 3
• Exacerbation of psychosis in schizophrenic patients or activation of latent schizophrenic symptoms 3
• Epileptiform seizures may accompany administration 3
• Cognitive dysfunction can occur, particularly in elderly patients at higher doses 3

Time Course and Plasma Level Correlation

• Side effects diminish significantly over time, with most subjective complaints absent by the fourth week of treatment 5
• Higher plasma levels correlate with increased side effects, though therapeutic levels (50-150 ng/mL) should be maintained 1, 5
• Many somatic complaints initially attributed to nortriptyline are actually depression symptoms, as evidenced by a 50% decline in somatic complaints during acute treatment 6

Sex-Related Differences

• Women experience more persistent dry mouth throughout the entire 6-week treatment period 2
• Men show greater susceptibility to heart rate increases, particularly in supine position during weeks 4-6 of treatment 2

Drug Interactions Increasing Side Effects

• Cimetidine significantly elevates tricyclic serum levels, causing severe anticholinergic symptoms (severe dry mouth, urinary retention, blurred vision) 3
• Fluoxetine can cause greater than 2-fold increases in previously stable nortriptyline plasma levels due to its long half-life (4-16 days for norfluoxetine) 3
• Alcohol response may be exaggerated during nortriptyline treatment 3

Clinical Monitoring Recommendations

• Baseline ECG is essential before initiating treatment to assess QTc interval 1
• Therapeutic drug monitoring with target levels of 50-150 ng/mL helps optimize efficacy while minimizing toxicity 1
• Close monitoring for emergence of suicidal ideation is critical, especially during the first few weeks and after dose adjustments 3
• Elderly patients require lower starting doses (10 mg at bedtime) due to increased sensitivity to side effects 1, 4

Comparative Tolerability

• Nortriptyline has fewer anticholinergic and antihistaminergic effects than amitriptyline, making it preferable for elderly patients 1, 4
• Overall dropout rates due to adverse effects range from 4-12% in clinical trials, with no serious adverse events reported in smoking cessation studies 7
• Nortriptyline is generally well-tolerated in elderly patients when dosed appropriately, with a favorable side effect profile compared to tertiary amine tricyclics 4