What are the side effects of nortriptyline in an adult patient with a history of depression?

Side Effects of Nortriptyline in Adults with Depression

Nortriptyline is generally well-tolerated in adults with depression, but you should counsel patients about anticholinergic effects (dry mouth, constipation, urinary hesitancy), cardiovascular effects (tachycardia, orthostatic hypotension), and sedation as the most common side effects. 1, 2

Common Side Effects

Anticholinergic Effects

• Dry mouth, constipation, and urinary hesitancy are the most frequent anticholinergic complaints, though nortriptyline has lower anticholinergic activity compared to tertiary amine tricyclics like amitriptyline 1
• Constipation occurs significantly more often at higher therapeutic plasma levels (80-120 ng/ml versus 40-60 ng/ml) 3
• Blurred vision and urinary retention can occur, particularly when combined with other anticholinergic medications 2

Cardiovascular Effects

• Nortriptyline causes sinus tachycardia with heart rate increases of 14.5-18 beats per minute 4
• Orthostatic hypotension occurs but is relatively less common than with other tricyclics 1, 5
• The drug prolongs cardiac conduction time and may affect rate-corrected repolarization 4
• Myocardial infarction, arrhythmias, and strokes have been reported, requiring close supervision in patients with cardiovascular disease 2

Central Nervous System Effects

• Sedation is a prominent effect, making nortriptyline useful for patients with agitated depression and insomnia 1
• The drug lowers the seizure threshold and should be used cautiously in patients with seizure history 2
• Nortriptyline may impair mental and physical abilities required for operating machinery or driving 2

Serious Adverse Effects Requiring Monitoring

Suicidality Risk

• In adults aged 18-24 years, there is an increased risk of suicidal behavior (5 additional cases per 1000 patients treated compared to placebo) 2
• The risk is highest during the first month of treatment and at times of dose changes 2
• Adults over 65 years show a protective effect against suicidal behavior (6 fewer cases per 1000 patients) 2

Psychiatric Symptoms

• Monitor for anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania 2
• In schizophrenic patients, nortriptyline may exacerbate psychosis or activate latent symptoms 2
• The drug may precipitate manic episodes in bipolar patients 2

Metabolic Effects

• Both elevation and lowering of blood sugar levels have been reported 2
• Significant hypoglycemia can occur when added to oral hypoglycemic agents in diabetic patients 2

Temporal Pattern of Side Effects

Many somatic complaints attributed to nortriptyline side effects are actually symptoms of depression that improve with treatment. Research shows that somatic complaints decline by 50% during acute treatment, indicating that initial complaints may reflect the underlying depression rather than medication side effects 6

Drug Interactions Causing Side Effects

• Cimetidine significantly increases nortriptyline levels, causing severe anticholinergic symptoms (severe dry mouth, urinary retention, blurred vision) 2
• Fluoxetine can cause greater than 2-fold increases in nortriptyline plasma levels 2
• Alcohol consumption has a potentiating effect and increases risk of suicidal attempts or overdosage 2

Clinical Pitfalls to Avoid

• Do not use nortriptyline in patients with brain metastases or elevated seizure risk 1
• Screen all patients for bipolar disorder before initiating treatment, as antidepressant monotherapy may precipitate manic episodes 2
• Avoid in patients with glaucoma or urinary retention history due to anticholinergic activity 2
• Exercise extreme caution in hyperthyroid patients or those on thyroid medication due to arrhythmia risk 2
• Most therapeutic benefits and side effects do not manifest until the fourth week of treatment 7

Comparative Safety Profile

Nortriptyline has a more favorable side effect profile than tertiary amine tricyclics (amitriptyline, imipramine), with lower anticholinergic activity and relatively fewer cardiac side effects 1, 5. It is recommended as the tricyclic-of-first-choice in elderly patients with major depression 5.