What is the incidence of constipation in patients taking nortriptyline (tricyclic antidepressant)?

Constipation Incidence with Nortriptyline

Constipation is a common side effect of nortriptyline, occurring in approximately 50% of patients taking tricyclic antidepressants (TCAs) including nortriptyline. 1

Incidence and Risk Factors

• Nortriptyline, like other TCAs, causes constipation through its anticholinergic effects, which reduce gastrointestinal motility 1
• Constipation is specifically listed as one of the most common side effects of nortriptyline in clinical practice guidelines 1
• Higher plasma concentrations of nortriptyline (80-120 ng/ml) are associated with significantly more frequent constipation compared to lower concentrations (40-60 ng/ml) 2
• Risk factors that may worsen nortriptyline-induced constipation include:
  • Limited fluid intake 3
  • Poor dietary habits 3
  • Sedentary lifestyle 3
  • Advanced age (elderly patients are more sensitive to anticholinergic effects) 4
  • Poor CYP2D6 metabolizer status (genetic variation can lead to higher drug levels and increased side effects) 5

Comparative Incidence

• Among antidepressants, TCAs like nortriptyline have a higher incidence of constipation compared to SSRIs 1
• While all TCAs cause constipation, secondary amines like nortriptyline may have fewer anticholinergic side effects than tertiary amines like amitriptyline 1
• In a meta-analysis of gastrointestinal side effects, mirtazapine was shown to have fewer side effects on the gut compared to other antidepressants, while escitalopram and sertraline had more gastrointestinal side effects (though different in nature - more diarrhea than constipation) 6

Management Considerations

• Constipation with nortriptyline should be anticipated and treated prophylactically with a stimulating laxative to increase bowel motility 1
• For patients at high risk of constipation, consider:
  • Starting at lower doses (10-25mg) and titrating slowly 4
  • Increasing fluid intake and physical activity when appropriate 1
  • Adding bisacodyl 10-15 mg, 2-3 times daily if constipation develops 1
• In patients with gastroparesis, nortriptyline should be used with caution as it may worsen symptoms 7

Clinical Implications

• Constipation is one of the most common reasons for poor medication adherence with TCAs 6
• While constipation is common with nortriptyline, it rarely leads to severe complications compared to some antipsychotics (particularly clozapine) 3
• For patients who cannot tolerate the constipating effects of nortriptyline, consider alternative antidepressants with lower rates of constipation, such as SSRIs 1