Nortriptyline is More Likely to Cause Constipation Than Pristiq
Nortriptyline (a tricyclic antidepressant) carries a significantly higher risk of constipation compared to Pristiq (desvenlafaxine, an SNRI), primarily due to its potent anticholinergic effects that directly slow gastrointestinal motility.
Mechanism and Comparative Risk
Tricyclic Antidepressants (Nortriptyline)
Nortriptyline causes constipation through anticholinergic mechanisms, which is listed as one of the common side effects alongside sedation, dry eyes, and dry mouth 1.
Constipation occurs dose-dependently with nortriptyline: In a 3-year maintenance study, constipation occurred significantly more frequently at higher plasma levels (80-120 ng/ml) compared to lower levels (40-60 ng/ml) 2.
Tricyclic antidepressants cause constipation more frequently than other antidepressant classes due to their anticholinergic properties 3.
Nortriptyline is a secondary amine TCA, which may have fewer anticholinergic side effects than tertiary amines like amitriptyline, but constipation remains a prominent adverse effect 1.
SNRIs (Pristiq/Desvenlafaxine)
Desvenlafaxine lists constipation OR diarrhea as possible side effects, indicating bidirectional gastrointestinal effects rather than a predominant constipating effect 1.
The most common adverse effects of desvenlafaxine are insomnia, somnolence, dizziness, and nausea—not constipation 4.
Desvenlafaxine actually inhibits gastric motility through sympathetic activation rather than anticholinergic mechanisms, which may paradoxically cause varied GI symptoms 5.
Clinical Implications
When Constipation is a Concern
Choose Pristiq over nortriptyline if constipation risk is problematic, particularly in elderly patients, those with baseline constipation, or patients taking other constipating medications.
If nortriptyline must be used despite constipation risk, start with lower doses (10 mg at night) and titrate slowly 1.
Managing Constipation if Nortriptyline is Required
Use polyethylene glycol (PEG) as first-line therapy for TCA-induced constipation 3.
Add stimulant laxatives (bisacodyl or senna) for persistent constipation 3.
Promote adequate fluid intake and physical activity 3.
Important Caveat
While nortriptyline has higher constipation risk, both medications can cause gastrointestinal side effects through different mechanisms: nortriptyline through anticholinergic blockade and desvenlafaxine through sympathetic activation 1, 5.
The constipation risk with nortriptyline is consistent and predictable, whereas desvenlafaxine may cause either constipation or diarrhea in different patients 1.