Sweating is NOT an Anticholinergic Side Effect
Sweating is the correct answer—it is NOT an anticholinergic side effect of tricyclic antidepressants. In fact, sweating represents a cholinergic or sympathomimetic effect, which is the opposite of anticholinergic activity.
Understanding Anticholinergic Effects of TCAs
Tricyclic antidepressants block muscarinic acetylcholine receptors, leading to predictable anticholinergic side effects 1:
- Dry mouth (not increased salivation) 1
- Urinary retention (not increased urination) 1, 2
- Blurred vision (due to impaired accommodation) 2
- Constipation (not diarrhea) 1, 2
- Orthostatic hypotension 1
Why Sweating is Different
Sweating (diaphoresis) is actually associated with increased cholinergic activity or serotonergic effects, not anticholinergic blockade 3. The American Gastroenterological Association specifically notes that the presence of diaphoresis argues against pure anticholinergic toxicity 3.
When patients experience sweating on antidepressants, this typically represents:
- Serotonergic effects (as seen with SSRIs and SNRIs like duloxetine) 4
- Sympathetic activation
- A sign of potential serotonin syndrome when combined with other serotonergic agents 3
Clinical Management of True Anticholinergic Effects
The anticholinergic burden of TCAs can be reduced by 1:
- Starting with low doses (10 mg/day in older patients) and titrating slowly 1
- Using secondary amine TCAs (nortriptyline or desipramine) which have less anticholinergic activity than tertiary amines like amitriptyline 1
- Administering at bedtime to minimize daytime anticholinergic symptoms 1
Important Caveat
Caution should be exercised in patients with glaucoma, benign prostatic hypertrophy, or cardiovascular disease due to the anticholinergic effects of urinary retention, blurred vision, and cardiac conduction abnormalities 5, 2.