While, drowsiness, headache, dry mouth, nausea are very commonly reported side effects seen with a frequency of more than 10 percent, both diarrhoea and constipation have been reported commonly. Other commonly reported adverse effects which might significantly impact the quality of life in advanced cancer include sleep disturbances and sexual dysfunction.

While efficacy is considered comparable to amitriptyline, as per the results of a single RCT, duloxetine was associated with a higher incidence of constipation and lower incidence of dry mouth.

Rare side effects include hypertensive crises and Stevens-Johnson syndrome.

It is also known to be associated with bleeding (like SSRI’s and venlafaxine), lowering seizure threshold and carries a risk of hypertension and arrythmia (cautious use in cardiac disease).

Reference

Wilcock, A., Howard, P., Toller, C. S., Droney, J., & Charlesworth, S. (Eds.). (2025). Palliative care formulary (9th ed.). Pharmaceutical Press.