Drug treatment for IBS has been fraught with problems of efficacy and wrought with issues of excessive expense. Amitriptyline, an old serotonin simulator, is cheap, helps one sleep, and recently found sort of efficacious.
Ford, Alexander C., et al.
Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial.
The Lancet 402.10414 (2023): 1773-1785.
https://www.thelancet.com/article/S0140-6736(23)01523-4/abstract
- started with 10 mg and worked up to max of 30 mg
- mild anticholinergic side effects (dry mouth, slower urination, constipation)
- 3/4 stayed in study
- “Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS [symptoms severity scale] score between groups at 6 months (–27·0, 95% CI –46·9 to –7·10; p=0·0079).”
- Pain-wise not so great:
≥30% decrease in abdominal pain severity:
52% of amitriptyline vs 47% placebo at 3 months
It might have beneficial effects on dementia prevention:
Appleby, Brian S., et al.
A review: treatment of Alzheimer’s disease discovered in repurposed agents.
Dementia and geriatric cognitive disorders 35.1-2 (2013): 1-22.
https://karger.com/Article/FullText/345791
“Amitriptyline, a tricyclic antidepressant, is used to treat depression, migraine, and neuropathic pain. Patients taking amitriptyline have an increased serum concentration of brain-derived neurotrophic growth factor, and AD animal models have shown that it increases hippocampal brain-derived neurotrophic growth factor and dentate gyrus neurogenesis (table 4) [107,108]. Cellular models show that amitriptyline binds to the neurotrophin receptors, TrkA and TrkB, which may prevent apoptosis and promote neurite outgrowth [109]. Although it may increase total Aβ in animal models, this is due to an increase in the nontoxic Aβ monomer while decreasing the toxic Aβ dimer [110]. Alternatively, some non-AD animal models have suggested that amitriptyline may have a proapoptotic effect [110]. Nortriptyline may stop the formation of mitochondrial permeability transition pores and release of cytochrome c preventing apoptosis (table 2) [110].”
Helps neurogenesis in aged mice:
Chadwick, Wayne, et al.
Amitriptyline-mediated cognitive enhancement in aged 3× Tg Alzheimer’s disease mice is associated with neurogenesis and neurotrophic activity.
PloS one 6.6 (2011): e21660.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0021660
Comment – might help with sleep as constipation not greater than placebo but watch daytime drowsiness. Suggest probiotics too (Align etc)