Amitriptyline
Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026
Prescription tricyclic antidepressant (TCA) originally approved for major depressive disorder but now more commonly used for chronic neuropathic pain, migraine prophylaxis, and fibromyalgia due to its analgesic properties. Carries significant anticholinergic and cardiac risks at higher doses. Lethal in overdose, which limits its use as a first-line antidepressant. Dosage must be determined by your prescribing physician.
Exploratory record, not a reviewed medical publication.
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This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.
What the research says.
A quick, data-only summary. The full evidence, dosing, and sources are below.
Prescription tricyclic antidepressant (TCA) originally approved for major depressive disorder but now more commonly used for chronic neuropathic pain, migraine prophylaxis, and fibromyalgia due to its analgesic properties. NutriStack rates the supporting evidence as strong. Common adult dosing is 10–75 mg at bedtime for pain; 50–300 mg daily for depression (as prescribed by your physician), though a prescriber sets the actual dose. With long-term use it can deplete sodium. This profile indexes 10 sources.
The bottom line
Evidence rating strong. Most-documented uses: neuropathic pain relief, migraine prophylaxis, depression symptom relief. 10 sources indexed (2008–2025), with 0 interaction records on file.
How it works, mechanistically.
Core mechanism
Inhibits the reuptake of serotonin and norepinephrine by blocking SERT and NET. Also antagonizes histamine H1 receptors (sedation), muscarinic acetylcholine receptors (anticholinergic effects), and alpha-1 adrenergic receptors (orthostatic hypotension). Blocks sodium channels at cardiac tissue, contributing to cardiotoxicity in overdose.
Dosing & protocol.
Can be taken with or without food. Typically administered at bedtime due to sedating effects. Highly lipophilic with large volume of distribution.7
What it depletes.
Nutrients this medication can lower over time, and what to replace.
Sodium
ModerateAntidepressant-associated SIADH can increase renal free-water retention and dilute serum sodium, producing hyponatremia.
Full safety detail.
Side effects
- Sedation and drowsiness
- Dry mouth
- Constipation
- Urinary retention
- Weight gain
- Orthostatic hypotension
- Blurred vision
- QT prolongation and cardiac arrhythmias
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Meta-analyses & systematic reviews
5- 1Amitriptyline's anticholinergic adverse drug reactions-A systematic multiple-indication review and meta-analysisPMIDBrueckle MS, Thomas ET, Seide SE et al. · PloS one · 2023
Brueckle MS, Thomas ET, Seide SE et al.. Amitriptyline's anticholinergic adverse drug reactions-A systematic multiple-indication review and meta-analysis. PloS one. 2023
- 2Comparison of Amitriptyline and US Food and Drug Administration-Approved Treatments for Fibromyalgia: A Systematic Review and Network Meta-analysis.PMIDFarag HM, Yunusa I, Goswami H et al. · JAMA Network Open · 2022
Network meta-analysis found amitriptyline was among the most effective treatments for fibromyalgia, showing significant pain reduction and sleep improvement comparable to FDA-approved treatments (duloxetine, milnacipran, pregabalin).
- 3Amitriptyline and Sexual Function: A Systematic Review Updated for Sexual Health PracticePMIDChen LW, Chen MY, Lian ZP et al. · American journal of men's health · 2018
Chen LW, Chen MY, Lian ZP et al.. Amitriptyline and Sexual Function: A Systematic Review Updated for Sexual Health Practice. American journal of men's health. 2018
- 4Amitriptyline for musculoskeletal complaints: a systematic reviewPMIDvan den Driest JJ, Bierma-Zeinstra SMA, Bindels PJE et al. · Family practice · 2017
van den Driest JJ, Bierma-Zeinstra SMA, Bindels PJE et al.. Amitriptyline for musculoskeletal complaints: a systematic review. Family practice. 2017
- 5Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacyPMIDNishishinya B, Urrútia G, Walitt B et al. · Rheumatology (Oxford, England) · 2008
Nishishinya B, Urrútia G, Walitt B et al.. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford, England). 2008
Randomized controlled trials
2- 6Comparison of Duloxetine Supplemented With Pregabalin and Amitriptyline Supplemented With Pregabalin for the Treatment of Postherpetic Neuralgia: A Double-Blind, Randomized Crossover TrialPMIDWang Y, Wu C, Liu Y et al. · CNS neuroscience & therapeutics · 2025
Wang Y, Wu C, Liu Y et al.. Comparison of Duloxetine Supplemented With Pregabalin and Amitriptyline Supplemented With Pregabalin for the Treatment of Postherpetic Neuralgia: A Double-Blind, Randomized Crossover Trial. CNS neuroscience & therapeutics. 2025
- 7Amitriptyline 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 trialPMIDFord AC, Wright-Hughes A, Alderson SL et al. · Lancet (London, England) · 2023
Ford AC, Wright-Hughes A, Alderson SL 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. Lancet (London, England). 2023
Reference material
3- 8Moore RA et al. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015.Source linkedPMID
- 9Cipriani A et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018.Source linkedPMID
- 10Abouelmagd ME et al. Efficacy and Safety of Melatonin in Migraine Prophylaxis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr Pain Headache Rep. 2026.Source linkedPMID
Common questions.
Quick answers about Amitriptyline, drawn from the data on this page.
What is Amitriptyline?
Prescription tricyclic antidepressant (TCA) originally approved for major depressive disorder but now more commonly used for chronic neuropathic pain, migraine prophylaxis, and fibromyalgia due to its analgesic properties. Carries significant anticholinergic and cardiac risks at higher doses. Lethal in overdose, which limits its use as a first-line antidepressant. Dosage must be determined by your prescribing physician.
What is Amitriptyline used for?
Commonly cited benefits of Amitriptyline include: Neuropathic pain relief; Migraine prophylaxis; Depression symptom relief; Fibromyalgia pain improvement; Sleep improvement. NutriStack rates the overall evidence as strong.
What is a typical dose of Amitriptyline?
A typical adult dose of Amitriptyline is 10–75 mg at bedtime for pain; 50–300 mg daily for depression (as prescribed by your physician). The commonly recommended form is Tablet. These are general ranges, not personalized advice; confirm the right dose with a clinician.
What are the side effects of Amitriptyline?
Reported side effects include sedation and drowsiness, dry mouth, constipation, urinary retention, weight gain, orthostatic hypotension. This is educational information; check with a healthcare professional before use.
How strong is the evidence for Amitriptyline?
NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.
Use this with your stack
Amitriptyline in NutriStack.
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