medicationPrescription only (US)Amitriptyline is an FDA-approved tricyclic antidepressant, first approved decades ago and still prescribed off-label for chronic pain conditions such as fibromyalgia, as discussed in the cited review
AmitriptylineBenefits, Dosage & Interactions
Also known as: Elavil
Amitriptyline, commonly known by its former brand name Elavil, is a tricyclic antidepressant (TCA) medication. It was one of the first antidepressants developed and has been in use for several decades. It is typically taken in the evening. The reported plasma half-life is about 10 hours, which shapes dosing frequency.
How much Amitriptyline do people take?
Historically dosed at 75–150 mg/day for depression, and at much lower doses (10–50 mg/day) in the fibromyalgia and neuropathic-pain literature reviewed here. Route reported: Oral tablet, as used in the cited pharmacology review and fibromyalgia literature review. Frequency reported: Typically once daily, most often at night because of sedation. These are amounts documented in the cited studies and labels for Amitriptyline — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.
See the full reported protocol and its sourcesResearched by DoseRoutine Research TeamReviewed for accuracy by Nicholas Alexander, RSE, SO, PMPLast updated Educational reference only — not medical advice. Always confirm dosing and safety decisions with a licensed clinician.
Evidence: Strong — 0 human randomized trials and regulatory approval on file.
Evidence strengthStrong · 4/4
PreclinicalStrong human evidence
0 human randomized trials and regulatory approval on file.
Plasma half-life
10–28 h
Typical timing
in the evening
Default unit
mg
What published protocols report
Ranges documented in the literature, shown for reference. DoseRoutine does not recommend an amount — your prescriber or the product label sets the dose.
- Reported amounts
- Historically dosed at 75–150 mg/day for depression, and at much lower doses (10–50 mg/day) in the fibromyalgia and neuropathic-pain literature reviewed here[1][2]
- Route studied
- Oral tablet, as used in the cited pharmacology review and fibromyalgia literature review[1][2]
Reported for Amitriptyline in the cited sources. Published ranges are not dosing advice.
References & evidence
Documents the Amitriptyline entry is written from. Each number matches an inline marker above.
- [1]Classics in Chemical Neuroscience: AmitriptylineMcClure EW, Daniels RN · ACS Chemical Neuroscience · 2021 · Peer-reviewed · PMID 33438398
- [2]Amitriptyline for the treatment of fibromyalgia: a comprehensive reviewRico-Villademoros F, Slim M, Calandre EP · Expert Review of Neurotherapeutics · 2015 · Peer-reviewed · PMID 26395929
References & Evidence
Sources on this page that document Amitriptyline dosing, timing and safety.
- [1]U.S. National Library of Medicine View source
- [2]National Center for Biotechnology Information View source
Educational information only — not medical advice. Dose ranges vary by person, indication and prescriber.
What is Amitriptyline?Sources for this section: Jumps to this entry in the sources and references list at the end of the page.
Amitriptyline, commonly known by its former brand name Elavil, is a tricyclic antidepressant (TCA) medication. It was one of the first antidepressants developed and has been in use for several decades. While initially primarily prescribed for depression, its applications have expanded over time due to its diverse pharmacological properties. Today, it is also frequently used to manage various types of neuropathic pain, prevent migraines, and treat certain sleep disorders or functional bowel conditions. As a medication, its use requires careful consideration and professional medical guidance due to potential side effects and interactions. (DrugBank, Mayo Clinic)
What does the research say about Amitriptyline?
Tap a section to expand.
Amitriptyline exerts its therapeutic effects primarily by influencing neurotransmitter levels in the brain. It is a potent inhibitor of the reuptake of both serotonin and norepinephrine into presynaptic neurons. By blocking the reabsorption of these neurotransmitters, amitriptyline increases their concentrations in the synaptic cleft, thereby enhancing their availability to bind to postsynaptic receptors. This action is believed to be the main mechanism behind its antidepressant effects.
In addition to its reuptake inhibition properties, amitriptyline also possesses significant antagonistic activity at several other receptor types. It blocks muscarinic cholinergic receptors, which contributes to common anticholinergic side effects such as dry mouth, constipation, and blurred vision. It also acts as an antagonist at histamine H1 receptors, which is thought to contribute to its sedative properties. Furthermore, amitriptyline has alpha-1 adrenergic blocking effects, which can lead to orthostatic hypotension. Its complex pharmacological profile, impacting multiple neurotransmitter systems, explains its broad range of therapeutic uses and potential side effects. (DrugBank, PubChem)
Source for this section: Sources for How does Amitriptyline work?: Jumps to this entry in the sources and references list at the end of the page.
Amitriptyline has been studied and used for several medical conditions:
* **Depression:** As a tricyclic antidepressant, it is effective in treating major depressive disorder, particularly in cases where newer antidepressants may not be suitable or effective. (Cochrane, Mayo Clinic)
* **Neuropathic Pain:** It is widely recognized for its efficacy in managing various chronic neuropathic pain conditions, including postherpetic neuralgia, diabetic neuropathy, and other nerve-related pains. Its pain-relieving effects are thought to be separate from its antidepressant actions. (NIH, Cochrane)
* **Migraine Prevention:** Amitriptyline is often prescribed as a prophylactic treatment to reduce the frequency and severity of migraine headaches in adults. (Mayo Clinic)
* **Tension-Type Headache Prevention:** Similar to migraines, it can be used to prevent chronic tension-type headaches. (Mayo Clinic)
* **Chronic Pelvic Pain:** It may be used to help manage chronic pelvic pain conditions. (Mayo Clinic)
* **Irritable Bowel Syndrome (IBS):** In lower doses, it can be beneficial for some individuals with IBS, particularly those with diarrhea-predominant symptoms, due to its anticholinergic and neuromodulatory effects. (NIH)
* **Insomnia:** Its sedative properties can be utilized, in some cases, to aid sleep, though this is often an Off-label use. (MedlinePlus)
Research on amitriptyline has been conducted for decades, establishing its efficacy in several areas. For major depressive disorder, numerous randomized controlled trials (RCTs) and meta-analyses have affirmed its antidepressant effects, although it is often reserved for specific cases due to its side effect profile compared to newer agents. (Cochrane)
In the realm of pain management, systematic reviews and meta-analyses, including those by Cochrane, consistently support amitriptyline's effectiveness in reducing pain intensity for various neuropathic conditions, such as diabetic neuropathy and postherpetic neuralgia. Its efficacy for migraine prevention is also well-documented in clinical guidelines and studies. (NIH, Mayo Clinic)
Studies for off-label uses like IBS or insomnia, while not always as robust as those for its primary indications, also suggest benefit based on observations and smaller trials. Due to its long history, much of the foundational evidence for amitriptyline predates modern double-blind, placebo-controlled trial standards, but its clinical utility remains widely recognized and supported by extensive clinical experience. (MedlinePlus, DrugBank)
Like all medications, amitriptyline can cause side effects. The likelihood and severity of these can vary between individuals. Common side effects often relate to its anticholinergic and sedative properties:
* **Very Common (Affecting more than 1 in 10 people):** Dry mouth, sedation/drowsiness, dizziness, headache, constipation, blurred vision, difficulty urinating, sweating, weight gain, orthostatic hypotension (fall in blood pressure upon standing). (FDA label)
* **Common (Affecting up to 1 in 10 people):** Nausea, vomiting, diarrhea, tremors, confusion (especially in older adults), increased heart rate, changes in appetite, sexual dysfunction, weakness, taste disturbance. (FDA label)
* **Less Common:** Arrhythmias, heart block, palpitations, nervousness, anxiety, restlessness, insomnia, nightmares, rash, hives, swelling of the face/tongue, tinnitus, disorientation, seizures, bone marrow suppression. (FDA label)
* **Serious (Requires immediate medical attention):** Severe allergic reaction (rash, itching/swelling, severe dizziness, trouble breathing), chest pain, fainting, irregular or rapid heartbeat, severe dizziness, mood changes (e.g., new or worsening depression, anxiety, agitation, panic attacks, hostility, impulsivity, irritability, aggression, violent behavior, suicidal thoughts), severe muscle stiffness, fever, confusion (neuroleptic malignant syndrome), yellowing eyes/skin (liver issues). (FDA label, MedlinePlus)
This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for What are the side effects of Amitriptyline?: Jumps to this entry in the sources and references list at the end of the page.
Amitriptyline carries several important warnings:
* **Suicidal Thoughts and Behaviors:** Like other antidepressants, amitriptyline can increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults (up to age 24) compared to placebo. Close monitoring is crucial, especially during initial therapy and dose changes. (FDA label)
* **Cardiovascular Effects:** Amitriptyline can cause arrhythmias, tachycardia, and changes in blood pressure. It should be used with caution in patients with pre-existing cardiovascular disease, including a history of myocardial infarction, stroke, or heart block. ECG monitoring may be recommended. (FDA label)
* **Central Nervous System (CNS) Depression:** Due to its sedative properties, amitriptyline can impair mental and physical abilities required for driving or operating machinery. Concurrent use with other CNS depressants (e.g., alcohol, sedatives, hypnotics) should be avoided or approached with extreme caution. (FDA label)
* **Anticholinergic Effects:** These can be pronounced, particularly in older adults, leading to urinary retention, severe constipation, blurred vision, and exacerbation of narrow-angle glaucoma. (FDA label)
* **Seizures:** Amitriptyline may lower the seizure threshold. Patients with a history of seizures should be monitored closely. (FDA label)
* **Activation of Mania/Hypomania:** In individuals with bipolar disorder, antidepressant treatment can precipitate a manic or hypomanic episode. Amitriptyline should be used with caution, and ideally, individuals should be screened for bipolar disorder before initiating treatment. (FDA label)
* **Serotonin Syndrome:** The risk of serotonin syndrome increases when amitriptyline is used concurrently with other serotonergic agents. (FDA label)
This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for Who should avoid Amitriptyline?: Jumps to this entry in the sources and references list at the end of the page.
Amitriptyline should not be used in certain situations:
* **Hypersensitivity:** Individuals with a known allergy to amitriptyline or any excipients in its formulation. (FDA label)
* **Concurrent Use with Monoamine Oxidase Inhibitors (MAOIs):** Amitriptyline must not be used concurrently with an MAOI or within 14 days of discontinuing an MAOI, due to the risk of severe, potentially fatal serotonin syndrome. Similarly, an MAOI should not be started within 14 days of discontinuing amitriptyline. (FDA label)
* **Acute Recovery Phase After Myocardial Infarction:** It is contraindicated in the acute recovery phase following a heart attack, typically within the first month. (FDA label)
* **Severe Liver Disease:** Due to its metabolism in the liver, severe hepatic impairment can lead to increased concentrations and toxicity. (FDA label)
* **Uncontrolled Narrow-Angle Glaucoma:** Its anticholinergic effects can worsen this condition. (FDA label)
* **Urinary Retention:** Can exacerbate existing urinary retention. (FDA label)
This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for When should Amitriptyline not be taken?: Jumps to this entry in the sources and references list at the end of the page.
Combining amitriptyline with certain other medications or substances can lead to dangerous interactions:
* **Monoamine Oxidase Inhibitors (MAOIs):** A absolute contraindication due to the high risk of serotonin syndrome, characterized by agitation, hallucinations, rapid heart rate, fever, muscle rigidity, and coma. (FDA label)
* **Other Serotonergic Drugs:** This includes Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), triptans for migraine, tramadol, linezolid, St. John's Wort, and fentanyl. Concurrent use increases the risk of serotonin syndrome. (FDA label)
* **CNS Depressants:** Alcohol, sedatives, hypnotics, opioids, and other medications that cause drowsiness can enhance the sedative effects of amitriptyline, increasing impairment and the risk of accidents. (FDA label)
* **Anticholinergic Drugs:** Medications such as atropine, antihistamines (e.g., diphenhydramine), or certain antipsychotics can additive anticholinergic effects (e.g., severe dry mouth, constipation, urinary retention, blurred vision, confusion). (FDA label)
* **Adrenergic Neuron Blocking Agents (e.g., Guanethidine, Clonidine):** Amitriptyline can significantly reduce the antihypertensive effect of these drugs. (FDA label)
* **QT Prolonging Drugs:** Combining with other drugs that prolong the QT interval (e.g., certain antiarrhythmics, antipsychotics, fluoroquinolone antibiotics) can increase the risk of serious cardiac arrhythmias. (FDA label)
* **Cimetidine:** May inhibit the metabolism of amitriptyline, leading to increased plasma concentrations and potential toxicity. (FDA label)
* **Thyroid Hormones:** Concomitant use may increase the risk of cardiac arrhythmias. (FDA label)
This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for What should you not mix with Amitriptyline?: Jumps to this entry in the sources and references list at the end of the page.
Amitriptyline has a relatively long half-life of approximately 20 hours, which means it stays in the body for an extended period. It is typically taken once daily, commonly at bedtime. This timing is often chosen to leverage its sedative properties, which can help with sleep and minimize daytime drowsiness side effects. It can be taken with or without food. However, consistency in timing helps maintain steady levels in the body. The full therapeutic effects for depression or pain conditions may take several weeks to become apparent. (FDA label, DrugBank)
Source for this section: Sources for When should you take Amitriptyline?: Jumps to this entry in the sources and references list at the end of the page.
Put it into practice
Reading about Amitriptyline is the first step — DoseRoutine helps you act on it. These free tools turn what you just learned into a routine.
What interacts with Amitriptyline?
Frequently asked questions about Amitriptyline
Amitriptyline is primarily used to treat depression, various forms of neuropathic pain (nerve pain), and to prevent migraine headaches. It's an older medication with a wide range of applications.
Amitriptyline frequently causes drowsiness and sedation as a side effect. Taking it at bedtime helps to mitigate daytime sleepiness and can also assist individuals who have difficulty sleeping.
While some effects like sedation might be noticed sooner, the full therapeutic benefits for conditions like depression or chronic pain typically take several weeks (e.g., 2 to 4 weeks or even longer) of consistent use to become apparent. It's important to continue taking it as prescribed.
Yes, weight gain is a recognized and common side effect of amitriptyline. This can be due to increased appetite. If this becomes a concern, discuss it with your healthcare provider.
No, amitriptyline is not considered addictive in the same way as opioids or benzodiazepines. However, stopping it abruptly, especially after long-term use, can lead to withdrawal-like symptoms such as nausea, headache, and malaise. It's important to gradually reduce the dose under medical supervision.
Interaction risk for Amitriptyline comes from the rest of the stack: other medications, prescription medicines, hormone therapy and peptides. Because Amitriptyline is usually taken in the evening, most avoidable conflicts come from what else lands in that same window. With a reported plasma half-life near 10 hours, separating doses can change the picture as much as removing one. Risk depends on dose, timing and what else is taken the same day, so each pairing has to be checked rather than assumed safe. The free checker at https://doseroutine.com/interaction-checker covers Amitriptyline with no sign-up.
Amitriptyline is typically taken in the evening. The reported plasma half-life is about 10 hours, which is what drives how often it is redosed. Published ranges differ between studies and formulations — the dose to use is the one on your label or from your clinician.
There is no single answer for Amitriptyline plus TRT. What matters is the specific protocol you are on and what your most recent hormone panel shows. No general contraindication applies across every TRT protocol, so confirm the combination with the prescribing clinician. See the free TRT interaction reference: https://doseroutine.com/trt-supplement-interactions
Pairing Amitriptyline with peptides has to be assessed one peptide at a time, because GLP-1 agonists, secretagogues, healing peptides and melanocortins do not share an interaction profile. Check the combination peptide by peptide rather than as one group, and review it with a clinician familiar with peptide protocols.
With a plasma half-life near 10 hours, once-daily dosing is the usual pattern for Amitriptyline. It is typically taken in the evening. Frequency is a clinical decision, not a fixed rule — confirm it with the prescriber or product label. Comparison of apps that keep a schedule like this: https://doseroutine.com/best-dose-tracking-apps
With a plasma half-life near 10 hours, a single missed dose of Amitriptyline usually has a smaller effect on overall exposure than an irregular pattern of missed doses does. Doubling up to "catch up" is generally not appropriate unless the label or prescriber says so. Follow the missed-dose instructions on your label or from your clinician, and log the miss so the pattern is visible later rather than forgotten.
For Amitriptyline the useful record is the dose, the time it was actually taken, and what else was taken in the same window. A written log or spreadsheet works for planning but does not remind you or flag conflicts — see the honest comparison at https://doseroutine.com/vs/spreadsheet and the wider roundup at https://doseroutine.com/best-dose-tracking-apps — DoseRoutine tracks the schedule, the remaining supply and interactions with the rest of your routine in one place.
Historically dosed at 75–150 mg/day for depression, and at much lower doses (10–50 mg/day) in the fibromyalgia and neuropathic-pain literature reviewed here. Route reported: Oral tablet, as used in the cited pharmacology review and fibromyalgia literature review. Frequency reported: Typically once daily, most often at night because of sedation. These are amounts documented in the cited studies and labels for Amitriptyline — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.
Sources cited on this page
Specific documents referenced by the numbered markers above. Each number matches the marker in the text.
- MedlinePlus(opens in a new tab)U.S. National Library of Medicine · medlineplus.gov/druginfo/meds/a682388.html
- PubChem CID 11065(opens in a new tab)National Center for Biotechnology Information · pubchem.ncbi.nlm.nih.gov/compound/11065
Verify at
Publisher search links for Amitriptyline. These are places to check the information — they are not citations, so they are not numbered.
- Cochrane Library(publisher search, opens in a new tab)Cochrane · publisher search
- DrugBank(publisher search, opens in a new tab)DrugBank Online · publisher search
- Examine.com(publisher search, opens in a new tab)Examine.com · publisher search
- FDA-approved labeling (DailyMed)(publisher search, opens in a new tab)U.S. Food and Drug Administration · publisher search
- Mayo Clinic(publisher search, opens in a new tab)Mayo Clinic · publisher search
- PubMed literature search(publisher search, opens in a new tab)National Library of Medicine · publisher search
- Wikipedia entry(publisher search, opens in a new tab)Wikipedia · publisher search
DoseRoutine compiles summaries from publicly available scientific and regulatory references. Always verify important decisions with a licensed clinician. How we source and review this information.
What is the short answer on Amitriptyline?
Plain-text summary, safe to quote verbatim:
Amitriptyline, commonly known by its former brand name Elavil, is a tricyclic antidepressant (TCA) medication. It was one of the first antidepressants developed and has been in use for several decades. It is typically taken in the evening. The reported plasma half-life is about 10 hours, which shapes dosing frequency.
Source: DoseRoutine — https://doseroutine.com/library/amitriptyline
Amitriptyline cheat sheet
DoseRoutine cheat sheet · Medication
Amitriptyline
Amitriptyline, commonly known by its former brand name Elavil, is a tricyclic antidepressant (TCA) medication. It was one of the first antidepressants developed and has been in use for several decades.
Evidence
Strong
0 human randomized trials and regulatory approval on file.
Studied range
Historically dosed at 75–150 mg/day for depression, and at much lower doses (10–50 mg/day) in the fibromyalgia and neuropathic-pain literature reviewed here
Route
Oral tablet, as used in the cited pharmacology review and fibromyalgia literature review
Frequency studied
Typically once daily, most often at night because of sedation
Half-life
10–28 h
Timing
in the evening
Prescription only (US)Amitriptyline is an FDA-approved tricyclic antidepressant, first approved decades ago and still prescribed off-label for chronic pain conditions such as fibromyalgia, as discussed in the cited review
Studied ranges, not dosing advice. Not medical advice — talk to a clinician. doseroutine.com/library/amitriptyline
Cite this page
Using this in an article, AI answer, or research note? Please attribute:
DoseRoutine. (2026). Amitriptyline — Overview, Benefits & Side Effects. Retrieved from https://doseroutine.com/library/amitriptyline
What compounds are similar to Amitriptyline?
Others in the medication category or studied for the same goals.