This page shows what was measured, who it was measured in, and what that does not settle.
What Amitriptyline does in the body
Amitriptyline blocks the pumps that recycle noradrenaline and serotonin, so more of both stays between nerve cells.
It also blocks several other receptors it was never designed for: the ones that control saliva, pupils, bladder and heart rate, the histamine receptor that makes people drowsy, and the ones that keep blood vessels tight. At low doses those extra effects and the pain pathways are what most people are actually taking it for. Its own label says the mechanism in humans is not known.
Why people take it. Depression — although most prescriptions today are at much lower doses for nerve pain, migraine prevention, irritable bowel syndrome or sleep
What happened in people
At least one adverse event in 55% against 36% on placebo in neuropathic pain trials, number needed to harm 5.2
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
That the licensed antidepressant evidence supports the low-dose analgesic, migraine, bowel and hypnotic uses across a fivefold dose gap
Where it acts
Noradrenaline and serotonin transporters in the central nervous system; muscarinic and histamine receptors throughout the body; and, in overdose, the cardiac fast sodium channel
Kind of result
Symptoms and quality of life
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
Its recorded molecular formula is C20H23N∙HCl, weighing 313.87.
US prescribing information · 4e0f3b15-3621-48a1-9f2b-b0a373920360 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 124 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
Receptor
A receptor is a part of a cell that a signal fits into.
A picture of it, and where the picture fails
A receptor is like a lock waiting for one key.
Where that stops being true. A lock either opens or does not. A receptor can be half-triggered, or worn out.
What people get wrong. Fitting a receptor is read as causing a benefit. It causes a step, and nothing more.
A protein that binds a specific ligand and converts that binding into a cellular response.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 38 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Pain
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer5 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Sleep
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Mood
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer2 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Pain
therapeutic response to the analgesic drugs; pain intensity; reduction in daily genital pain; visual analog scale pain; measuring pain by computerized visual analog scale scoring; chronic post surgical pain
Sleep
objective total sleep time; objective sleep onset latency; self reported total sleep time; self reported sleep onset latency
Mood
hamilton depression rating scale; hamilton depression scale continuous
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
… Waiting for a reviewer
5 registered symptom measure.
— Not recorded
Harms were not a registered measure for this goal.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Efficacy as response rate and acceptability as all-cause discontinuation, across 21 antidepressants in adults with major depressive disorder
✓ The study showed what it set out to show
Who was studied
2018 network meta-analysis of 21 antidepressants (Lancet 2018;391:1357-1366)
How many people
116477
Study design
Systematic review and network meta-analysis of 522 randomised trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Amitriptyline had the highest efficacy odds ratio against placebo of the 21 drugs, 2.13 (95% CrI 1.89 to 2.41), and was one of seven more effective in head-to-head comparison
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Amitriptyline also sat in the group with the highest dropout rates (odds ratios 1.30 to 2.32). Certainty of evidence across the analysis was moderate to very low, and 46 of 522 trials (9%) were at high risk of bias.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 10, 25, 50, 75, 100 and 150 mg, usually taken once daily at night when the sedation is wanted
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
Substantial pain intensity reduction against placebo or an active comparator across seven neuropathic pain conditions
✗ The study did not show it
Who was studied
Cochrane review of amitriptyline for neuropathic pain (Cochrane Database Syst Rev 2015;(7):CD008242)
How many people
1342
Study design
Systematic review of 17 randomised, double-blind trials of at least four weeks
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
No first-tier or second-tier evidence in any condition; only third-tier evidence available, with amitriptyline significantly better than placebo in only two of seven studies reporting useful efficacy data, at very low quality
Repeated elsewhere
Failed to Replicate
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. At least one adverse event in 55% on amitriptyline against 36% on placebo, risk ratio 1.5 (95% CI 1.3 to 1.8), number needed to harm 5.2 (3.6 to 9.1). Most studies were at high risk of bias due to small size; the median parallel-group study had 84 participants and the median cross-over study 36.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 10, 25, 50, 75, 100 and 150 mg, usually taken once daily at night when the sedation is wanted
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
IBS Severity Scoring System score at six months on titrated low-dose amitriptyline against placebo, as second-line treatment for irritable bowel syndrome
Phase 3, randomised, double-blind, placebo-controlled, primary care
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Intention-to-treat difference of −27.0 (95% CI −46.9 to −7.10), p=0.0079, favouring low-dose amitriptyline
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. 46 (20%) discontinued amitriptyline, 30 (13%) for adverse events, against 59 (26%) discontinuing placebo, 20 (9%) for adverse events. Five serious adverse reactions, two on drug and three on placebo. Publicly funded by the NIHR Health Technology Assessment Programme.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 10, 25, 50, 75, 100 and 150 mg, usually taken once daily at night when the sedation is wanted
Interval reported. 95% CI −46
Written into the record, not signed off as a reviewed claim.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.11 registered measures of this kind.
□A number that stands in for healthNo evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse, Rat, Dog. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Amitriptyline
What a person takes: Oral tablet at 10, 25, 50, 75, 100 and 150 mg, usually taken once daily at night when the sedation is wanted.
The measurement behind this step
N-demethylated substantially by CYP2D6 to nortriptyline, itself a licensed antidepressant, so both parent and metabolite circulate in a ratio that varies with CYP2D6 activity. The molecule has no stereocentres and a two-step synthesis, which is why it is among the cheapest prescription drugs in the world.
Getting in
A cheap tablet, usually at a fraction of the licensed dose
Nine cents a tablet, and most prescriptions are for 10 to 50 mg — well below the 75 to 150 mg the depression licence covers.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Dispensed as the hydrochloride. Available strengths span 10 to 150 mg. The licensed indication is depression; the dominant modern uses are neuropathic pain, migraine prophylaxis, irritable bowel syndrome and insomnia, at doses at which transporter occupancy is low and receptor antagonism dominates.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
The liver strips a methyl group and turns amitriptyline into nortriptyline — which is itself sold as a separate antidepressant.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
N-demethylation, substantially by CYP2D6, produces nortriptyline. Anyone taking amitriptyline is carrying both, in a ratio that varies with CYP2D6 activity, which is why a combined plasma assay cannot describe the exposure.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
Noradrenaline and serotonin are both left in the gap between nerve cells for longer. The label calls this "the membrane pump mechanism".
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Inhibition of the membrane pump responsible for uptake of noradrenaline and serotonin in adrenergic and serotonergic neurons. The label states that this "is believed by some to underlie the antidepressant activity", after stating that the mechanism of action in man is not known.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
Muscarinic receptors — dry mouth, constipation, blurred vision. Histamine receptors — drowsiness and weight. Alpha-1 receptors — dizziness on standing. None of it is optional.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Antagonism at muscarinic, histamine H1 and alpha-1 adrenergic receptors accounts for the dose-limiting effects and for most of the reason the SSRIs displaced this class. At low doses these effects arrive before meaningful transporter occupancy does, which is a plausible part of why a 10 mg tablet helps someone sleep.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
In depression, the largest measured effect of any antidepressant
Across 522 trials and 116,477 people, no other antidepressant beat placebo by more. And no group of drugs was harder to stay on.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Efficacy odds ratio against placebo of 2.13 (95% CrI 1.89 to 2.41), the highest of 21 drugs, and one of seven more effective in head-to-head comparison (1.19 to 1.96). Simultaneously in the highest-dropout group (1.30 to 2.32). Certainty of evidence moderate to very low.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
And in overdose, the sodium channel that runs the heart
A large overdose blocks the electrical channel that fires each heartbeat. That is why the label opens its overdose section by saying deaths may occur.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Blockade of the cardiac fast sodium channel widens the QRS complex and shifts its terminal axis rightward — the label names those, with prolonged QT and sinus tachycardia, as specific and sensitive indicators of first-generation tricyclic overdose, while noting their absence is not exclusionary. Cardiac dysrhythmias, severe hypotension, convulsions and coma are the critical manifestations.
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
hamilton depression rating scale
pain intensity
hamilton depression scale continuous
reduction in daily genital pain
quality of life
reflux symptom index
visual analog scale pain
symptom severity scale
central sensitization inventory
measuring pain by computerized visual analog scale scoring
and 1 more.
Measured
Things only a test, a scale or a device shows.
No registered study measured anything of this kind.
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (27)
global response assessment
gastric emptying
gastric volume
headache days per month on the third month of treatment
therapeutic response to the analgesic drugs
calories taken orally
headache days from baseline to month 3 after treatment
visual analog scale
number of reporting a 50 reduction in headache days
severity of headache
objective total sleep time
objective sleep onset latency
self reported total sleep time
self reported sleep onset latency
25 improvement in the ham d
assessment of frequency and severity of adverse events
somatic symptoms scale 8
brief psychiatric rating scale
gerd symptoms
fibromyalgia impact scale
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with depression, per the licence. In practice, adults with nerve pain, migraine, irritable bowel syndrome or insomnia, usually at 10 to 50 mg rather than the 75 to 150 mg antidepressant range. It is on the Beers list of drugs to avoid in older adults because of its anticholinergic load.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Pediatric Use Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS: Clinical Worsening and Suicide Risk ).”
US prescribing information · 4e0f3b15-3621-48a1-9f2b-b0a373920360 · read 2026-08-30
On older people, the label states: “Clinical experience has not identified differences in responses between elderly and younger patients.”
US prescribing information · 4e0f3b15-3621-48a1-9f2b-b0a373920360 · read 2026-08-30
On people who are pregnant, the label states: “Usage in Pregnancy Pregnancy Category C Teratogenic effects were not observed in mice, rats, or rabbits when amitriptyline was given orally at doses of 2 to 40 mg/kg/day (up to 13 times the maximum recommended human dose Based on a maximum recommended amitriptyline dose of 150 mg/day or 3 mg/kg/day for a 50 kg patient. ).”
US prescribing information · 4e0f3b15-3621-48a1-9f2b-b0a373920360 · read 2026-08-30
On people who are breastfeeding, the label states: “Amitriptyline is excreted into breast milk.”
US prescribing information · 4e0f3b15-3621-48a1-9f2b-b0a373920360 · read 2026-08-30
Where the result stopped carrying
The Cochrane review of the drug’s commonest use found no unbiased evidence of benefit in any neuropathic pain condition
Tolerability, not efficacy, is what the SSRIs beat this drug on — and the network meta-analysis confirms both halves of that
The label carries no clinical studies section, no effect size and no numbered structure, so the licensed claim cannot be checked against anything
Overdose is lethal at quantities routinely dispensed, in a population whose condition carries a risk of self-harm
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet at 10, 25, 50, 75, 100 and 150 mg, usually taken once daily at night when the sedation is wanted
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S6.
No source is stored against this line.
What is in the pack
N-demethylated substantially by CYP2D6 to nortriptyline, itself a licensed antidepressant, so both parent and metabolite circulate in a ratio that varies with CYP2D6 activity. The molecule has no stereocentres and a two-step synthesis, which is why it is among the cheapest prescription drugs in the world.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Boxed warning for suicidal thoughts and behaviours in children, adolescents and young adults. Deaths may occur from overdosage with this class of drugs: critical manifestations are cardiac dysrhythmias, severe hypotension, convulsions and coma, with QRS widening and terminal-axis shift as specific indicators, and hospital monitoring is directed as soon as possible after ingestion. Strong antimuscarinic effects — dry mouth, constipation, blurred vision, urinary hesitancy — and antihistaminic sedation and weight gain, and alpha-1-mediated postural hypotension. On the American Geriatrics Society Beers list for older adults. Contraindicated with monoamine oxidase inhibitors and in the acute recovery phase after myocardial infarction.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Amitriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Precautions and Overdosage sectio… · a recorded source, not a stored snapshot
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Amitriptyline appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2193 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
fall — 260 reaction mentions
hypotension — 252 reaction mentions
pain — 239 reaction mentions
depressed level of consciousness — 226 reaction mentions
cognitive disorder — 214 reaction mentions
constipation — 211 reaction mentions
drug hypersensitivity — 207 reaction mentions
toxicity to various agents — 205 reaction mentions
balance disorder — 192 reaction mentions
sedation — 187 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet at 10, 25, 50, 75, 100 and 150 mg, usually taken once daily at night when the sedation is wanted
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
The molecule has no stereocentres and a two-step synthesis, which is why it is among the cheapest prescription drugs in the world.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
234 products list this as an active ingredient in the United States drug directory. 227 of them contain it and nothing else.
FDA National Drug Code directory · 71335-9633 · read 2026-08-29
They are sold as powder, tablet, tablet, coated and tablet, film coated, taken oral.
FDA National Drug Code directory · 71335-9633 · read 2026-08-29
The regulator's established pharmacologic class for it is tricyclic antidepressant [epc].
FDA National Drug Code directory · 71335-9633 · read 2026-08-29
123 published labels name it as an active ingredient. 121 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 4e0f3b15-3621-48a1-9f2b-b0a373920360 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 4e0f3b15-3621-48a1-9f2b-b0a373920360 · read 2026-08-29
Recorded price in US: 0.02994–0.30697 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 106 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Amitriptyline studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the licensed antidepressant evidence supports the low-dose analgesic, migraine, bowel and hypnotic uses across a fivefold dose gap
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That reuptake inhibition explains the antidepressant effect — the label’s own wording is "believed by some"
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the class-level anticholinergic dementia association applies to amitriptyline specifically; the study does not report the molecule individually
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That "endogenous depression is more likely to be alleviated" is a usable clinical distinction; no current diagnostic manual carries that category
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
How fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Amitriptyline are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
A twenty-word indications section and a mechanism "believed by some"
In plain words
The entire licensed indication reads: "For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states." No trial is named, no number is given, and the diagnostic category it uses is not in any current manual.
What was measured
Content of the licensed indications and mechanism statements, against the format of a modern label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The indications section of the amitriptyline hydrochloride label is quoted above in full. The clinical pharmacology section reads: "Amitriptyline hydrochloride is an antidepressant with sedative effects. Its mechanism of action in man is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin... This interference with reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline." The phrase "believed by some" is the weakest mechanistic attribution on any label in this file, and it is more candid than most of them. The document is in the pre-1980s narrative format, with no numbered sections, no clinical studies section and no efficacy table — set against, for example, duloxetine’s Table 8, which prints six placebo-subtracted effect sizes with confidence intervals. This is not evidence that amitriptyline does not work: the 2018 network meta-analysis ranks it first of 21 on efficacy against placebo. It is evidence that the document a prescriber reads carries none of that information, and that a reader cannot check the licensed claim against anything.
Source
Amitriptyline hydrochloride United States prescribing information, Indications and Usage and Clinical Pharmacology sections
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
First of 21 on efficacy, and among the seven worst on staying on it
In plain words
In the largest comparison of antidepressants ever run, amitriptyline had the biggest advantage over placebo of all twenty-one drugs. It was also among the seven people were most likely to stop taking.
What was measured
Efficacy and acceptability odds ratios for amitriptyline among 21 antidepressants across 522 trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The 2018 network meta-analysis included 522 trials and 116,477 participants across 21 antidepressants. All were more effective than placebo, with odds ratios ranging from 2.13 (95% credible interval 1.89 to 2.41) for amitriptyline — the highest of the set — down to 1.37 (1.16 to 1.63) for reboxetine. In the head-to-head studies, amitriptyline was one of seven drugs more effective than the others (range of odds ratios 1.19 to 1.96). On acceptability, amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone and venlafaxine had the highest dropout rates (1.30 to 2.32); amitriptyline is therefore in the top group on one axis and the bottom group on the other. Certainty of evidence across the analysis was moderate to very low and 46 of 522 trials (9%) were at high risk of bias. The tolerability half of that result is the whole reason the SSRIs displaced this drug class, and it was never a claim about efficacy.
Written into the record, not signed off as a reviewed claim
No unbiased evidence for the use it is most often prescribed for
In plain words
Amitriptyline has been a first-line treatment for nerve pain for decades. The Cochrane review of every trial found none that met current standards, and only two of seven studies with usable data showed it beating placebo.
What was measured
Tier of evidence available for amitriptyline in neuropathic pain, and adverse event rate against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The 2015 Cochrane review included 17 randomised double-blind studies of at least four weeks in 1,342 participants across seven neuropathic pain conditions — eight cross-over studies with 302 participants at a median of 36 each, and nine parallel-group studies with 1,040 at a median of 84. The authors graded evidence in three tiers, the first requiring substantial pain reduction as the outcome, intention-to-treat analysis without imputation, at least 200 participants in the comparison, 8 to 12 weeks’ duration and parallel design. There was no first-tier or second-tier evidence for amitriptyline in any neuropathic pain condition; only third-tier evidence was available, and for only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo, at very low quality. More participants had at least one adverse event on drug: 55% against 36% on placebo, risk ratio 1.5 (95% CI 1.3 to 1.8), number needed to harm 5.2 (3.6 to 9.1). The authors’ own conclusion is the honest form of this audit: "The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many people with neuropathic pain. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect."
Written into the record, not signed off as a reviewed claim
ATLANTIS: a genuine positive, in the bowel rather than the brain
In plain words
The largest trial of a tricyclic in irritable bowel syndrome randomised 463 people in general practice to low-dose amitriptyline or placebo. Symptom severity scores were 27 points lower on the drug at six months.
What was measured
IBS Severity Scoring System score difference at six months, low-dose amitriptyline against placebo, 463 patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ATLANTIS (ISRCTN48075063) randomised 463 participants — mean age 48.5 years, 315 (68%) female — between October 2019 and April 2022 to titrated low-dose amitriptyline (232) or placebo (231) as a second-line treatment for irritable bowel syndrome in United Kingdom primary care, with patient-led dose titration. Intention-to-treat analysis of the primary outcome showed a significant difference favouring amitriptyline in IBS Severity Scoring System score at six months: −27.0 (95% CI −46.9 to −7.10, p=0.0079). Forty-six (20%) discontinued amitriptyline, 30 (13%) for adverse events, against 59 (26%) discontinuing placebo, 20 (9%) for adverse events. There were five serious adverse reactions, two on amitriptyline and three on placebo. The trial was funded by the NIHR Health Technology Assessment Programme. Two things make this the most informative positive result on this page: it is publicly funded and independent, and it tested the low-dose off-label use directly rather than borrowing evidence from the antidepressant dose. That is the design the neuropathic pain literature never produced.
Written into the record, not signed off as a reviewed claim
A nine-cent tablet that is lethal in a month’s supply
In plain words
The label’s overdose section opens with the sentence "Deaths may occur from overdosage with this class of drugs." That is not true of any SSRI on this site, and it matters because the condition being treated carries a risk of self-harm.
What was measured
Labelled overdose manifestations and the electrocardiographic markers of tricyclic toxicity
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The overdose section states that deaths may occur, that multiple drug ingestion including alcohol is common in deliberate tricyclic overdose, and that because signs of toxicity develop rapidly, hospital monitoring is required as soon as possible. Critical manifestations are cardiac dysrhythmias, severe hypotension, convulsions and central nervous system depression including coma. Electrocardiographic changes, particularly in QRS axis or width, are described as clinically significant indicators of toxicity, with a rightward axis shift in the terminal QRS complex together with a prolonged QT and sinus tachycardia named as specific and sensitive indicators of first-generation tricyclic overdose — while the label adds that their absence is not exclusionary. The mechanism is blockade of the cardiac fast sodium channel, the same target class as a local anaesthetic. Prolonged PR interval, ST-T wave changes, ventricular tachycardia and fibrillation may also occur. For comparison, venlafaxine’s label describes its own overdose risk as higher than the SSRIs but lower than the tricyclics, which places this drug at the top of that ordering.
Source
Amitriptyline hydrochloride United States prescribing information, Overdosage section; venlafaxine United States prescribing information, Overdosage — Human Experience
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
A class-level dementia signal that this page will not pin on the molecule
In plain words
A very large study found that people with the heaviest cumulative exposure to strongly anticholinergic drugs had about 50% higher odds of a dementia diagnosis, and that anticholinergic antidepressants as a group carried about 29% higher odds. It did not name amitriptyline.
What was measured
That amitriptyline specifically raises dementia risk — an extrapolation from a class-level observational association in which the molecule is not individually reported
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A nested case-control study covering 284,343 case patients and matched controls, 63.1% women, mean age 82.2 years, found the adjusted odds ratio for dementia rising from 1.06 (95% CI 1.03 to 1.09) at the lowest cumulative anticholinergic exposure band (1 to 90 total standardised daily doses) to 1.49 (95% CI 1.44 to 1.54) above 1,095 total standardised daily doses, against no anticholinergic prescriptions in the 1 to 11 years before the index date. Significant increases were found for anticholinergic antidepressants (adjusted OR 1.29, 95% CI 1.24 to 1.34), antiparkinson drugs, antipsychotics, bladder antimuscarinics and antiepileptics, all above 1,095 doses. Results were similar restricting exposure to 3 to 13 and 5 to 20 years before diagnosis, associations were stronger in cases diagnosed before age 80, and the population-attributable fraction for total anticholinergic exposure was 10.3%. Two limits belong on the page. This is observational, and prodromal dementia can itself drive prescriptions for depression, incontinence and sleep, which is reverse causation the design can attenuate but not eliminate. And amitriptyline is not named in the paper’s accessible text — this is a class-level result, and the convention on this site is that a class effect is an inference and not a measurement.
Written into the record, not signed off as a reviewed claim
The low-dose uses borrow their rationale from the high-dose licence
In plain words
Most amitriptyline prescriptions are for 10 to 50 mg, for pain, migraine, bowel symptoms or sleep. The licence is for depression at 75 to 150 mg. The pharmacology at ten milligrams is not the pharmacology the licence was granted on.
What was measured
That the licensed antidepressant evidence supports the low-dose analgesic, migraine, bowel and hypnotic uses — a transfer of evidence across a fivefold dose difference and four unrelated conditions
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
At 10 to 25 mg, plasma concentrations sit well below those associated with meaningful monoamine transporter occupancy, and the antihistaminic and antimuscarinic effects dominate — which is consistent with the sedation being the most reliable effect at those doses. The Cochrane review of neuropathic pain notes explicitly that "neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants", and then finds no first- or second-tier evidence that this one does. The one place where the low-dose use has been tested properly and won is irritable bowel syndrome, in ATLANTIS. The pattern across this file is consistent: where somebody funded a trial of the actual low-dose use, the answer was sometimes yes and sometimes no, and where nobody did, the practice continued on inference. Amitriptyline is the drug where both outcomes are visible at once.
This order is fixed in code and does not count clicks or time on the page.
What is not here
4 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
The tricyclic with the highest efficacy odds ratio against placebo of all 21 drugs in the 2018 network meta-analysis (2.13, 95% CrI 1.89 to 2.41) and one of the seven highest dropout rates, whose 1961 label runs to twenty words and attributes its mechanism to what "is believed by some", and for whose commonest modern use — neuropathic pain — the 2015 Cochrane review of 17 trials in 1,342 patients found no first-tier or second-tier evidence and adverse events in 55% against 36% on placebo.
Recorded evidence blocks (13)
Q2
What did Amitriptyline's largest trial (494 people) and its longest (11 years) measure?
494 people in Amitriptyline's largest registered study, 11 years in its longest registered window, measuring AUC0-∞ of amitriptyline (area under the concentration-time curve of amitriptyline in plasma over the time interval from 0 extrapolated to infinity). ClinicalTrials.gov · 2026-09-01
26 phase2, 21 phase3, 21 phase4, 15 na, 6 phase1, 2 na or unstated, 1 early phase1; NCT00312260; 2017-03-02; no ageing endpoint recorded. Last human test completed 2025, NCT03472092.
Interpretation These counts include studies where Amitriptyline was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase2
26
phase3
21
phase4
21
na
15
phase1
6
na or unstated
2
2 more recorded rows
early phase1
1
Last recorded human testNCT03472092
2025-06-30
recorded 2026-09-01 · last checked 2026-09-04
Q3
From mouse to human: where has Amitriptyline shown lifespan?
AUC0-∞ of amitriptyline (area under the concentration-time curve of amitriptyline in plasma over the time interval from 0 extrapolated to infinity) — the recorded outcome words.
Show the evidence
mouse
lifespan
rat
lifespan
dog
lifespan
humanNCT02256878
biomarker; AUC0-∞ of amitriptyline (area under the concentration-time curve of amitriptyline in plasma over the time interval from 0 extrapolated to infinity); 85
recorded 2026-09-01 · last checked 2026-09-04
Q4
12 of Amitriptyline's trials stopped: futility/efficacy, accrual/recruitment, funding/business, other?
futility/efficacy (2), accrual/recruitment (3), funding/business (1) and other (6): Amitriptyline's stop wording, clustered. ClinicalTrials.gov · 2026-09-01
"Futility; study coordinator left and were unable to continue data collection; missing data"; 12 of 85 registered studies
Show the evidence
Trial
NCT00220844
terminated; "Futility; study coordinator left and were unable to continue data collection; missing data"
NCT00862095
terminated; "inadequate enrollment, insufficient funds to continue enrollment"
NCT01581281
terminated; "Interim assessment provided sufficient data to answer study questions"
NCT02090998
terminated; "no patients during covid pandemic"
NCT02139098
terminated; "Recruiting problems because of the time expenditure required for participating and the strict criteria of inclusion and exclusion"
NCT02190526
withdrawn; "Study stopped due to lack of volunteer patients."
6 further recorded trials
NCT02434523
terminated; "concern regarding study design"
NCT02552225
terminated; "Funding was not obtained so the study could not be continued after the Covid pause."
NCT03096444
terminated; "Efficacy was not seen after interim analysis"
NCT03591458
terminated; "Slow subject enrollment, unable to complete trial in a timely manner"
NCT04725383
terminated; "The PI is retiring."
NCT06417684
withdrawn; "Unable to gain interest among colleagues to help recruit participants."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Amitriptyline used Amitriptyline 25 MG — over how long?
5 recorded entries; human; also "Amitriptyline 25 MG", "Amitriptyline 50 MG", "Amitriptyline 25 Mg Oral Tablet"
Show the evidence
human
NCT05110144
Amitriptyline 25 MG
NCT05110144
Amitriptyline 50 MG
NCT05759845
Amitriptyline 25 Mg Oral Tablet
NCT05759845
topiramate 25mg plus amitriptyline 25mg
NCT05867550
Amitriptyline Hydrochloride 25 MG
recorded 2026-09-01 · last checked 2026-09-04
Q6
More Amitriptyline was worse in human: at what point?
U-shaped in human: "However, the therapeutic efficacy of these drugs in BMS frequently exhibits a non-sigmoid (U-shaped or bell-shaped) dose-response relationship, indicating a clinically effective dose that is often considerably lower than those used for their primary indications and challenging conventional pharmacological assumptions.…" Europe PMC · dose-response search · 2026-02-26
6 recorded sentences naming Amitriptyline; U-shaped, hormesis, Dose-response, dose-response
Show the evidence
U-shapedPMID 41156152
"However, the therapeutic efficacy of these drugs in BMS frequently exhibits a non-sigmoid (U-shaped or bell-shaped) dose-response relationship, indicating a clinically effective dose that is often considerably lower than those used for their primary indications and challenging conventional pharmacological assumptions. <b>Method</b>: This paper synthesizes existing pharmacological knowledge to…"
hormesisPMID 41156152
"The general non-dose-dependency for both drugs is further explained by phenomena such as multiple binding sites with differing affinities, receptor desensitization/downregulation, activation of counter-regulatory mechanisms, and hormesis. <b>Discussion</b>: The observed non-linear dose-response curves for amitriptyline and aripiprazole in BMS underscore the inadequacy of a "one-size-fits-all"…"
U-shaped
PMID 24447704
"A U-shaped concentration-dependent response curve was observed in ACTH level in response to amitriptyline exposure."
PMID 24447704
"Correspondingly, hydroxyl radical formation and lipid peroxidation indices changed in similar U-shaped concentration-dependent patterns, which together the results of antioxidant parameters suggested induction of oxidative stress in embryos exposed to amitriptyline at high concentrations."
Dose-responsePMID 41741691
"Dose-response experiments using the tricyclic antidepressant, amitriptyline (0.3-3.0 mg/kg), monoamine oxidase inhibitor, moclobemide (3.0-10.0 mg/kg) and serotonin specific re-uptake inhibitor, sertraline (1.0-10.0 mg/kg) were performed."
dose-responsePMID 41156152
"It focuses on their specific interactions with key neurotransmitter systems and receptors, particularly N-methyl-D-aspartate (NMDA) receptors and dopamine D2 receptors, to explain the observed non-linear dose-response and the importance of identifying a personalized therapeutic window. <b>Result</b>: Amitriptyline demonstrates efficacy in BMS at low doses (e.g., 25 mg), primarily through its…"
recorded 2026-02-26 · last checked 2026-09-04
Q7
Which of 25 improvement in the ham d, assessment of frequency and severity of adverse events and awake objective cough frequency did Amitriptyline's trials measure?
25 improvement in the ham d, assessment of frequency and severity of adverse events and awake objective cough frequency lead 38 outcome terms across Amitriptyline's trials. ClinicalTrials.gov · 2026-09-01
headache days per month on the third month of treatment, hamilton depression rating scale, therapeutic response to the analgesic drugs, calories taken orally, headache days from baseline to month 3 after treatment and visual analog scale follow.
Show the evidence
global response assessment
1
gastric emptying
1
gastric volume
1
headache days per month on the third month of treatment
1
hamilton depression rating scale
1
therapeutic response to the analgesic drugs
1
14 more recorded rows
calories taken orally
1
headache days from baseline to month 3 after treatment
1
visual analog scale
1
number of reporting a 50 reduction in headache days
1
severity of headache
1
pain intensity
1
hamilton depression scale continuous
1
reduction in daily genital pain
1
objective total sleep time
1
objective sleep onset latency
1
self reported total sleep time
1
self reported sleep onset latency
1
quality of life
1
25 improvement in the ham d
1
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which of Amitriptyline's 11 ongoing trials reports first?
Change in awake objective cough frequency (at 4 & 8 weeks); Changes in VAS score for pain intensity from baseline to 2 weeks, 4 weeks and 8 weeks after randomization.; latest 2033-06
Show the evidence
Trial
NCT05110144
"Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough"; n 50; "Change in awake objective cough frequency (at 4 & 8 weeks)"; 2026-12
NCT05120934
"Efficacy of Two Doses of Duloxetine & Amitriptyline in Interstitial Lung Disease-related Cough"; n 25; "Change in awake objective cough frequency (at 4 & 8 weeks)"; 2026-10
NCT05279963
"EA for BPS: An RCT and Study for Central Mechanism"; n 84; "Changes in VAS score for pain intensity from baseline to 2 weeks, 4 weeks and 8 weeks after randomization."; 2025-01-23
NCT05889624
"Responding With Evidence and Access for Childhood Headaches"; n 400; "Change in number of headache days"; 2027-12-31
NCT06312813
"Evaluating Use of Topical Imipramine and Amitriptyline in Reducing Ultraviolet B Light-Induced Redness in Patients With Rosacea"; n 48; "Difference in redness of Ultraviolet B induced erythema with 4% imipramine"; 2028-12-01
NCT06499116
"Comparison of the Effectiveness of First-line Preventive Treatment of Migraine in Primary Care"; n 460; "To evaluate the effectiveness of the most frequently used drugs in primary care for the preventive treatment of migraine according to the reduction in monthly migraine days, comparing amitriptyline, flunarizine and topiramate with…"; 2026-12
5 further recorded trials
NCT07296770
"An Artificial Intelligence Driven Approach to Optimize Patient Selection for a Transitional Pain Service"; n 126; "Proportion of Patients With Chronic Post-Surgical Pain"; 2028-07-01
NCT07556718
"Amitriptyline for IBS-like Symptoms in Quiescent Crohn's Disease"; n 100; "Safety reported as the proportion of participants experiencing a serious adverse event (SAE),"; 2029-12
NCT07640061
"Pilot Studies Testing the Use of Oral Amitriptyline in Reducing Localized Burn Injury-induced Microvesicle Particle Release"; n 20; "Change from Baseline in MVP Release in Skin from a localized thermal burn injury in response to oral amitriptyline versus placebo as measured by skin biopsy"; 2033-06
NCT07655440
"Comparing Migraine Preventive Therapies vs. Anti-CGRP Therapies for Tinnitus in Patients With Migraine (COMPACT-PM)"; n 120; "Change in Tinnitus Functional Index (TFI) Score"; 2031-07
NCT07716722
"Pilot Studies Blocking Injury-Induced MVP Release in Skin Using Topical Amitriptyline"; n 50; "Change in the amount of microvesicle particles generated in skin from localized thermal burn injury over untreated skin."; 2032-07
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which 31 trials of Amitriptyline posted no result?
Posted no result
31 of 31 completed trials
Registrations
NCT00000817, NCT00000793, NCT01049347, NCT00000428, NCT00029497 and NCT00381199, and 25 more
Completion dates
oldest 1997-05; newest 2024-02-29
Show the evidence
Trial
NCT00000817
1997-05
NCT00000793
1997-10
NCT01049347
2000-05
NCT00000428
2004-03
NCT00029497
2004-06
NCT00381199
2007-03
14 further recorded trials
NCT00351910
2007-04
NCT00006428
2007-05
NCT00564525
2007-06
NCT00515229
2007-07
NCT00355277
2007-12
NCT00370656
2009-05
NCT01566825
2009-05
NCT00766350
2010-10
NCT01306708
2011-12
NCT01357031
2012-12
NCT01161017
2014-05
NCT01561209
2014-06
NCT01869907
2014-08
NCT02127736
2014-09
Q10
At the median, Amitriptyline's trials enrolled 60 people — anything larger?
Median enrolment
60
Largest enrolment
494
Registered trials counted
84
Q11
What do 2193 spontaneous reports say about Amitriptyline — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Amitriptyline appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2193 reaction mentions were counted: fall 260; hypotension 252; pain 239; depressed level of consciousness 226. open-targets-adr · CHEMBL1200964 · 2026-06-24
Show the evidence
fall
260
hypotension
252
pain
239
depressed level of consciousness
226
cognitive disorder
214
constipation
211
4 more recorded rows
drug hypersensitivity
207
toxicity to various agents
205
balance disorder
192
sedation
187
recorded 2026-06-24 · last checked 2026-09-04
Q12
Amitriptyline and cytochrome P450: shared by which compounds?
cytochrome P450 appear in Amitriptyline's recorded interaction sentences, 3 in all. openfda-label+europepmc · 2026-08-26
Interpretation drug_interactions
Show the evidence
cytochrome P450
drug_interactions
Drugs Metabolized by P450 2D6 The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of Caucasians are so called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available.
drug_interactions
The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide).
drug_interactions
Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug.
recorded 2026-08-26 · last checked 2026-09-04
Q13
Was Amitriptyline studied with fasting and exercise?
fasting and exercise are named in Amitriptyline's label sentences: "This clinical trial was designed to evaluate and compare the relative bioavailability with regard to dose proportionality between the two marketed strengths of amitriptyline hydrochloride tablets after a single-dose, oral administration under fasting conditions in healthy, male, Korean volunteers." openfda-label+europepmc · 2026-08-26
2 recorded statements; fasting, exercise
Show the evidence
fasting
This clinical trial was designed to evaluate and compare the relative bioavailability with regard to dose proportionality between the two marketed strengths of amitriptyline hydrochloride tablets after a single-dose, oral administration under fasting conditions in healthy, male, Korean volunteers.
exercise
All participants received background multimodal pain management consisting of amitriptyline and aerobic exercise.
recorded 2026-08-26 · last checked 2026-09-04
Q14
What is recorded about Amitriptyline and autophagy?
"The dose and time-dependent upregulation of the autophagy marker LC3II and the autophagy receptor p62, with the accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to the amitriptyline." — where Amitriptyline and autophagy appear together. Europe PMC · pathway abstract search · 2024-09-27
autophagy, mTOR; PMID 39408742, 33070168
Show the evidence
autophagy
PMID 39408742
"The dose and time-dependent upregulation of the autophagy marker LC3II and the autophagy receptor p62, with the accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to the amitriptyline."
"Dose and time-dependent upregulation of the autophagy markers LC3II and autophagy receptor p62, with accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to amitriptyline."
"Decrease viability and clonogenic activity were still observed in autophagy deficient Atg5 -/- MEF and following pre-treatment of SH-SY5Y culture with the autophagy inhibitor chloroquine suggesting that the amitriptyline’s effects on cell proliferation were not caused by the modulation of autophagy."
mTORPMID 33070168
"Amitriptyline interfered with the fusion of autophagosome and lysosome through the activation of PI3K/Akt/mTOR pathway and Beclin 1 acetylation, and regulated lysosome positioning by increasing the interaction between proteins Arl8, SKIP, and kinesin."
recorded 2024-09-27 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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