This page shows what was measured, who it was measured in, and what that does not settle.
What Nortriptyline does in the body
Nortriptyline blocks the pump that recycles noradrenaline back into nerve cells, and to a lesser extent the serotonin pump.
It is the compound your liver makes out of amitriptyline, so it does much the same job with less of the dry mouth, constipation and drowsiness. Its label is unusual in one way: above a certain dose it tells the prescriber to measure the drug in your blood and keep it inside a range, because too much appears to work no better than too little.
Why people take it. Depression — and, off-label, nerve pain, migraine prevention and helping people stop smoking
What happened in people
No first-tier or second-tier evidence for neuropathic pain across six trials and 310 participants
✎ 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.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · a recorded source, not a stored snapshot
First approved in the United States in 1964; brands discontinued and only 33 generic products listed, against 113 for amitriptyline
Where it acts
Noradrenaline transporters in the central nervous system; muscarinic, histaminergic and alpha-1 receptors elsewhere; 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.
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 110 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 17 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
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 reviewer4 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.
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 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
Mood
hamilton rating scale for depression range; hamilton depression scale; hamilton depression rating scale; hamilton depression scale continuous; depressive symptoms
Pain
average pain; chronic post surgical pain
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
4 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.
Relationship between plasma nortriptyline concentration and reduction in a psychiatric-interview depression rating after two weeks of treatment
✓ The study showed what it set out to show
Who was studied
Åsberg M et al., Br Med J 1971;3:331-334 — the plasma level study
How many people
29
Study design
Open pharmacokinetic-pharmacodynamic study in psychiatric inpatients
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
A curved relationship: amelioration most pronounced in the intermediate plasma range of 50 to 139 ng/mL and slight both at lower and at higher levels
Repeated elsewhere
Partially 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. Twenty-nine inpatients, all diagnosed with endogenous depression, at a single centre, over two weeks, with no placebo arm and no blinding described in the abstract. This is the entire origin of the plasma range that has appeared on the label for over half a century.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule at 10, 25, 50 and 75 mg, and an oral solution; usually 25 mg three or four times daily, or the total daily dose given once, per the label
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · a recorded source, not a stored snapshot
At least 50% pain intensity reduction, or Patient Global Impression of Change much or very much improved, in chronic neuropathic pain
✗ The study did not show it
Who was studied
Cochrane review of nortriptyline for neuropathic pain (Cochrane Database Syst Rev 2015;(1):CD011209)
How many people
310
Study design
Systematic review of six randomised, double-blind trials of at least two weeks
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
No study provided first- or second-tier evidence for any outcome; third-tier evidence indicated similar efficacy to gabapentin, morphine, chlorimipramine, amitriptyline and to placebo, 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. All studies had one or more sources of potential major bias, five of six used a cross-over design, and adverse event reporting was inconsistent and fragmented. More participants reported adverse events on nortriptyline than on placebo. No study addressed trigeminal neuralgia; no serious adverse events or deaths were reported.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule at 10, 25, 50 and 75 mg, and an oral solution; usually 25 mg three or four times daily, or the total daily dose given once, per the label
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · a recorded source, not a stored snapshot
Long-term smoking abstinence on nortriptyline against placebo, within a review covering all antidepressants
✓ The study showed what it set out to show
Who was studied
Cochrane review of antidepressants for smoking cessation (Cochrane Database Syst Rev 2020;(4):CD000031)
How many people
975
Study design
Systematic review and meta-analysis of 115 randomised studies
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Risk ratio 2.03 (95% CI 1.48 to 2.78), I²=16%, across 6 studies and 975 participants
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. Whether bupropion or nortriptyline is more effective could not be determined: RR 1.30 favouring bupropion, 95% CI 0.93 to 1.82, 3 studies, 417 participants. Nortriptyline holds no smoking cessation licence in any jurisdiction. Findings were sparse and inconsistent on whether either drug helped people with current or previous depression in particular.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule at 10, 25, 50 and 75 mg, and an oral solution; usually 25 mg three or four times daily, or the total daily dose given once, per the label
Interval reported. 95% CI 1
Written into the record, not signed off as a reviewed claim.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · 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.10 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. 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
Nortriptyline
What a person takes: Oral capsule at 10, 25, 50 and 75 mg, and an oral solution; usually 25 mg three or four times daily, or the total daily dose given once, per the label.
The measurement behind this step
Nortriptyline is itself the active metabolite of amitriptyline, and is further metabolised to 10-hydroxynortriptyline. CYP2D6 activity drives large between-person variation in plasma concentration at a given dose, which is the reason the label asks for plasma monitoring above 100 mg/day and caps the dose at 150 mg/day.
Getting in
A capsule — and the compound your body makes from amitriptyline
Anyone taking amitriptyline is already producing nortriptyline. Taking it directly skips a conversion step whose speed varies a lot between people.
╌╌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
Nortriptyline is the N-demethylated metabolite of amitriptyline, formed substantially by CYP2D6, and is marketed as a drug in its own right. Removing that single methyl group reduces muscarinic and histaminergic affinity and shifts reuptake selectivity toward noradrenaline.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · a recorded source, not a stored snapshot
The same dose gives different people very different levels
How much drug ends up in your blood from a given tablet varies several-fold between people. That is why this label asks for a blood test.
──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
The 1971 study behind the label’s plasma range noted that large individual variation in tricyclic pharmacokinetics makes prediction of plasma level from dose in a given individual virtually impossible without knowing the rate of elimination and apparent volume of distribution. CYP2D6 activity is the principal source of that variation.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · a recorded source, not a stored snapshot
It stops noradrenaline being vacuumed back into the nerve cell, leaving more in the gap. It does the same to serotonin, more weakly than its parent does.
╌╌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 noradrenaline transporter with weaker serotonin transporter activity than amitriptyline. The label describes this in period language as interference with the transport, release and storage of catecholamines, and states plainly that the mechanism of mood elevation by tricyclics is at present unknown.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · a recorded source, not a stored snapshot
Too much appears to work no better than too little
Unusually, pushing the dose higher does not keep helping. The improvement was best in the middle of the blood-level range and slight at both ends.
╌╌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
In 29 inpatients, amelioration was most pronounced between 50 and 139 ng/mL and slight both below and above. The authors attributed the upper fall-off to a phenothiazine-like receptor blockade being added to reuptake inhibition at higher concentrations, and concluded that there are two routes to therapeutic failure: too low a level and too high a one.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · a recorded source, not a stored snapshot
Its clearest randomised result is helping people stop smoking — roughly doubling quit rates. For nerve pain, where guidelines recommend it, the evidence is much thinner.
──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
Smoking cessation against placebo: risk ratio 2.03 (95% CI 1.48 to 2.78), 6 studies, 975 participants, in an indication it holds nowhere. Neuropathic pain: six studies, 310 participants, no first- or second-tier evidence, with the review naming duloxetine and pregabalin as the better-supported alternatives.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · a recorded source, not a stored snapshot
Losing the methyl group made it easier to tolerate day to day. It did nothing to the danger of taking too much at once.
╌╌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
The overdose section names cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary oedema, convulsions and coma as critical manifestations, with QRS axis or width change as the clinically significant indicator. The mechanism, cardiac fast sodium channel blockade, is shared with amitriptyline.
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · 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 rating scale for depression range
hamilton depression scale
average pain
hamilton depression rating scale
hamilton depression scale continuous
swiss spinal stenosis questionnaire
quality of life instrument scores
psychological well being
symptom response
chronic post surgical pain
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 (7)
time of retention
25 improvement in the ham d
assessment of frequency and severity of adverse events
response to treatment
serious adverse events
depressive symptoms
tinnitus functional index
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. The label states it is not recommended for children. In practice it is also used for neuropathic pain and migraine prevention, and it has better trial evidence for helping people stop smoking than for either.
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: “Safety and effectiveness in the pediatric population have not been established ( see BOX WARNING and WARNINGS - Clinical Worsening and Suicide Risk ).”
US prescribing information · 09a54dbd-6bde-3083-e063-6394a90a5297 · read 2026-08-30
On older people, the label states: “Clinical studies of nortriptyline hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · 09a54dbd-6bde-3083-e063-6394a90a5297 · read 2026-08-30
On people who are pregnant, the label states: “Use in Pregnancy Safe use of nortriptyline hydrochloride during pregnancy and lactation has not been established; therefore, when the drug is administered to pregnant patients, nursing mothers, or women of childbearing potential, the potential benefits must be weighed against the possible hazards.”
US prescribing information · 09a54dbd-6bde-3083-e063-6394a90a5297 · read 2026-08-30
Where the result stopped carrying
The Cochrane review of neuropathic pain named duloxetine and pregabalin as better-supported alternatives and recommended against first-line use
The label carries no clinical studies section, no effect size and no trial reference for its licensed indication
The overdose profile is unchanged from amitriptyline: deaths may occur, with cardiac dysrhythmias, shock and pulmonary oedema among the critical manifestations
It remains on the American Geriatrics Society Beers list despite being the less anticholinergic tricyclic
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 capsule at 10, 25, 50 and 75 mg, and an oral solution; usually 25 mg three or four times daily, or the total daily dose given once, per the label
✎ 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
Nortriptyline is itself the active metabolite of amitriptyline, and is further metabolised to 10-hydroxynortriptyline.
✎ 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. The rest of the recorded wording: CYP2D6 activity drives large between-person variation in plasma concentration at a given dose, which is the reason the label asks for plasma monitoring above 100 mg/day and caps the dose at 150 mg/day.
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; not recommended for children. Deaths may occur from overdosage with this class of drugs, with cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary oedema, convulsions and coma among the critical manifestations, and QRS axis or width change as the electrocardiographic indicator. Anticholinergic effects — dry mouth, constipation, blurred vision, urinary hesitancy — are present though less pronounced than with amitriptyline, along with sedation and postural hypotension. On the American Geriatrics Society Beers list for older adults. Lower dosages are directed for elderly and adolescent patients. Contraindicated with monoamine oxidase inhibitors, with 14 days required in either direction.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Nortriptyline hydrochloride United States prescribing information — Indications and Usage, Clinical Pharmacology, Warnings, Dosage and Administration and Ove… · 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.
Nortriptyline appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 881 reaction mentions were counted. One report can name several reactions.
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 capsule at 10, 25, 50 and 75 mg, and an oral solution; usually 25 mg three or four times daily, or the total daily dose given once, per the label
✎ 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
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: CYP2D6 activity drives large between-person variation in plasma concentration at a given dose, which is the reason the label asks for plasma monitoring above 100 mg/day and caps the dose at 150 mg/day.
No source is stored against this line.
What is recorded as being sold
94 products list this as an active ingredient in the United States drug directory. 94 of them contain it and nothing else.
FDA National Drug Code directory · 75907-071 · read 2026-08-29
They are sold as capsule, powder and solution, taken oral.
FDA National Drug Code directory · 75907-071 · read 2026-08-29
The regulator's established pharmacologic class for it is tricyclic antidepressant [epc].
FDA National Drug Code directory · 75907-071 · read 2026-08-29
58 published labels name it as an active ingredient. 58 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 09a54dbd-6bde-3083-e063-6394a90a5297 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 09a54dbd-6bde-3083-e063-6394a90a5297 · read 2026-08-29
Nortriptyline Hydrochloride is capsules at Capsules equivalent to 10 mg, 25 mg, 50 mg or 75 mg base, recorded as prescription product; fda label in effect 2026-01-13 in the United States.
US prescribing information · 017f7717-e160-4142-9a5a-1a2bd9776707 · read 2026-08-27
Recorded price in US: 0.11109–0.25733 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 18 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
Recorded price in US: 0.26358 USD per one millilitre, across 2 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 Nortriptyline 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 a plasma window derived from 29 patients in 1971 generalises to the population now prescribed the drug — it has never been re-derived at modern scale
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 guideline recommendation for neuropathic pain in Europe, the United Kingdom and the United States reflects an evidence base; the Cochrane review found none above third tier
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 lower anticholinergic load translates into better outcomes in older adults, which no head-to-head outcome trial has tested
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 antidepressant efficacy of the tricyclic class transfers to this molecule specifically; nortriptyline was not among the 21 drugs in the 2018 network meta-analysis
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 Nortriptyline 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.
The only antidepressant with a plasma window on its label — from 29 patients in 1971
In plain words
Above 100 mg a day, the label tells the prescriber to measure the drug in your blood and keep it between 50 and 150 nanograms per millilitre. That range comes from a single study of 29 inpatients published in 1971.
What was measured
Therapeutic plasma concentration range on the label, and the sample size and design of the study it derives from
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The dosage section reads: "When doses above 100 mg daily are administered, plasma levels of nortriptyline should be monitored and maintained in the optimum range of 50 to 150 ng/mL. Doses above 150 mg/day are not recommended." No other antidepressant in this file carries an equivalent instruction. The underlying study is Åsberg and colleagues, BMJ 1971: plasma concentration and therapeutic effect after two weeks of treatment in 29 psychiatric inpatients, all diagnosed with endogenous depression, with improvement rated on a psychiatric interview scale. The relationship was curved — amelioration was most pronounced in the intermediate range of 50 to 139 ng/mL and slight both below and above it — and the authors proposed that at higher concentrations a phenothiazine-like receptor blockade is added to the reuptake inhibition. Their conclusion was that there are two ways to fail with nortriptyline, too little and too much, and that dose cannot predict plasma level in an individual. That is a real and unusual finding. It is also 29 patients, two weeks, one centre, and 1971, and it has been carried on the label for over half a century without being re-derived at modern scale.
Written into the record, not signed off as a reviewed claim
Recommended in three continents’ guidelines, with no first- or second-tier evidence
In plain words
Nortriptyline is recommended for nerve pain in European, British and American guidelines. The Cochrane review found six trials totalling 310 people, none of which met current evidence standards, and concluded it should not be first-line.
What was measured
Tier of evidence available across six trials and 310 participants, against the guideline status of the drug
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The 2015 Cochrane review included six randomised double-blind studies of at least two weeks treating 310 participants with various neuropathic pain conditions — five cross-over and one parallel-group, with treatment periods of three to eight weeks. All studies had one or more sources of potential major bias. No study provided first- or second-tier evidence for any outcome. Only one study reported the primary outcome of at least 50% pain reduction, and it gave no indication that either nortriptyline or gabapentin was more effective in postherpetic neuralgia at very low quality. Third-tier evidence in individual studies indicated similar efficacy to gabapentin, morphine, chlorimipramine and amitriptyline — and to placebo — in the conditions studied. More participants reported adverse events on nortriptyline than on placebo. No study addressed trigeminal neuralgia. The authors’ conclusion names the alternatives directly: "The results of this review do not support the use of nortriptyline as a first line treatment. Effective medicines with much greater supportive evidence are available, such as duloxetine and pregabalin." The review’s own background notes that nortriptyline is recommended in European, United Kingdom and United States guidelines, which is the gap this audit is about.
Written into the record, not signed off as a reviewed claim
Its strongest trial result is for an indication it does not hold anywhere
In plain words
Nortriptyline roughly doubles the chance of quitting smoking against placebo, across six trials and 975 people. It is not licensed for smoking cessation in any country.
What was measured
Risk ratio for long-term smoking cessation, nortriptyline against placebo, across six trials and 975 participants
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The 2020 Cochrane review of antidepressants for smoking cessation included 115 studies. It found evidence that nortriptyline aided smoking cessation compared with placebo, risk ratio 2.03 (95% CI 1.48 to 2.78, I²=16%, 6 studies, 975 participants). There was insufficient evidence to determine whether bupropion or nortriptyline was the more effective: the head-to-head comparison gave a risk ratio of 1.30 favouring bupropion, 95% CI 0.93 to 1.82, across three studies and 417 participants. The same review found high-certainty evidence for bupropion against placebo (RR 1.64, 95% CI 1.52 to 1.77, 45 studies, 17,866 participants), no evidence of benefit for St John’s wort, the SSRIs or the monoamine oxidase inhibitors, and that bupropion is less effective than varenicline. Findings were sparse and inconsistent on whether either drug helped people with current or previous depression in particular. Nortriptyline’s cleanest positive result against placebo is in a condition it has never been licensed for, while the use it is guideline-recommended for has no evidence above third tier.
Written into the record, not signed off as a reviewed claim
A 1964 label describing pigeons and pressor responses
In plain words
The pharmacology section states that the mechanism of mood elevation by tricyclics is at present unknown, then describes results from operant conditioning experiments in rats and pigeons and from pressor-response tests. It has not been rewritten.
What was measured
Content of the licensed indication and mechanism statements, and the absence of any efficacy figure on the document
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The clinical pharmacology section reads: "The mechanism of mood elevation by tricyclic antidepressants is at present unknown. Nortriptyline hydrochloride is not a monoamine oxidase inhibitor. It inhibits the activity of such diverse agents as histamine, 5-hydroxytryptamine, and acetylcholine. It increases the pressor effect of norepinephrine but blocks the pressor response of phenethylamine. Studies suggest that nortriptyline hydrochloride interferes with the transport, release, and storage of catecholamines. Operant conditioning techniques in rats and pigeons suggest that nortriptyline hydrochloride has a combination of stimulant and depressant properties." The indications section is two sentences and names a diagnostic category — endogenous depression — that no current manual carries. There is no clinical studies section, no effect size and no numbered structure. The important point is not that the document is old-fashioned but that a reader has nothing to check: the licensed claim is unaccompanied by any number, in contrast to every post-1990 label in this file. Nortriptyline was also not among the 21 drugs assessed in the 2018 network meta-analysis, so there is no modern comparative efficacy figure for it either.
Source
Nortriptyline 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
Less anticholinergic than its parent, and still lethal in overdose
In plain words
Nortriptyline is chosen over amitriptyline because it causes less dry mouth, constipation and drowsiness. It carries exactly the same overdose danger: the label opens its overdose section by saying deaths may occur.
What was measured
Labelled overdose manifestations and electrocardiographic indicators, against those of the parent compound
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 from overdosage with this class of drugs, that multiple drug ingestion including alcohol is common in deliberate tricyclic overdose, and that hospital monitoring is required as soon as possible because signs of toxicity develop rapidly. Critical manifestations are cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary oedema, convulsions and central nervous system depression including coma — a slightly broader list than amitriptyline’s, which does not name shock, heart failure or pulmonary oedema. Changes in the electrocardiogram, particularly in QRS axis or width, are named as clinically significant indicators of toxicity. The mechanism is cardiac fast sodium channel blockade, which the demethylation that produced nortriptyline does not remove. The tolerability advantage over amitriptyline is real and it operates entirely at therapeutic doses; it does nothing at toxic ones.
Source
Nortriptyline hydrochloride United States prescribing information, Overdosage section
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
Preferred in older people on a comparison nobody ran
In plain words
Nortriptyline is the tricyclic recommended for older adults because it is less anticholinergic than amitriptyline. That is a pharmacological comparison, not a clinical trial, and the drug is still on the list of medicines to avoid in older adults.
What was measured
That nortriptyline’s lower receptor-level anticholinergic load translates into better clinical outcomes in older adults — a pharmacological inference that no head-to-head outcome trial has tested
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The preference rests on receptor pharmacology — removing the N-methyl group reduces muscarinic and histaminergic affinity substantially — and on the resulting side-effect profile, not on a head-to-head outcome trial in older adults. No such trial is cited on the label, which offers only the dosing instruction that lower than usual dosages are recommended for elderly patients and adolescents, at 30 to 50 mg/day. Nortriptyline nonetheless appears on the American Geriatrics Society Beers Criteria list of potentially inappropriate medications in older adults, on the same anticholinergic grounds as amitriptyline. The large nested case-control study of anticholinergic exposure and dementia reported the anticholinergic antidepressants as a class at an adjusted odds ratio of 1.29 (95% CI 1.24 to 1.34) at the highest cumulative exposure, without naming individual molecules — so it neither confirms nor exonerates this one. Being the safer member of a class on the avoid-in-older-adults list is a meaningful improvement and is not the same as being safe.
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 active metabolite of amitriptyline, sold separately, and the only antidepressant whose label directs plasma monitoring to an optimum range of 50 to 150 ng/mL — a window derived from a 1971 study of 29 inpatients — which the 2015 Cochrane review found had no first-tier or second-tier evidence in any neuropathic pain condition across six trials and 310 participants, while a 2020 Cochrane review found it roughly doubled smoking quit rates (RR 2.03, 95% CI 1.48 to 2.78) in an indication it holds nowhere.
Recorded evidence blocks (14)
Q2
What did Nortriptyline's largest trial (5000 people) and its longest (20 years) measure?
5000 people in Nortriptyline's largest registered study, 20 years in its longest registered window, measuring Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality. ClinicalTrials.gov · 2026-09-01
13 phase4, 9 phase2, 7 phase3, 5 na, 3 phase1, 1 na or unstated; NCT07527481; 2027-12-31; no ageing endpoint recorded. Last human test completed 2024, NCT05531591.
Interpretation These counts include studies where Nortriptyline 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
phase4
13
phase2
9
phase3
7
na
5
phase1
3
na or unstated
1
1 more recorded row
Last recorded human testNCT05531591
2024-07-31
recorded 2026-09-01 · last checked 2026-09-04
Q3
From mouse to human: where has Nortriptyline shown lifespan?
Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality. — the recorded outcome words.
Show the evidence
mouse
lifespan
humanNCT07527481
lifespan; Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality.; 38
recorded 2026-09-01 · last checked 2026-09-04
Q4
5 of Nortriptyline's trials stopped: accrual/recruitment, other?
"Not enough participants - only 5 since the study started"; 5 of 38 registered studies
Show the evidence
Trial
NCT00547703
terminated; "Not enough participants - only 5 since the study started"
NCT00660062
terminated; "Slow inclusion"
NCT02169830
terminated; "Lack of enrollment"
NCT03652571
terminated; "The inclusion of participants went more difficult than initially thought. Preliminary analysis showed that the difference between the groups was great enough to draw conclusions from it, so the trial is terminated prematurely."
NCT04226365
terminated; "The study was stopped prematurely due to a low enrollment rate."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Nortriptyline used Nortriptyline 25mg — over how long?
1 recorded entry; human; also "Nortriptyline 25mg"
Show the evidence
humanNCT03652870
Nortriptyline 25mg
recorded 2026-09-01 · last checked 2026-09-04
Q6
More Nortriptyline was worse in human: at what point?
U-shaped in human: "Another problem is the apparent linear dose-response relationship of imipramine hydrochloride and its sister compound desipramine hydrochloride while amitriptyline and nortriptyline follow an inverted U-shaped dose-response curve." Europe PMC · dose-response search · 2004-11-01
5 recorded sentences naming Nortriptyline; U-shaped, dose-response, biphasic
Show the evidence
U-shapedPMID 390888
"Another problem is the apparent linear dose-response relationship of imipramine hydrochloride and its sister compound desipramine hydrochloride while amitriptyline and nortriptyline follow an inverted U-shaped dose-response curve."
dose-responsePMID 15494190
"The spinal anesthetic effect of nine TCAs (amitriptyline, doxepin, imipramine, trimipramine, clomipramine, protriptyline, desipramine, nortriptyline, and amoxapine) and three traditional local anesthetics (bupivacaine, lidocaine, and mepivacaine) was evaluated in rats and so were dose-response studies of amitriptyline, bupivacaine, and lidocaine."
"Imipramine and nortriptyline also caused a rightward shift in the dose-response curve of histamine-induced cAMP generation."
PMID 5768131
"Increasing doses of nortriptyline produced a parallel shift of the hypothermic log dose-response curve for intraventricular injections of noradnamine to the right.5 The minimal effective dose of nortriptyline required to reverse noradnamine hypothermia was the same whether the nortriptyline was injected directly into the lateral ventricle or subcutaneously.6."
recorded 2004-11-01 · last checked 2026-09-04
Q7
Which of 25 improvement in the ham d, assessment of frequency and severity of adverse events and average pain did Nortriptyline's trials measure?
25 improvement in the ham d, assessment of frequency and severity of adverse events and average pain lead 17 outcome terms across Nortriptyline's trials. ClinicalTrials.gov · 2026-09-01
hamilton depression rating scale, time of retention, hamilton depression scale continuous, swiss spinal stenosis questionnaire, 25 improvement in the ham d and assessment of frequency and severity of adverse events follow.
Show the evidence
hamilton rating scale for depression range
1
hamilton depression scale
1
average pain
1
hamilton depression rating scale
1
time of retention
1
hamilton depression scale continuous
1
11 more recorded rows
swiss spinal stenosis questionnaire
1
25 improvement in the ham d
1
assessment of frequency and severity of adverse events
1
response to treatment
1
quality of life instrument scores
1
psychological well being
1
serious adverse events
1
symptom response
1
depressive symptoms
1
tinnitus functional index
1
chronic post surgical pain
1
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which of Nortriptyline's 4 ongoing trials reports first?
Tinnitus Functional Index; Proportion of Patients With Chronic Post-Surgical Pain; latest 2031-07
Show the evidence
Trial
NCT06799169
"Management of Acute Tinnitus With Migraine Medications"; n 100; "Tinnitus Functional Index"; 2026-12
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
NCT07527481
"Nortriptyline and the Risk of Serious Adverse Events"; n 5000; "Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality."; 2027-12-31
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
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which running trial of Nortriptyline could settle lifespan?
NCT07527481 measures Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality., reading out 2027-12-31.
1 open trial; n 5000; "Nortriptyline and the Risk of Serious Adverse Events"
Show the evidence
TrialNCT07527481
"Nortriptyline and the Risk of Serious Adverse Events"; n 5000; "Number of participants with a 30-day composite outcome of all-cause emergency department visit, all-cause hospitalization, or all-cause mortality."; 2027-12-31
Q10
Which 13 trials of Nortriptyline posted no result?
Posted no result
13 of 13 completed trials
Registrations
NCT00000377, NCT00018148, NCT00021528, NCT00045916, NCT00009672 and NCT00544687, and 7 more
Completion dates
oldest 2000-04; newest 2024-07-31
Show the evidence
Trial
NCT00000377
2000-04
NCT00018148
2003-01
NCT00021528
2006-09
NCT00045916
2006-12
NCT00009672
2006-12-12
NCT00544687
2007-11
7 further recorded trials
NCT00557739
2008-01
NCT00721331
2008-09
NCT00796211
2009-01
NCT01065649
2010-06
NCT02881125
2019-11-30
NCT03652870
2023-04-30
NCT05531591
2024-07-31
Q11
At the median, Nortriptyline's trials enrolled 91.5 people — anything larger?
Median enrolment
91.5
Largest enrolment
5000
Registered trials counted
36
Q12
What do 881 spontaneous reports say about Nortriptyline — 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.
Nortriptyline appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 881 reaction mentions were counted: somnolence 135; coma 121; gastrooesophageal reflux disease 120; pneumonia aspiration 118. open-targets-adr · CHEMBL1201156 · 2026-06-24
Show the evidence
somnolence
135
coma
121
gastrooesophageal reflux disease
120
pneumonia aspiration
118
drug hypersensitivity
106
suicidal ideation
66
4 more recorded rows
pain
60
fatigue
57
hypersensitivity
53
constipation
45
recorded 2026-06-24 · last checked 2026-09-04
Q13
Nortriptyline and cytochrome P450: shared by which compounds?
cytochrome P450 appear in Nortriptyline's recorded interaction sentences, 3 in all. openfda-label+europepmc · 2026-08-18
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 2026-08-18 · last checked 2026-09-04
Q14
Was Nortriptyline studied with exercise?
exercise is named in Nortriptyline's label sentences: "Three participants withdrew from the trial due to adverse events related to the tested antidepressant (dry mouth, sedation, orthostatic hypotension).Secondary outcomesThe overall results post-treatment indicated that nortriptyline was not effective in improving the quality of life of individuals…" openfda-label+europepmc · 2026-08-18
1 recorded statement; exercise
Show the evidence
exercise
Three participants withdrew from the trial due to adverse events related to the tested antidepressant (dry mouth, sedation, orthostatic hypotension).Secondary outcomesThe overall results post-treatment indicated that nortriptyline was not effective in improving the quality of life of individuals with COPD, as measured by the Sickness Impact Profile (MD -2.80, 95% CI -11.02 to 5.42; P = 0.50; very…
recorded 2026-08-18 · last checked 2026-09-04
Q15
What is recorded about Nortriptyline and autophagy?
"As such, imipramine, maprotiline, fluoxetine and escitalopram were shown to induce autophagy, whereas nortriptyline, clomipramine and paroxetine were identified as autophagy inhibitors." — where Nortriptyline and autophagy appear together. Europe PMC · pathway abstract search · 2022-03-04
autophagy; PMID 35179776
Show the evidence
autophagyPMID 35179776
"As such, imipramine, maprotiline, fluoxetine and escitalopram were shown to induce autophagy, whereas nortriptyline, clomipramine and paroxetine were identified as autophagy inhibitors."
recorded 2022-03-04 · 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
✗ required summary fields resolved: 5 required field(s) not terminal: Why people use it, Best-supported result, Most important common problem, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 10 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.