This page shows what was measured, who it was measured in, and what that does not settle.
What Duloxetine does in the body
Duloxetine blocks the pumps that recycle both serotonin and noradrenaline.
Those two transmitters carry the signals in the pathways running down the spinal cord that turn pain volume down, which is why one drug is licensed for both mood and pain. The prescribing information says the exact mechanisms of the antidepressant, pain-inhibiting and anti-anxiety effects in humans are unknown, and that they are believed to be related to potentiating those two systems.
Why people take it. Depression, generalised anxiety, nerve pain from diabetes, fibromyalgia and long-term back or joint pain
What happened in people
Statistically significant reduction in 24-hour average pain and in the proportion reaching 50% pain relief in 791 patients with diabetic peripheral neuropathic pain
✎ 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.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
The limit that matters most
That a single dual-transporter mechanism explains benefit across depression, anxiety, neuropathic pain, fibromyalgia and musculoskeletal pain — stated on the label as a belief, with the mechanisms called unknown
Where it acts
Serotonin and noradrenaline transporters in the brain and in the descending pain-inhibiting pathways of the spinal cord
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 C18H19NOS∙HCl, weighing 333.88.
US prescribing information · 00628e5e-4c5b-2573-e063-6294a90a0e3b · read 2026-09-12
16 registered substances share the start of this name, which is why a search for it can return more than one thing.
FDA substance registry · 7AKC5EXT4Q · read 2026-08-29
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 109 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.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
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.
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 40 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 reviewer11 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 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.
Focus
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
…Waiting for a reviewer3 registered performance measure of this kind.
∅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.
Which registered measures put each goal on this table
Mood
recurrence of major depression; hamilton depression scale; hamilton anxiety rating scale total; 17 item hamilton depression rating scale; madrs total after 8 weeks of treatment; 17 item hamilton rating scale for depression; 24 item hamilton depression scale total at week 8; hamilton anxiety scale total at week 8
Pain
pain; visual analog scale for pain; numeric pain rating scale; clinical pain
Focus
global cognitive performance; cognitive instrumental activities of daily living; cognitive function
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
11 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.
Change from baseline in 17-item Hamilton Depression Rating Scale total score over 8 to 9 weeks in adult outpatients aged 18 to 83
✓ The study showed what it set out to show
Who was studied
Studies MDD-1 to MDD-4 (NDA 021427, section 14.2, Table 8)
Placebo-subtracted least-squares mean HAMD-17 change of −4.9 (95% CI −6.8 to −2.9) in MDD-1, −2.2 (−4.0 to −0.3) in MDD-2, −2.4 and −3.6 in MDD-3, and −2.2 and −3.3 in MDD-4; all dose groups statistically superior to placebo
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. Four of the six dose arms produced a difference below three points on a scale whose baseline values ran 17.2 to 21.5. The label states there is no evidence that doses above 60 mg/day confer additional benefit, despite 80 and 120 mg/day arms being studied. Confidence intervals were not adjusted for multiplicity in the multi-dose trials.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Delayed-release capsules of enteric-coated pellets at 20, 30, 40 and 60 mg, taken once or twice daily; a sprinkle formulation exists for people who cannot swallow capsules
Interval reported. 95% CI −6
Written into the record, not signed off as a reviewed claim.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
Change in 24-hour average pain severity on an 11-point diary scale in adults with diabetic peripheral neuropathic pain of at least six months’ duration
✓ The study showed what it set out to show
Who was studied
Studies DPNP-1 and DPNP-2 (NDA 021427, section 14.4)
60 mg once or twice daily statistically significantly improved endpoint mean pain scores and increased the proportion of patients achieving at least a 50% reduction from baseline
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. 592 of 791 patients (75%) completed. Patients could take up to 4 g of paracetamol daily alongside the study drug. Non-completers were assigned 0% improvement in the responder figures. The glycaemic effect that these same trials produced appeared in the extension phase, not in these 12 weeks.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Delayed-release capsules of enteric-coated pellets at 20, 30, 40 and 60 mg, taken once or twice daily; a sprinkle formulation exists for people who cannot swallow capsules
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
Section 14 states these trials did not demonstrate efficacy; the label summarises them alongside the positive trials rather than omitting them
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. The label does not state randomised sample sizes for these three studies in the section text, so none is asserted here. A one-in-three failure rate disclosed on the label is better practice than the field norm the Turner analysis measured, in which 22 of the FDA’s negative antidepressant trials were never published at all.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Delayed-release capsules of enteric-coated pellets at 20, 30, 40 and 60 mg, taken once or twice daily; a sprinkle formulation exists for people who cannot swallow capsules
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
Percentage change in weekly incontinence episodes and change in Incontinence Quality of Life total score in women with stress urinary incontinence
✓ The study showed what it set out to show
Who was studied
Four European stress urinary incontinence trials, reanalysed from clinical study reports (CMAJ 2017;189:E194-E203)
How many people
1913
Study design
Meta-analysis of four randomised, double-blind, placebo-controlled trials
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Mean difference −13.56% (95% CI −21.59 to −5.53) in weekly incontinence episodes and 3.24 (2.00 to 4.48) on Incontinence Quality of Life; number needed to treat 8 (6 to 13) for a global impression of much or very much better
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. Number needed to harm 7 (95% CI 6 to 8) for discontinuation due to an adverse event and 7 (6 to 9) for an activation event. The authors concluded harms outweighed benefits. The analysis used 6,870 pages of clinical study reports including individual patient data obtained from the European Medicines Agency. There is no United States indication for this use.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Delayed-release capsules of enteric-coated pellets at 20, 30, 40 and 60 mg, taken once or twice daily; a sprinkle formulation exists for people who cannot swallow capsules
Interval reported. 95% CI −21
Written into the record, not signed off as a reviewed claim.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
RNAWiki holds 4 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 eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.1 registered measure of this kind. No reviewed result.
■What a body can do day to dayEvidence recorded. Walking, dressing, breathing, recovering.3 registered measures of this kind.
■Measured performanceEvidence recorded. How much was lifted, how far was run, how fast.3 registered measures of this kind.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.17 registered measures of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.2 registered measures of this kind.
■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.
Where a source records it acting
Brain: Actions believed to be related to potentiation of serotonergic and noradrenergic activity in the CNS (as recorded)
US prescribing information · 05a744a5-64ef-42d7-a19c-568be5a272d4 · read 2026-08-27
Start
Duloxetine
What a person takes: Delayed-release capsules of enteric-coated pellets at 20, 30, 40 and 60 mg, taken once or twice daily; a sprinkle formulation exists for people who cannot swallow capsules.
The measurement behind this step
The molecule is acid-labile, so the pellets carry an enteric coat that delays release until the small intestine. Metabolism involves CYP1A2 and CYP2D6. Plasma concentrations of duloxetine and especially its metabolites rise in end-stage renal disease, and the drug is not recommended below a glomerular filtration rate of 30 mL/minute. The dosage form is the reason dose steps are limited to the marketed strengths.
Getting in
A capsule of coated beads, because the molecule dissolves in acid
Duloxetine breaks down in stomach acid, so it is packed as tiny coated pellets that survive the stomach and release in the intestine. That is also why the capsule cannot be split.
╌╌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 naphthyl ether is acid-labile, so the product is a delayed-release capsule of enteric-coated spheroids rather than a tablet. Generic entry required matching a two-stage dissolution profile, not only the molecule, and the formulation constrains the available dose steps to the marketed strengths.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
Reaching the cell
Cleared by two enzymes, one of them easily blocked
The liver removes it using two different enzymes. One of them, CYP1A2, is blocked by several common drugs, which is why some combinations are ruled out entirely.
──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
Metabolism involves CYP1A2 and CYP2D6. The label directs avoiding co-administration with CYP1A2 inhibitors and with thioridazine. Increased plasma concentrations of duloxetine, and especially of its metabolites, occur in end-stage renal disease, and use is not recommended below a glomerular filtration rate of 30 mL/minute.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
What it acts on
Both monoamine pumps are blocked
Serotonin and noradrenaline are both left in the gap between nerve cells for longer. Unlike venlafaxine, duloxetine does this across its whole usual dose range rather than only at the top.
╌╌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
Potent inhibition of both SLC6A4 and SLC6A2. The label states the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions in humans are unknown and are believed to relate to potentiation of serotonergic and noradrenergic activity in the central nervous system. It also records that there is no evidence doses above 60 mg/day confer additional benefit in depression.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
The change it makes
The descending pain pathway turns its volume down
Nerves running from the brain down the spinal cord dampen incoming pain signals, and they use these same two transmitters. This is the most concrete of the drug’s three proposed actions.
──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 descending inhibitory pathways from the periaqueductal grey and rostral ventromedial medulla to the dorsal horn are serotonergic and noradrenergic, which is the pharmacological rationale for licensing an antidepressant in neuropathic and musculoskeletal pain. Efficacy in diabetic peripheral neuropathic pain rests on two 12-week fixed-dose trials in 791 patients, with some reduction in pain from week 1.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
What that does for a person
Scores fall, in most trials
Depression scores fell about two to five points more than placebo. Three pain trials named on the label did not show a benefit at all.
╌╌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
Placebo-subtracted HAMD-17 differences of 2.2 to 4.9 points across four fixed-dose depression trials. In diabetic neuropathic pain, 60 mg once or twice daily significantly improved endpoint mean pain scores and the proportion achieving at least 50% pain reduction. Studies FM-3, CLBP-2 and OA-2 did not demonstrate efficacy and are named on the label.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
What that does for a person
And two laboratory values move the wrong way
Liver enzymes rise in about one in eighty people, and in diabetic patients blood sugar drifts upward over a year. Neither is something a person feels.
╌╌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
ALT above three times the upper limit of normal in 1.25% against 0.45% on placebo, with a median two months to detection and a dose-response relationship. In the diabetic neuropathy extension to 52 weeks, mean fasting glucose rose 12 mg/dL on duloxetine and fell 11.5 mg/dL on routine care, with HbA1c rising 0.5% against 0.2%.
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · 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 scale
pain
hamilton anxiety rating scale total
clinical global impression of severity
visual analog scale for pain
17 item hamilton depression rating scale
numeric pain rating scale
madrs total after 8 weeks of treatment
17 item hamilton rating scale for depression
24 item hamilton depression scale total at week 8
and 7 more.
Measured
Things only a test, a scale or a device shows.
blood level concentrations of the drugs in use
concentration of o desmethyltramadol
Meaningful
Things that change how a life goes, not only a number.
global cognitive performance
cognitive instrumental activities of daily living
probability of remission
cognitive function
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 (17)
recurrence of major depression
adverse events
panic disorder severity scale
y bocs scores at 1st and last visit
international normalized
who experienced an adverse event
time of retention
ham d 24 total after 8 weeks of treatment
cmax
tmax
t1/2
rate of enrollment
rate of retention
adverse events all
machine learning
ybocs obsessive compulsive severity
clinical global improvement improvement scale
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. about 12 hours (range 8 to 17 hours) hours
Read from the label, which states: “Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours) and its pharmacokinetics are dose proportional over the therapeutic range.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
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 across five indications; children from seven for generalized anxiety disorder and from thirteen for fibromyalgia. It is to be avoided in substantial alcohol use or evidence of chronic liver disease, and in uncontrolled narrow-angle glaucoma.
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: “The safety and effectiveness of duloxetine delayed-release capsules have not been established in pediatric patients with major depressive disorder (MDD), diabetic peripheral neuropathic pain, or chronic musculoskeletal pain.”
US prescribing information · b32a39d8-5f1a-4e44-bc46-b65925bde753 · read 2026-08-30
On older people, the label states: “Geriatric Exposure in Premarketing Clinical Trials of Duloxetine Delayed-Release Capsules Of the 2,418 patients in MDD trials, 6% (143) were 65 years of age or over.”
US prescribing information · b32a39d8-5f1a-4e44-bc46-b65925bde753 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage.”
US prescribing information · b32a39d8-5f1a-4e44-bc46-b65925bde753 · read 2026-08-30
On people who are breastfeeding, the label states: “Data Disposition of duloxetine delayed-release capsules was studied in 6 lactating women who were at least 12 weeks postpartum and had elected to wean their infants.”
US prescribing information · b32a39d8-5f1a-4e44-bc46-b65925bde753 · read 2026-08-30
On people with reduced liver function, the label states: “Patients with clinically evident hepatic impairment have decreased duloxetine metabolism and elimination.”
US prescribing information · b32a39d8-5f1a-4e44-bc46-b65925bde753 · read 2026-08-30
Where the result stopped carrying
Studies FM-3, CLBP-2 and OA-2 did not demonstrate efficacy, and the label names all three
Hepatic failure, sometimes fatal, is on the label, with transaminase elevation forcing discontinuation in 92 of 34,756 treated patients
Glycaemic control worsened over a year in the diabetic neuropathy population the drug is licensed to treat
The stress urinary incontinence indication exists in the European Union and not in the United States, and the independent analysis of the underlying study reports concluded harms outweighed benefits
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
Delayed-release capsules of enteric-coated pellets at 20, 30, 40 and 60 mg, taken once or twice daily; a sprinkle formulation exists for people who cannot swallow capsules
✎ 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
The molecule is acid-labile, so the pellets carry an enteric coat that delays release until the small intestine. Metabolism involves CYP1A2 and CYP2D6. Plasma concentrations of duloxetine and especially its metabolites rise in end-stage renal disease, and the drug is not recommended below a glomerular filtration rate of 30 mL/minute. The dosage form is the reason dose steps are limited to the marketed strengths.
✎ 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. Hepatotoxicity including fatal hepatic failure, with avoidance directed in substantial alcohol use or chronic liver disease. Orthostatic hypotension, falls and syncope. Serotonin syndrome. Increased bleeding risk with antiplatelets and anticoagulants. Severe skin reactions including erythema multiforme and Stevens-Johnson syndrome. Activation of mania or hypomania. Angle-closure glaucoma. Seizures. Blood pressure increases, with monitoring directed before and during treatment. Hyponatraemia with SIADH. Worsened glycaemic control in diabetes. Urinary hesitation and retention, sometimes requiring catheterisation. Sexual dysfunction. Discontinuation syndrome after tapered as well as abrupt stopping. Co-administration with CYP1A2 inhibitors or thioridazine is to be avoided.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Duloxetine delayed-release capsules United States prescribing information — Boxed Warning, Warnings and Precautions 5.2 Hepatotoxicity, 5.7 Discontinuation S… · a recorded source, not a stored snapshot
European Medicines Agency, Yentreve (duloxetine) European public assessment report — marketing authorisation granted 11 August 2004 for moderate to severe st… · a recorded source, not a stored snapshot
Reports sent to a regulator
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.
Duloxetine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2427 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
Delayed-release capsules of enteric-coated pellets at 20, 30, 40 and 60 mg, taken once or twice daily; a sprinkle formulation exists for people who cannot swallow capsules
✎ 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
Metabolism involves CYP1A2 and CYP2D6. Plasma concentrations of duloxetine and especially its metabolites rise in end-stage renal disease, and the drug is not recommended below a glomerular filtration rate of 30 mL/minute. The dosage form is the reason dose steps are limited to the marketed strengths.
✎ 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
241 products list this as an active ingredient in the United States drug directory. 241 of them contain it and nothing else.
FDA National Drug Code directory · 72162-1600 · read 2026-08-29
They are sold as capsule, delayed release, capsule, delayed release pellets and powder, taken oral.
FDA National Drug Code directory · 72162-1600 · read 2026-08-29
The regulator's established pharmacologic class for it is norepinephrine uptake inhibitors [moa], serotonin uptake inhibitors [moa] and serotonin and norepinephrine reuptake inhibitor [epc].
FDA National Drug Code directory · 72162-1600 · read 2026-08-29
132 published labels name it as an active ingredient. 132 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · b32a39d8-5f1a-4e44-bc46-b65925bde753 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · b32a39d8-5f1a-4e44-bc46-b65925bde753 · read 2026-08-29
Duloxetine delayed-release capsules is delayed-release capsules at Delayed-release capsules: 20 mg, 30 mg, and 60 mg, recorded as prescription product; fda label in effect 2026-04-22 in the United States.
US prescribing information · 05a744a5-64ef-42d7-a19c-568be5a272d4 · read 2026-08-27
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 Duloxetine 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 single dual-transporter mechanism explains benefit across depression, anxiety, neuropathic pain, fibromyalgia and musculoskeletal pain — stated on the label as a belief, with the mechanisms called unknown
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 a positive trial in one of the five indications supports the pharmacology in the others, which the label’s three named failed trials cut against
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 doses above 60 mg/day add benefit in depression, which the label explicitly denies
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 acute-phase glycaemic reassurance carries to long-term use, when the effect emerged only in the 52-week extension
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.
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 Duloxetine 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 depression licence is a two-to-five-point Hamilton difference
In plain words
Four fixed-dose trials supported the depression indication. The gap between drug and placebo on the 17-item Hamilton scale was 4.9 points in one, and between 2.2 and 3.6 points in the other five dose arms.
What was measured
Placebo-subtracted least-squares mean change in 17-item Hamilton score across four fixed-dose registration trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Table 8 of the label reports placebo-subtracted least-squares mean changes in HAMD-17 total score: Study MDD-1, 60 mg/day, −4.9 (95% CI −6.8 to −2.9); Study MDD-2, 60 mg/day, −2.2 (−4.0 to −0.3); Study MDD-3, 20 mg twice daily −2.4 (−4.7 to −0.2) and 40 mg twice daily −3.6 (−5.9 to −1.4); Study MDD-4, 40 mg twice daily −2.2 (−3.6 to −0.9) and 60 mg twice daily −3.3 (−4.7 to −1.9). Baseline scores ran 17.2 to 21.5. The label adds that there is no evidence doses above 60 mg/day confer additional benefit, despite two of the four trials using 80 and 120 mg/day arms. Four of the six dose arms produced a difference below three points, the threshold the United Kingdom’s NICE has used as a marker of clinical significance on this scale. All six are statistically significant and every confidence interval excludes zero; the question the numbers raise is not whether the effect is real but how large it is, and the label prints the answer.
Source
Duloxetine United States prescribing information, section 14.2 Major Depressive Disorder in Adults, Table 8 (NDA 021427)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The label names its own three failed trials by study number
In plain words
Most labels print only the trials that worked. This one lists three that did not: a sixteen-week fibromyalgia trial, a thirteen-week back pain trial and a thirteen-week osteoarthritis trial.
What was measured
Number of registration trials in fibromyalgia and chronic musculoskeletal pain that did not demonstrate efficacy, as disclosed on the label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Section 14 states: "Additionally, a summary of the following trials that did not demonstrate efficacy are presented below: Study FM-3 (a 16-week trial in adult patients with fibromyalgia), Study CLBP-2 (a 13-week trial in adult patients with CLBP), and Study OA-2 (a 13-week trial in adult patients with chronic pain due to OA)." The chronic musculoskeletal pain indication rests on two of three chronic low back pain and osteoarthritis trials, and the fibromyalgia indication on two of three adult trials. That is a one-in-three failure rate disclosed on the document itself, which is a materially better disclosure practice than the field average that the Turner analysis found — where 22 of the FDA’s negative antidepressant trials were never published at all. A label that names its failures is doing the thing this site exists to check.
Written into the record, not signed off as a reviewed claim
It worsened blood sugar in the diabetic patients it was licensed to help
In plain words
Duloxetine is licensed for the nerve pain that diabetes causes. In the year-long extension of its own diabetic neuropathy trials, average fasting glucose rose 12 mg/dL on the drug while the comparison group’s fell 11.5, and HbA1c rose more than twice as much.
What was measured
Change in mean fasting blood glucose and HbA1c over an extension phase of up to 52 weeks, drug against routine care
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Section 5.14 states that duloxetine treatment worsened glycaemic control in some patients with diabetes. Across three trials in neuropathic pain associated with diabetic peripheral neuropathy, mean diabetes duration was about 12 years, mean baseline fasting blood glucose 176 mg/dL and mean baseline HbA1c 7.8%. In the 12-week acute phase, duloxetine was associated with a small increase in mean fasting glucose against placebo. In the extension phase, lasting up to 52 weeks, mean fasting blood glucose increased by 12 mg/dL on duloxetine and decreased by 11.5 mg/dL in the routine care group, and HbA1c increased 0.5% against 0.2%. Two caveats belong with the finding: the comparator in the extension was routine care rather than a randomised placebo, and the acute-phase effect was described as small. The structure of the problem stands regardless — the effect emerges over a year in a population whose complication burden depends on exactly that measurement, and the acute trials were far too short to see it.
Source
Duloxetine United States prescribing information, section 5.14 Glycemic Control in Patients with Diabetes (NDA 021427)
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
Liver injury, sometimes fatal, at nearly three times the placebo rate
In plain words
Alanine transaminase rose above three times the upper limit of normal in 1.25% of people on duloxetine against 0.45% on placebo, and the label records reports of hepatic failure, sometimes fatal.
What was measured
Proportion with ALT above three times the upper limit of normal, drug against placebo, and discontinuations for transaminase elevation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Section 5.2 records hepatic failure, sometimes fatal, presenting as hepatitis with abdominal pain, hepatomegaly and transaminase elevation above twenty times the upper limit of normal with or without jaundice, in a mixed or hepatocellular pattern; cases of cholestatic jaundice with minimal transaminase elevation have also been reported. Transaminase elevations led to discontinuation in 0.3% of treated patients (92 of 34,756). In adult placebo-controlled trials, ALT above three times the upper limit of normal occurred in 1.25% (144 of 11,496) on duloxetine against 0.45% (39 of 8,716) on placebo, with a dose-response relationship in the fixed-dose studies for both ALT above three times and AST above five times normal. Median time to detection was about two months. The label directs avoiding the drug in substantial alcohol use or evidence of chronic liver disease and discontinuing it on jaundice or clinically significant liver dysfunction, not to be resumed unless another cause is established.
Source
Duloxetine United States prescribing information, section 5.2 Hepatotoxicity (NDA 021427)
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
Licensed for incontinence in Europe; the study reports showed harms outweighing benefits
In plain words
Duloxetine is authorised in the European Union for stress urinary incontinence in women and carries no such indication in the United States. When independent researchers obtained the full clinical study reports, eight women had to be treated for one to feel much better and seven for one to stop because of a side effect.
What was measured
Number needed to treat for global improvement against numbers needed to harm for discontinuation and activation, from clinical study reports
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Yentreve, duloxetine 20 and 40 mg, received European Commission marketing authorisation on 11 August 2004 for moderate to severe stress urinary incontinence in women and remains authorised; the United States label carries no such indication. In 2017 a Nordic Cochrane Centre team obtained the clinical study reports for the four randomised placebo-controlled trials submitted to the European Medicines Agency — 1,913 patients across 6,870 pages including individual patient data — and meta-analysed benefits and harms. Duloxetine was significantly better than placebo on percentage change in weekly incontinence episodes (mean difference −13.56%, 95% CI −21.59 to −5.53) and on Incontinence Quality of Life total score (mean difference 3.24, 95% CI 2.00 to 4.48), but the effect sizes were small: in a sensitivity analysis the number needed to treat for a patient global impression of "much better or very much better" was 8 (95% CI 6 to 13), against numbers needed to harm of 7 (6 to 8) for discontinuing because of an adverse event and 7 (6 to 9) for an activation event. No suicidality, violence or akathisia events were noted. The authors concluded the harms outweighed the benefits. Two regulators looking at overlapping data reached different conclusions about the same indication, and the full study reports were the thing that made the disagreement examinable.
Written into the record, not signed off as a reviewed claim
A dosage form that makes coming off it harder
In plain words
The capsule holds enteric-coated pellets rather than a solid tablet, so it cannot be split to make a smaller dose. That matters because the label documents a discontinuation syndrome and directs gradual reduction.
What was measured
Discontinuation-emergent adverse reactions after tapered as well as abrupt stopping, and comparative dropout ranking
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Discontinuation symptoms were systematically evaluated. Following abrupt or tapered discontinuation in adult placebo-controlled trials, dizziness, headache, nausea, diarrhoea, paraesthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis and fatigue each occurred at 1% or greater and significantly more often than on placebo — notably, after tapered as well as abrupt stopping. Postmarketing reports across the SSRI and SNRI classes add dysphoric mood, agitation, electric-shock sensory disturbances, confusion, lethargy, emotional lability, hypomania, tinnitus and seizures, some severe. The label directs gradual dose reduction rather than abrupt cessation whenever possible. The drug is acid-labile, so it is formulated as enteric-coated pellets in a capsule; that formulation is why the available step sizes are the marketed strengths and nothing between them. In the 2018 network meta-analysis duloxetine sat among the antidepressants with the highest dropout rates (range of odds ratios 1.30 to 2.32).
Written into the record, not signed off as a reviewed claim
One pharmacology offered for five different conditions, mechanism unknown
In plain words
Depression, generalised anxiety, diabetic nerve pain, fibromyalgia and chronic musculoskeletal pain are all attributed to the same two-transmitter action. The label says the exact mechanisms are unknown.
What was measured
That one dual-transporter mechanism explains benefit across five unrelated conditions — a belief the label states as such and that its own failed trials in three of those conditions complicate
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 12.1 reads: "Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS." The descending inhibitory pain pathway does use both transmitters, which makes the pain rationale more concrete than the mood one — but the label states all three as beliefs rather than findings. The 2022 umbrella review of the serotonin theory found no consistent evidence of a serotonergic abnormality in depression, and no comparable body of evidence establishes a noradrenergic one. The commercial consequence of a single presumed mechanism spanning five indications is that a positive trial in one condition is routinely read as support for the pharmacology in all five, which is exactly the inference the label’s three named failed trials should discourage.
This order is fixed in code and does not count clicks or time on the page.
What is not here
3 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.
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.
A dual serotonin-noradrenaline reuptake inhibitor whose depression licence rests on placebo-subtracted 17-item Hamilton differences of 2.2 to 4.9 points across four fixed-dose trials, whose label names three further trials in fibromyalgia, back pain and osteoarthritis that did not demonstrate efficacy, and which raised mean fasting glucose by 12 mg/dL over 52 weeks in the diabetic neuropathy population it is licensed to treat.
Recorded evidence blocks (14)
Q2
What did Duloxetine's largest trial (3255526 people) and its longest (19 years) measure?
3255526 people in Duloxetine's largest registered study, 19 years in its longest registered window, measuring Hamilton Depression Rating Scale: Stratified by Baseline Frailty. ClinicalTrials.gov · 2026-09-01
107 phase3, 105 phase4, 55 na, 51 phase2, 17 na or unstated, 16 phase1, 5 early phase1; NCT07531173; 2027-12-31. Last human test completed 2026, NCT06711978.
Interpretation These counts include studies where Duloxetine 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
phase3
107
phase4
105
na
55
phase2
51
na or unstated
17
phase1
16
2 more recorded rows
early phase1
5
Last recorded human testNCT06711978
2026-04-15
recorded 2026-09-01 · last checked 2026-09-04
Q3
From mouse to human: where has Duloxetine shown healthspan?
Duloxetine's half-life is about 12 hours (range 8 to 17 hours) — which schedules were studied?
about 12 hours (range 8 to 17 hours), the half-life Duloxetine's label states. openfda-label · 00628e5e-4c5b-2573-e063-6294a90a0e3b · 2026-08-27
Show the evidence
half life
about 12 hours (range 8 to 17 hours) hours; Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours) and its pharmacokinetics are dose proportional over the therapeutic range.
metabolism
Elimination of duloxetine is mainly through hepatic metabolism involving two P450 isozymes, CYP1A2 and CYP2D6.
recorded 2026-08-27 · last checked 2026-09-04
Q7
Which of 17 item hamilton depression rating scale, 17 item hamilton rating scale for depression and 24 item hamilton depression scale total at week 8 did Duloxetine's trials measure?
17 item hamilton depression rating scale, 17 item hamilton rating scale for depression and 24 item hamilton depression scale total at week 8 lead 40 outcome terms across Duloxetine's trials. ClinicalTrials.gov · 2026-09-01
adverse events, hamilton depression scale, pain, panic disorder severity scale, y bocs scores at 1st and last visit and hamilton anxiety rating scale total follow.
Show the evidence
global cognitive performance
1
cognitive instrumental activities of daily living
1
recurrence of major depression
1
adverse events
1
hamilton depression scale
1
pain
1
14 more recorded rows
panic disorder severity scale
1
y bocs scores at 1st and last visit
1
hamilton anxiety rating scale total
1
clinical global impression of severity
1
visual analog scale for pain
1
17 item hamilton depression rating scale
1
international normalized
1
numeric pain rating scale
1
madrs total after 8 weeks of treatment
1
who experienced an adverse event
1
17 item hamilton rating scale for depression
1
probability of remission
1
24 item hamilton depression scale total at week 8
1
hamilton anxiety scale total at week 8
1
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which of Duloxetine's 33 ongoing trials reports first?
"Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants"; n 1600; "M/P ratio"; 2028-07-31
NCT04137107
"Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neuropathy in Patients With Stage II-III Colorectal Cancer"; n 220; "Prevention of sensory oxaliplatin-induced peripheral neuropathy (OIPN) response (Phase II)"; 2026-12-31
NCT04560673
"Duloxetine and Neurofeedback Training for the Treatment of Chemotherapy Induced Peripheral Neuropathy"; n 336; "Change in Pain Quality Assessment Scale (PQAS) unpleasantness score"; 2026-12-31
NCT04970121
"Efficacy and Safety of Duloxetine in Chinese Solid Tumor Patients with Taxanes-induced Painful Peripheral Neuropathy"; n 100; "Pain Score"; 2025-12-01
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
14 further recorded trials
NCT05786599
"Methadone to Treat Painful Chemotherapy Induced Peripheral Neuropathy"; n 50; "Efficacy of methadone compared to duloxetine to reduce the reported average pain intensity using the Brief Pain Inventory-Short Form questionnaire."; 2026-03
NCT05814640
"Sequenced Treatment Alternatives to Relieve Adolescent Depression (STAR-AD)"; n 520; "Change in CDRS-R (Children's Depression Rating Scale) scores from baseline"; 2027-07-01
NCT05840562
"Capsaicin 179 mg Patch Versus Oral Duloxetine in Patients With Chemotherapy-induced Peripheral Neuropathy"; n 274; "The primary objective is to demonstrate that capsaicin 179 mg patch once compared to duloxetine daily, improves painful CIPN after a 5-week treatment period."; 2028-03
NCT05851898
"Serotonin-norepinephrine Reuptake Inhibitor in Prophylaxis of Depression Following Fragility Fractures"; n 100; "Geriatric Depression Scale (Short Form) Scores"; 2028-12
NCT05851976
"Duloxetine for LBP"; n 120; "Number of participants with moderate or severe Low Back Pain (LBP)"; 2027-05
NCT05949229
"The Effect of Preoperative Duloxetine on the Occurance of Postoperative Delirium in Patients Undergoing Cancer Surgery."; n 42; "postoperative delirium"; 2026-12
NCT05976347
"Identifying and Treating Depression in the Orthopaedic Trauma Population"; n 100; "Depressive Symptom Scores"; 2027-05
NCT06232473
"Patient Education and Duloxetine, Alone and in Combination, for Patients With Multisystem Functional Somatic Disorder"; n 424; "Mean difference between groups in Short-Form Health Survey (SF-36) aggregate score"; 2029-11-01
NCT06245109
"Brain-Based and Clinical Phenotyping of Pain Pharmacotherapy in Knee Osteoarthritis"; n 180; "Percentage of Individuals with at least 30% Pain Response to treatment"; 2028-03-15
NCT06407401
"Improvement of Quality of Life Through Supportive Treatments for Hormone Therapy - Related Symptoms in Patients With Early Breast Cancer"; n 399; "Endocrine therapy related musculoskeletal pain"; 2028-11-30
NCT06423716
"Effect of peRiopErative duLoxetIne Administration on Opioid Consumption Following Total kneE Arthroplasty (RELIFE)"; n 150; "Opioid consumption"; 2027-12-31
NCT06551051
"ADC-induced Neurotoxicity Treated With Duloxetine"; n 37; "Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale"; 2025-12-30
NCT06606067
"Duloxetine to Prevent Chronic Postsurgical Pain After Inguinal Hernia Repair in Patients at High Risk"; n 294; "Efficacy of duloxetine versus placebo in reducing the incidence of Chronic Post-Surgical Pain (CPSP) at 4 months"; 2026-12-31
NCT06614322
"SPENDD: Quantitative Sensory Testing and Analgesic Response for Painful Peripheral Neuropathy."; n 190; "Pain Intensity"; 2028-06
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which running trial of Duloxetine could settle lifespan?
NCT07531173 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 8688; "Serotonin Norepinephrine Reuptake Inhibitors and the Risk of Serious Adverse Events"
Show the evidence
TrialNCT07531173
"Serotonin Norepinephrine Reuptake Inhibitors and the Risk of Serious Adverse Events"; n 8688; "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 113 trials of Duloxetine posted no result?
Posted no result
113 of 113 completed trials
Registrations
NCT00042575, NCT00036335, NCT00036309, NCT00042562, NCT00489073 and NCT00067912, and 107 more
Completion dates
oldest 2002-08; newest 2024-04-08
Show the evidence
Trial
NCT00042575
2002-08
NCT00036335
2003-01
NCT00036309
2003-07
NCT00042562
2003-12
NCT00489073
2003-12
NCT00067912
2004-03
14 further recorded trials
NCT00071695
2004-05
NCT00062673
2004-07
NCT00475397
2004-10
NCT00479726
2005-01
NCT00475358
2005-02
NCT00058968
2005-03
NCT00475696
2005-03
NCT00073411
2005-05
NCT00475969
2005-06
NCT00489775
2005-06
NCT00494377
2005-06
NCT00190905
2005-07
NCT00122824
2005-09
NCT00191685
2005-09
Q11
At the median, Duloxetine's trials enrolled 120 people — anything larger?
Median enrolment
120
Largest enrolment
3255526
Registered trials counted
343
Q12
What do 2427 spontaneous reports say about Duloxetine — 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.
Duloxetine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2427 reaction mentions were counted: serotonin syndrome 369; somnolence 343; drug interaction 284; drug hypersensitivity 249. open-targets-adr · CHEMBL1175 · 2026-06-24
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serotonin syndrome
369
somnolence
343
drug interaction
284
drug hypersensitivity
249
coma
239
anxiety
210
4 more recorded rows
confusional state
205
hyponatraemia
180
pneumonia aspiration
175
gastrooesophageal reflux disease
173
recorded 2026-06-24 · last checked 2026-09-04
Q13
Duloxetine and CYP1A2 and CYP2D6: shared by which compounds?
CYP1A2 and CYP2D6 appear in Duloxetine's recorded interaction sentences, 4 in all. openfda-label+europepmc · 2026-08-30
Interpretation pharmacokinetics
Show the evidence
CYP1A2
pharmacokinetics
Elimination of duloxetine is mainly through hepatic metabolism involving two P450 isozymes, CYP1A2 and CYP2D6.
pharmacokinetics
Both CYP1A2 and CYP2D6 catalyze the oxidation of the naphthyl ring in vitro .
CYP2D6
pharmacokinetics
Elimination of duloxetine is mainly through hepatic metabolism involving two P450 isozymes, CYP1A2 and CYP2D6.
pharmacokinetics
Both CYP1A2 and CYP2D6 catalyze the oxidation of the naphthyl ring in vitro .
recorded 2026-08-30 · last checked 2026-09-04
Q14
Was Duloxetine studied with exercise?
exercise is named in Duloxetine's label sentences: "Four interventions were chosen for the trial: Enhanced Self-Care, Acceptance and Commitment Therapy, Duloxetine, and Evidence-Based Exercise and Manual Therapy." openfda-label+europepmc · 2026-08-30
1 recorded statement; exercise
Show the evidence
exercise
Four interventions were chosen for the trial: Enhanced Self-Care, Acceptance and Commitment Therapy, Duloxetine, and Evidence-Based Exercise and Manual Therapy.
recorded 2026-08-30 · last checked 2026-09-04
Q15
What is recorded about Duloxetine and autophagy?
"Selected compounds underwent further <i>in vitro</i> validation, leading to the identification of duloxetine, a Food and Drug Administration (FDA)-approved drug, as an effective autophagy inhibitor at low-micromolar concentrations." — where Duloxetine and autophagy appear together. Europe PMC · pathway abstract search · 2026-03-16
"Selected compounds underwent further <i>in vitro</i> validation, leading to the identification of duloxetine, a Food and Drug Administration (FDA)-approved drug, as an effective autophagy inhibitor at low-micromolar concentrations."
AMPKPMID 41787744
"Altogether, our findings suggest that early autophagy inhibition is neuroprotective in stroke, and duloxetine serves as an effective means of achieving this inhibition.<b>Abbreviation:</b> AMPK - AMP-activated protein kinase; ATG5 - autophagy related 5; AVs - autophagic vacuoles; Baf -bafilomycin A<sub>1</sub>; BBB - blood-brain barrier; BECN1 -beclin 1; CAMK2 -calcium/calmodulin dependent…"
autophagyPMID 41787744
"Altogether, our findings suggest that early autophagy inhibition is neuroprotective in stroke, and duloxetine serves as an effective means of achieving this inhibition.<b>Abbreviation:</b> AMPK - AMP-activated protein kinase; ATG5 - autophagy related 5; AVs - autophagic vacuoles; Baf -bafilomycin A<sub>1</sub>; BBB - blood-brain barrier; BECN1 -beclin 1; CAMK2 -calcium/calmodulin dependent…"
mTORPMID 40694169
"Moreover, duloxetine significantly inhibited the phosphorylation of AKT and mTOR, thereby promoting autophagy activation, as evidenced by increased LC3 expression and decreased P62 levels."
autophagyPMID 40694169
"Moreover, duloxetine significantly inhibited the phosphorylation of AKT and mTOR, thereby promoting autophagy activation, as evidenced by increased LC3 expression and decreased P62 levels."
mTOR
PMID 40694169
"These findings reveal that duloxetine exerts anti-breast cancer effects through inhibiting AKT/mTOR signaling and promoting Bax/Bcl-2-mediated apoptosis, highlighting its potential for therapeutic repurposing as an adjunct treatment-particularly, in breast cancer patients with coexisting depression."
"We propose a fully oral, low-cost, four-component regimen designed to replicate ketamine's entire plasticity cascade: (1) dextromethorphan (DXM) supplies fast NMDA antagonism; (2) a strong CYP2D6 inhibitor (fluoxetine, paroxetine, or high-dose duloxetine) prolongs DXM exposure without relying on bupropion; (3) the AMPA positive allosteric modulator piracetam amplifies the downstream glutamate…"
AMPK
PMID 31810927
"Treatment with duloxetine inhibited AMPK phosphorylation and resulted in increased p62 and microtubule-associated protein 1A/1B light chain 3B-II levels, indicating inhibition of autophagy flux."
PMID 34043989
"In suppressing LC progression, anti-tumor compounds including metformin, ginsenosides, casticin and duloxetine dually induce/inhibit AMPK signaling."
NAD+
PMID 9375697
"Duloxetine (5.0 mg/kg, s.c.), a mixed inhibitor of 5-HT and NAD reuptake, and fluoxetine (10.0 mg/kg, s.c.), a selective 5-HT reuptake inhibitor, both increased levels of 5-HT (by 150 and 120%, respectively), NAD (by 400 and 100%, respectively), and DA (by 115 and 55%, respectively)."
PMID 10432475
"(-)-Pindolol potentiated the increase in FCX levels of 5-HT elicited by the 5-HT reuptake inhibitors, fluoxetine and duloxetine, and also enhanced their ability to elevate FCX levels of DA--though not of NAD."
recorded 2026-03-16 · last checked 2026-09-04
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