This page shows what was measured, who it was measured in, and what that does not settle.
What Thioridazine does in the body
The effect grows with dose, with blood level, and with how slowly a person's liver clears the drug.
Thioridazine treats psychosis by blocking dopamine receptors. It also blocks a potassium channel that heart muscle cells use to reset their electrical charge after each beat. With that channel blocked, resetting takes longer, the QT interval on an electrocardiogram lengthens, and the heart becomes vulnerable to a chaotic rhythm called torsades de pointes that can stop it.
Why people take it. Formerly used as an antipsychotic and now largely withdrawn.
What happened in people
It was one of the strongest predictors of a dangerously prolonged heart reading among 495 psychiatric patients.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
The abnormal reading predicts risk but is not itself a dangerous rhythm.
Where it acts
Mesolimbic dopamine pathways; the toxicity site is the ventricular myocyte repolarising current
Kind of result
The kind of result is not recorded
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
The substance registry classes this as chemical.
FDA substance registry · N3D6TG58NI · 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.
A reviewer approved this sentence against this exact record and its sources.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 101 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.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
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.
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.
Point prevalence of QTc lengthening above 456 ms and its predictors among psychiatric inpatients and community patients
✓ The study showed what it set out to show
Who was studied
QTc prevalence study in psychiatric patients (Reilly et al.)
How many people
596
Study design
Cross-sectional prevalence study with healthy reference group and logistic regression
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Abnormal QTc in 8 per cent (40 of 495); thioridazine odds ratio 5.4 (95% CI 2.0 to 13.7), droperidol 6.7 (1.8 to 24.8), tricyclics 4.4 (1.6 to 12.1), age over 65 3.0 (1.1 to 8.3), very high antipsychotic dose 8.2 (1.5 to 43.6)
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. QTc is a predictive marker rather than an outcome; no arrhythmic events are counted. Confidence intervals are wide, with the droperidol interval running from 1.8 to 24.8.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet or suspension
Interval reported. 95% CI 2
Written into the record, not signed off as a reviewed claim.
Drugs@FDA: MELLARIL (thioridazine hydrochloride), NDA 011808, Novartis — Discontinued (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overvi… · a recorded source, not a stored snapshot
Relationship of QTc interval to thioridazine dose, plasma concentration and CYP2D6 hydroxylation capacity
✓ The study showed what it set out to show
Who was studied
Thioridazine monotherapy QTc and CYP2D6 phenotype study
How many people
65
Study design
Prospective observational study with plasma concentration and enzyme phenotyping
Compared against
Not recorded for this study
Kind of result
What a body can do day to day
What was found
QTc over 420 ms in 35 of 65 (54 per cent); correlation with plasma concentration P < 0.05, daily dose P < 0.05, debrisoquine metabolic ratio P < 0.05, and thioridazine to mesoridazine ratio P < 0.05
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. A 420 ms threshold is substantially lower than the 456 ms used in the larger study, so the 54 per cent figure is not comparable to the 8 per cent prevalence there.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet or suspension
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Drugs@FDA: MELLARIL (thioridazine hydrochloride), NDA 011808, Novartis — Discontinued (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overvi… · a recorded source, not a stored snapshot
What we know
RNAWiki holds 2 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 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
Thioridazine
What a person takes: Oral tablet or suspension.
The measurement behind this step
Oral thioridazine hydrochloride, historically at daily doses extending into the hundreds of milligrams. Metabolised by CYP2D6 to the active metabolites mesoridazine and sulforidazine, with the parent inhibiting the same enzyme so that plasma concentration rises disproportionately with dose.
Getting in
Oral tablets or suspension, historically at high doses
Taken by mouth, often at high daily doses and for years at a time in chronic schizophrenia.
╌╌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
Oral thioridazine hydrochloride tablets or the Mellaril-S suspension. Dosing historically extended to several hundred milligrams daily, and the QTc effect is dose- and concentration-related across that range.
Metabolised by CYP2D6 into further active compounds
The liver converts it into two related compounds that are also active, using an enzyme the drug itself blocks.
╌╌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
CYP2D6-mediated oxidation to mesoridazine and sulforidazine, both pharmacologically active. Thioridazine inhibits CYP2D6, so its own clearance falls as concentration rises, and poor metabolisers reach higher exposures at the same dose.
Blocks dopamine D2 receptors — and the hERG potassium channel
It occupies dopamine receptors in the brain, which treats psychosis, and separately plugs a potassium channel in heart muscle.
╌╌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
Dopamine D2 antagonism in mesolimbic pathways gives the antipsychotic effect, with anticholinergic and alpha-adrenergic activity accounting for much of the side-effect profile. Independently, potent blockade of the hERG channel reduces the rapid delayed rectifier potassium current.
Ventricular repolarisation slows and the QT interval lengthens
Heart muscle cells take longer to reset after each beat, which shows on an electrocardiogram as a longer QT interval.
╌╌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
Reduced repolarising current prolongs the ventricular action potential and the QT interval, with increased transmural dispersion of repolarisation and a substrate for early afterdepolarisations and re-entry — the mechanism of torsades de pointes.
Psychosis controlled; QTc prolonged in a majority on monotherapy
It was an effective antipsychotic with less stiffness and tremor than the alternatives. More than half of patients on it alone had a prolonged QT interval.
──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
Measured: odds ratio 5.4 (95% CI 2.0 to 13.7) for QTc above 456 ms in 495 psychiatric patients. Measured: QTc above 420 ms in 54 per cent of 65 patients on monotherapy, correlated with dose, plasma concentration and CYP2D6 hydroxylation capacity.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 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 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.
Almost nobody. Drugs@FDA records Mellaril and most generic thioridazine products in Discontinued marketing status, and the surviving generic carries the restricted indication and boxed warning.
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 people who are pregnant, the label states: “Nonteratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.”
US prescribing information · 52fea941-0b47-41c1-b00d-f88150e8ab93 · read 2026-08-30
Where the result stopped carrying
Marketed from 1962 and restricted in July 2000 to patients who had failed adequate courses of other antipsychotics, with a boxed warning
The restriction rested on an electrocardiographic surrogate measured across a psychiatric population, not on counted arrhythmic deaths
Brand Mellaril and most generics are recorded in Drugs@FDA as Discontinued
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 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 change is too small to feel
A real change can still sit below what a person notices.
On this record: Droperidol, with a higher odds ratio in the same study, contested its warning successfully and returned; thioridazine did not
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)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
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.
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
Withdrawn
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet or suspension
✎ 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, S8.
No source is stored against this line.
What is in the pack
Oral thioridazine hydrochloride, historically at daily doses extending into the hundreds of milligrams. Metabolised by CYP2D6 to the active metabolites mesoridazine and sulforidazine, with the parent inhibiting the same enzyme so that plasma concentration rises disproportionately with dose.
✎ 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
Dose-related QTc prolongation is the reason for the restriction: odds ratio 5.4 (95% CI 2.0 to 13.7) for QTc above 456 ms in a psychiatric population, and QTc above 420 ms in 54 per cent of patients on monotherapy, correlated with dose, plasma concentration and CYP2D6 hydroxylation capacity. Torsades de pointes and sudden death are the feared consequences. Concurrent CYP2D6 inhibitors, genetic poor metaboliser status and electrolyte disturbance all raise exposure or susceptibility. Irreversible pigmentary retinopathy occurs at high cumulative doses and is a separate dose-limiting harm. Anticholinergic effects, orthostatic hypotension, sedation, sexual dysfunction and extrapyramidal symptoms apply as with other phenothiazines.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet or suspension
✎ 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
Metabolised by CYP2D6 to the active metabolites mesoridazine and sulforidazine, with the parent inhibiting the same enzyme so that plasma concentration rises disproportionately with dose.
✎ 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
22 products list this as an active ingredient in the United States drug directory. 22 of them contain it and nothing else.
FDA National Drug Code directory · 51079-580 · read 2026-08-29
They are sold as powder and tablet, film coated, taken oral.
FDA National Drug Code directory · 51079-580 · read 2026-08-29
The regulator's established pharmacologic class for it is phenothiazine [epc] and phenothiazines [cs].
FDA National Drug Code directory · 51079-580 · read 2026-08-29
5 published labels name it as an active ingredient. 5 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 52fea941-0b47-41c1-b00d-f88150e8ab93 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 52fea941-0b47-41c1-b00d-f88150e8ab93 · read 2026-08-29
Thioridazine Hydrochloride is oral at HOW SUPPLIED: Thioridazine Hydrochloride Tablets, USP are available containing 10 mg, 25 mg, 50 mg or 100 mg of thioridazine hydrochloride, USP., recorded as fda label in effect 2025-11-11 in the United States.
US prescribing information · 52fea941-0b47-41c1-b00d-f88150e8ab93 · read 2026-08-30
Recorded price in US: 0.38204–0.80237 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 14 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, withdrawn medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Thioridazine studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the proportion with prolonged QTc is the proportion at risk of fatal arrhythmia; the interval is a predictive marker, not the event
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 54 per cent and 8 per cent figures are comparable; they use thresholds of 420 ms and 456 ms respectively
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 thioridazine is formally withdrawn for safety — it is commercially discontinued and does not appear in 21 CFR 216.24
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 much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
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 Thioridazine 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.
Odds ratio 5.4 for abnormal QTc in 495 psychiatric patients
In plain words
Measuring electrocardiograms across 495 psychiatric patients and 101 healthy controls, thioridazine was one of the strongest predictors of a dangerously long QT interval.
What was measured
Odds ratio for QTc above 456 ms by psychotropic drug and by antipsychotic dose band
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Electrocardiograms from 101 healthy reference individuals and 495 psychiatric patients across inpatient and community settings were analysed with a validated digitiser technique, with logistic regression used to identify predictors. Abnormal QTc, defined from the healthy reference group as more than 456 ms, was present in 8 per cent of patients (40 of 495). Robust predictors were age over 65 (odds ratio 3.0, 95% CI 1.1 to 8.3), tricyclic antidepressants (4.4, 1.6 to 12.1), thioridazine (5.4, 2.0 to 13.7) and droperidol (6.7, 1.8 to 24.8), together with antipsychotic dose — high dose 5.3 (1.2 to 24.4) and very high dose 8.2 (1.5 to 43.6). Abnormal QT dispersion and T-wave abnormality were not associated with antipsychotic treatment but were associated with lithium. The authors conclude that antipsychotics prolong QTc in a dose-related manner with substantially higher risk for thioridazine and droperidol.
Written into the record, not signed off as a reviewed claim
QTc over 420 ms in 54 per cent on monotherapy, correlated with dose and level
In plain words
In 65 patients taking only thioridazine, more than half had a prolonged QT interval, and the length tracked both the dose and the blood concentration.
What was measured
Proportion with QTc over 420 ms, and its correlation with dose, plasma concentration and CYP2D6 metabolic ratio
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sixty-five Spanish psychiatric patients on thioridazine monotherapy were studied with plasma levels of thioridazine and its metabolites measured by high-performance liquid chromatography and CYP2D6 activity phenotyped with debrisoquine during treatment. Thirty-five patients (54 per cent) had a QTc interval over 420 ms. QTc lengthening correlated with plasma concentration (P < 0.05) and with daily dose (P < 0.05). It also correlated with CYP2D6 hydroxylation capacity as measured by the debrisoquine metabolic ratio (P < 0.05) and by the thioridazine to mesoridazine ratio (P < 0.05). The authors note that patients with impaired CYP2D6 activity, including impairment caused by thioridazine's own inhibition of the enzyme, may be at greater risk.
Written into the record, not signed off as a reviewed claim
The drug inhibits the enzyme that clears it, so risk compounds
In plain words
Thioridazine blocks the liver enzyme that breaks it down, so levels rise faster than the dose does — and higher levels mean a longer QT interval.
What was measured
Correlation of QTc with debrisoquine metabolic ratio and thioridazine to mesoridazine ratio
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Thioridazine is metabolised principally by CYP2D6 and is itself a potent inhibitor of that enzyme. The clinical study measured this directly, finding QTc correlated with the debrisoquine metabolic ratio and with the thioridazine to mesoridazine ratio, and its authors identify enzyme inhibition by thioridazine itself as a route to increased risk. The consequences are compounding: plasma concentration rises non-linearly with dose, poor metabolisers by genotype start at higher exposure, and any co-prescribed CYP2D6 inhibitor — including several antidepressants routinely given alongside antipsychotics — shifts the whole distribution. A dose that is safe in one patient is not necessarily safe in another taking the same amount.
Written into the record, not signed off as a reviewed claim
Sudden death in psychiatric patients was reclassified as a drug effect
In plain words
Unexplained sudden deaths among psychiatric inpatients had been attributed to the illness or the setting. Measuring the electrocardiogram made them a drug problem with a number attached.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Lancet study opens from the premise that sudden unexplained death in psychiatric patients may be due to drug-induced arrhythmia, with QTc lengthening as a predictive marker, and sets out to estimate its point prevalence. That framing is the shift. Before it, sudden death in this population was an epidemiological observation without an attributable mechanism, easily assigned to the illness, to physical restraint or to institutional care. Afterwards it was a measurable, dose-related, drug-specific effect on an interval that any electrocardiograph reports. Thioridazine's restriction in July 2000 to patients who had failed other antipsychotics, with a boxed warning for dose-related QTc prolongation, followed directly.
Written into the record, not signed off as a reviewed claim
QTc is a surrogate, and 8 per cent had an abnormal one without dying
In plain words
A long QT interval predicts a dangerous rhythm; it is not the rhythm itself. Most patients with a prolonged interval never have an arrhythmia.
What was measured
That the proportion of patients with prolonged QTc is the proportion at risk of fatal arrhythmia
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Lancet study measured QTc above 456 ms in 8 per cent of psychiatric patients and explicitly frames the interval as a predictive marker for drug-induced arrhythmia rather than as the outcome. The monotherapy study found QTc above 420 ms in 54 per cent of patients without reporting arrhythmic events. Torsades de pointes is rare even where QTc prolongation is common, and the relationship between the interval and the event is probabilistic and steeply non-linear. Restricting thioridazine on a surrogate is defensible: the surrogate is mechanistically direct, dose-related, and measurable, and there are alternatives. It remains a decision made on an interval rather than on counted deaths, and stating it as "thioridazine causes fatal arrhythmias in 8 per cent of patients" would misrepresent it entirely.
Written into the record, not signed off as a reviewed claim
The same study caught droperidol, with an even higher odds ratio
In plain words
Droperidol scored 6.7 in the same analysis that gave thioridazine 5.4. Both drugs were restricted within about eighteen months of it.
What was measured
Odds ratios for abnormal QTc: thioridazine 5.4, droperidol 6.7
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the same logistic regression, droperidol carried an odds ratio of 6.7 (95% CI 1.8 to 24.8) for abnormal QTc against thioridazine's 5.4 (2.0 to 13.7). Thioridazine was restricted with a boxed warning in July 2000 and droperidol received its own boxed warning in December 2001. The two drugs then diverged sharply in how the evidence was received: droperidol's warning was contested in the emergency medicine literature and the drug returned to wide use, while thioridazine's restriction was not seriously challenged and its market disappeared. The difference is not in the odds ratios, which overlap heavily. It is that droperidol had a distinctive clinical niche with no equivalent substitute, and thioridazine was one first-generation antipsychotic among several.
Written into the record, not signed off as a reviewed claim
The market disappeared, without a formal withdrawal-for-safety listing
In plain words
Mellaril and most generics are recorded as discontinued. Thioridazine does not appear on the federal list of drugs withdrawn for safety reasons.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Drugs@FDA records NDA 011808 (MELLARIL) and NDA 017923 (MELLARIL-S), Novartis, with products in Discontinued status, and most generic thioridazine applications are likewise discontinued, with at least one remaining in Prescription status. Thioridazine does not appear in 21 CFR 216.24, the codified list of drug products withdrawn or removed for reasons of safety or effectiveness, which carries rofecoxib, propoxyphene, rapacuronium, tegaserod and others. So the label restriction of July 2000 was followed by commercial abandonment rather than by regulatory removal. The distinction matters for the record: a drug can leave the market entirely on the strength of a warning that made it unsellable, without any document ever declaring it withdrawn.
Source
Drugs@FDA NDA 011808 and NDA 017923 (MELLARIL, MELLARIL-S, Novartis) — Discontinued; 21 CFR 216.24, which does not list thioridazine
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
Where else this substance is registered
FDA substance identifier (UNII)
N3D6TG58NI
CAS registry number
50-52-2
PubChem compound
5452
ChEMBL
CHEMBL479
ChEBI
48566
WHO international nonproprietary name list entry
818
RxNorm concept
10502
EMA substance identifier
100000082147
European Chemicals Agency number
200-044-2
DrugBank
DB00679
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Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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Suppression classes recorded: S6, S8.
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How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
Withdrawn in Worldwide, 2005, for "cardiotoxicity" (ChEMBL; Open Targets)
What the approval register records
81 approved applications cover products containing this substance. The earliest was NDA011808, approved 19620315 to NOVARTIS.
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What is not here
7 questions this page could not answer
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The older medicine-wide conclusion held in this record
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A first-generation antipsychotic restricted in 2000 and effectively withdrawn after electrocardiographic measurement in 495 psychiatric patients gave an odds ratio of 5.4 (95% CI 2.0 to 13.7) for abnormal QTc, with a separate study finding QTc over 420 ms in 54 per cent of patients on monotherapy and correlating the prolongation with dose, plasma concentration and CYP2D6 hydroxylation capacity.
Recorded evidence blocks (9)
Q2
On the Thioridazine label: indicated for what?
"Thioridazine hydrochloride tablets are indicated for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life threatening, proarrhythmic effects with thioridazine treatment, thioridazine hydrochloride tablets…": indications and usage on Thioridazine's label. DailyMed label · 1fd16a99-e856-4a37-9dae-c443714fac14 · 2026-03-02
Q3
6 registered trials of Thioridazine — at which phases?
"Primary objective not met after planned interim analysis"; 1 of 6 registered studies
Show the evidence
TrialNCT01765803
terminated; "Primary objective not met after planned interim analysis"
recorded 2026-09-01 · last checked 2026-09-04
Q6
Which 4 trials of Thioridazine posted no result?
Posted no result
4 of 4 completed trials
Registrations
NCT02582736, NCT02307396, NCT02096289 and NCT02600741
Completion dates
oldest 2012-12; newest 2018-07-05
Show the evidence
Trial
NCT02582736
2012-12
NCT02307396
2016-06-22
NCT02096289
2016-09
NCT02600741
2018-07-05
Q7
At the median, Thioridazine's trials enrolled 158.5 people — anything larger?
Median enrolment
158.5
Largest enrolment
725489
Registered trials counted
6
Q8
What do 69 spontaneous reports say about Thioridazine — 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.
Thioridazine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 69 reaction mentions were counted: drug hypersensitivity 16; suicide attempt 10; renal failure acute 7; thrombocytopenia 7. FAERS via Open Targets · CHEMBL1200916 · 2026-06-24
Show the evidence
drug hypersensitivity
16
suicide attempt
10
renal failure acute
7
thrombocytopenia
7
acute hepatic failure
6
neuroleptic malignant syndrome
6
4 more recorded rows
electrocardiogram qt prolonged
5
catatonia
4
delusion
4
parkinsonism
4
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Thioridazine's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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