This page shows what was measured, who it was measured in, and what that does not settle.
What Paliperidone does in the body
Schizophrenia, and schizoaffective disorder
When someone swallows risperidone, the liver converts most of it into a second molecule that does the same job. Paliperidone is that second molecule, purified and sold on its own. It blocks the dopamine receptor that dampens hallucinations and delusions, and blocks a serotonin receptor at the same time. Because it skips the conversion step, it is less affected by the liver enzymes that vary between people, and it is chemically better suited to being made into an injection that lasts one, three or six months.
What happened in people
A standardised mean difference of 0.50 against placebo for overall symptom change, fifth of fifteen ranked antipsychotics
✎ 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.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
The limit that matters most
The only drug in the United States with a specific indication for schizoaffective disorder
Where it acts
Mesolimbic and mesocortical dopamine synapses, and the tuberoinfundibular pathway, where D2 blockade removes the brake on prolactin release from the pituitary
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
The substance registry classes this as chemical.
FDA substance registry · 838F01T721 · read 2026-08-29
Its recorded molecular formula is C23H27FN4O3, weighing 426.49.
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 110 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
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.
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.
Change in PANSS total score, flexible-dose paliperidone palmitate against flexible-dose long-acting intramuscular risperidone in schizophrenia
PANSS change -18.6 on paliperidone palmitate against -17.9 on long-acting risperidone; mean difference 0.4 (95% CI -1.62 to 2.38) against a five-point non-inferiority margin
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The trial establishes equivalence, not advantage. It was run by the company that owns both products, which makes the null result harder to attribute to a comparator being handicapped.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablet taken once daily, and paliperidone palmitate intramuscular injections given monthly, three-monthly or six-monthly
Interval reported. 95% CI -1
Written into the record, not signed off as a reviewed claim.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
United States prescribing information for paliperidone extended-release tablets, sections 2.1, 2.3, 5.7, 5.8, 12.1, 12.2 and 14.1, via the openFDA drug label… · a recorded source, not a stored snapshot
Percentage of participants without relapse at week 48, three-month against one-month paliperidone palmitate formulation
91.5% relapse-free on the three-month formulation against 90.0% on the one-month formulation at week 48
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The comparator is the sponsor's own earlier formulation of the same molecule. No arm tested a different drug, and no arm tested generic risperidone.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablet taken once daily, and paliperidone palmitate intramuscular injections given monthly, three-monthly or six-monthly
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
United States prescribing information for paliperidone extended-release tablets, sections 2.1, 2.3, 5.7, 5.8, 12.1, 12.2 and 14.1, via the openFDA drug label… · a recorded source, not a stored snapshot
Change from baseline in PANSS total score at week 6, with the Personal and Social Performance scale as a co-measure, at 3, 6, 9, 12 and 15 mg daily
Three randomised placebo-controlled and olanzapine-controlled 6-week fixed-dose trials
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Superior to placebo on the PANSS at all doses; the label records that mean effects at all doses were fairly similar and higher doses only numerically superior
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. A five-fold dose range produced an essentially flat response, which the label states plainly and which argues against the intuition that a higher amount does more.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablet taken once daily, and paliperidone palmitate intramuscular injections given monthly, three-monthly or six-monthly
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
United States prescribing information for paliperidone extended-release tablets, sections 2.1, 2.3, 5.7, 5.8, 12.1, 12.2 and 14.1, via the openFDA drug label… · a recorded source, not a stored snapshot
Mean overall change in symptoms against placebo in acute schizophrenia, with all-cause discontinuation, weight gain, extrapyramidal effects, prolactin, QTc and sedation as secondary outcomes
✓ The study showed what it set out to show
Who was studied
Leucht 15-drug multiple-treatments meta-analysis
How many people
43049
Study design
Bayesian network meta-analysis of 212 blinded randomised trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Paliperidone standardised mean difference 0.50 (95% CrI 0.39 to 0.60), fifth of fifteen; prolactin effect -1.30, the least favourable of the fifteen
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. Paliperidone and risperidone, the metabolite and its parent, sit adjacent in the ranking at 0.50 and 0.56, which is what a shared active molecule predicts.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral extended-release tablet taken once daily, and paliperidone palmitate intramuscular injections given monthly, three-monthly or six-monthly
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
United States prescribing information for paliperidone extended-release tablets, sections 2.1, 2.3, 5.7, 5.8, 12.1, 12.2 and 14.1, via the openFDA drug label… · a recorded source, not a stored snapshot
What we know
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 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
Paliperidone
What a person takes: Oral extended-release tablet taken once daily, and paliperidone palmitate intramuscular injections given monthly, three-monthly or six-monthly.
The measurement behind this step
The oral tablet is a non-deformable extended-release unit that must be swallowed whole and not chewed, divided or crushed, and the label carries a separate gastrointestinal narrowing warning for patients with gastrointestinal disease. The injectables are nanocrystal suspensions of the palmitate ester, which dissolves slowly from muscle and is hydrolysed back to paliperidone; release rate is set by particle size. The 9-position hydroxyl that distinguishes paliperidone from risperidone is what makes that ester possible, and it is the clearest technical justification for the product existing separately.
Getting in
A rigid daily tablet, or an injection lasting one, three or six months
The oral form is a once-daily tablet that must be swallowed whole. The injectable forms are given once a month, once every three months, or twice a year.
╌╌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 oral product is an extended-release tablet delivering drug at a controlled rate through a non-deformable shell, which is why it must not be chewed, divided or crushed and why the label carries a gastrointestinal narrowing warning. The injectables are aqueous nanocrystal suspensions of paliperidone palmitate; release rate is governed by particle dissolution from the muscle rather than by a polymer.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
Reaching the cell
It skips the liver conversion step that risperidone depends on
Risperidone has to be converted by the liver into this molecule before much of its work is done. Paliperidone arrives already converted, so how fast a person's liver works matters much less.
╌╌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
Risperidone is hydroxylated to 9-hydroxyrisperidone by CYP2D6, an enzyme with well-characterised poor, intermediate, extensive and ultra-rapid metaboliser phenotypes. Paliperidone is that hydroxylated product, and it is not extensively metabolised: about 59% of a dose is excreted unchanged in urine, and no single hepatic pathway dominates its clearance. The palmitate ester of the injectable is hydrolysed back to paliperidone after dissolution from the muscle.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
What it acts on
It blocks dopamine D2 and serotonin 5-HT2A
It switches off the dopamine receptor that dampens hallucinations and delusions, and switches off a serotonin receptor alongside it. That combination is what the whole second-generation class is built on.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Antagonism at D2 with Ki 1.6 to 2.8 nM and at 5-HT2A with Ki 0.8 to 1.2 nM, plus antagonism at alpha-1 and alpha-2 adrenergic and H1 histaminergic receptors. No affinity for muscarinic or beta-adrenergic receptors, which is why anticholinergic effects are largely absent. The label states the pharmacological activity of the two enantiomers is qualitatively and quantitatively similar in vitro.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
The change it makes
The same blockade reaches the pituitary and prolactin rises
Dopamine is the brake that keeps the pituitary gland from releasing prolactin. Blocking dopamine releases the brake, and prolactin goes up and stays up for as long as the drug is taken.
╌╌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
D2 blockade in the tuberoinfundibular pathway removes tonic dopaminergic inhibition of lactotroph prolactin secretion. In the fifteen-drug network meta-analysis paliperidone had the least favourable prolactin effect of all fifteen at a standardised mean difference of -1.30. Section 5.7 of the label states the elevation occurs and persists during chronic administration, and the clinical consequences are amenorrhoea, galactorrhoea, gynaecomastia and sexual dysfunction.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
What that does for a person
Symptoms fall, relapse is delayed, hormones move
The effect on symptoms is toward the better end of what antipsychotics achieve. The long-acting injections genuinely delay relapse. The price is the largest hormonal disturbance in the class.
╌╌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
Standardised mean difference against placebo of 0.50 (95% CrI 0.39 to 0.60) for overall symptom change, fifth of fifteen. Against long-acting risperidone the difference was 0.4 PANSS points (95% CI -1.62 to 2.38). In the three-month versus one-month injectable comparison, 91.5% against 90.0% remained relapse-free at 48 weeks. Prolactin effect last of fifteen at -1.30.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · 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 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.
Adults and adolescents from age 12 with schizophrenia, and adults with schizoaffective disorder, which is the only drug-specific indication for that diagnosis in the United States. The injectable forms are used most where taking a daily tablet is the step that fails.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness of paliperidone extended-release tablets in the treatment of schizophrenia were evaluated in 150 adolescent subjects 12 to 17 years of age with schizophrenia who received paliperidone extended-release tablets in the dose range of 1.5 mg to 12 mg/day in a 6-week, double-blind, placebo-controlled trial.”
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-30
On older people, the label states: “The safety, tolerability, and efficacy of paliperidone extended-release tablets were evaluated in a 6-week placebo-controlled study of 114 elderly subjects with schizophrenia (65 years of age and older, of whom 21 were 75 years of age and older).”
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-30
On people who are pregnant, the label states: “Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including paliperidone extended-release tablets, during pregnancy.”
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Limited data from published literature report the presence of paliperidone in human breast milk.”
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-30
On people with reduced liver function, the label states: “No dosage adjustment is required in patients with mild to moderate hepatic impairment.”
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-30
On people with reduced kidney function, the label states: “Dosing must be individualized according to the patient’s renal function status [see Dosage and Administration (2.5)] .”
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-30
Where the result stopped carrying
The head-to-head trial against long-acting risperidone found a difference of 0.4 PANSS points, which is the sponsor's own measurement of what the newer molecule adds pharmacologically
Paliperidone finished last of fifteen on prolactin in the same analysis that placed it fifth on efficacy
The oral extended-release tablet carries its own gastrointestinal narrowing warning, a formulation problem rather than a pharmacological one
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 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 (11)
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.
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
Given by a clinician
❝ 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 extended-release tablet taken once daily, and paliperidone palmitate intramuscular injections given monthly, three-monthly or six-monthly
✎ 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, S9.
No source is stored against this line.
What is in the pack
The oral tablet is a non-deformable extended-release unit that must be swallowed whole and not chewed, divided or crushed, and the label carries a separate gastrointestinal narrowing warning for patients with gastrointestinal disease.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: The injectables are nanocrystal suspensions of the palmitate ester, which dissolves slowly from muscle and is hydrolysed back to paliperidone; release rate is set by particle size. The 9-position hydroxyl that distinguishes paliperidone from risperidone is what makes that ester possible, and it is the clearest technical justification for the product existing separately.
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
The United States label carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis. Section 5.7 states that prolactin elevations occur and persist during chronic administration, and paliperidone had the largest prolactin effect of the fifteen antipsychotics ranked head to head. Section 5.8 warns of gastrointestinal narrowing with the oral extended-release tablet. Neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes including hyperglycaemia and dyslipidaemia, orthostatic hypotension and syncope, leukopenia, neutropenia and agranulocytosis, seizures and cognitive and motor impairment are all in the label. There is no anticholinergic burden, because the drug has no muscarinic affinity.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
NCT00589914 — randomised double-blind comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results (NCT00589914) · a recorded source, not a stored snapshot
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results (NCT01515423) · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral extended-release tablet taken once daily, and paliperidone palmitate intramuscular injections given monthly, three-monthly or six-monthly
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
The injectables are nanocrystal suspensions of the palmitate ester, which dissolves slowly from muscle and is hydrolysed back to paliperidone; release rate is set by particle size. The 9-position hydroxyl that distinguishes paliperidone from risperidone is what makes that ester possible, and it is the clearest technical justification for the product existing separately.
✎ 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
83 products list this as an active ingredient in the United States drug directory. 83 of them contain it and nothing else.
FDA National Drug Code directory · 72162-2651 · read 2026-08-29
They are sold as powder, tablet, extended release and tablet, film coated, extended release, taken oral.
FDA National Drug Code directory · 72162-2651 · read 2026-08-29
The regulator's established pharmacologic class for it is atypical antipsychotic [epc].
FDA National Drug Code directory · 72162-2651 · read 2026-08-29
25 published labels name it as an active ingredient. 25 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-29
paliperidone is oral at 3 DOSAGE FORMS AND STRENGTHS Paliperidone extended-release tablets are available in the following strengths and colors: 1.5 mg (orange-brown), 3 mg (white), 6 mg (beige), and 9 mg (pink)., recorded as fda label in effect 2024-09-30 in the United States.
US prescribing information · be30f3cc-55fb-4a74-9778-60573a7f18c6 · read 2026-08-30
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 Paliperidone 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 paliperidone is a distinct therapeutic advance over risperidone — its own label identifies it as risperidone's major active metabolite
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 three-month and six-month injections improve outcomes over the one-month — every trial in that chain was designed to show non-inferiority to its predecessor
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 higher amount produces a proportionally larger effect — the registration data across a five-fold range are flat
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 size of the relapse-prevention benefit is established — the maintenance trial was stopped early and the label reports no effect estimate
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 Paliperidone are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
A new drug that the body was already making from an old one
In plain words
Paliperidone is the molecule your liver turns risperidone into. It was approved as a separate medicine in 2006. Risperidone's first generic versions were approved in October 2008.
What was measured
That paliperidone represents a new therapeutic mechanism — its own label identifies it as the major active metabolite of a drug approved in 1993
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 12.1 of the United States prescribing information states directly: "Paliperidone is the major active metabolite of risperidone." Paliperidone extended-release tablets were approved under NDA 021999 in 2006. The earliest abbreviated new drug applications for risperidone were approved from 16 October 2008 onward, according to the Drugs@FDA application records. The sequence is a fact about dates rather than an accusation about intent, and it is the single most useful thing to know when reading a comparison between the two. Note also what the metabolite genuinely bought: paliperidone carries a 9-position hydroxyl that risperidone does not, and that hydroxyl is what allows a palmitate ester and therefore an injection lasting one, three or six months. The delivery advance is real. The efficacy question was largely answered before the first paliperidone trial began.
Source
United States prescribing information for paliperidone, section 12.1, via the openFDA drug label endpoint; Drugs@FDA records for NDA 021999 and for risperidone ANDA approvals from October 2008
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
Head to head against long-acting risperidone, the difference was 0.4 PANSS points
In plain words
Janssen ran its own monthly injection against the older risperidone injection in 1,221 patients. The two were separated by less than half a point on a scale that runs from 30 to 210.
What was measured
Mean difference in PANSS total score change: 0.4 (95% CI -1.62 to 2.38) against a five-point non-inferiority margin
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
NCT00589914, a randomised double-blind parallel-group comparison of flexible doses of paliperidone palmitate against flexible doses of long-acting intramuscular risperidone, enrolled 1,221 patients with schizophrenia. Mean change in PANSS total score was -18.6 for paliperidone palmitate against -17.9 for Risperdal Consta, a difference of 0.4 with a 95% confidence interval from -1.62 to 2.38 against a pre-specified non-inferiority margin of five points. This is the cleanest available measurement of what the newer product adds pharmacologically, it was generated by the company that owns both, and the answer it gives is nothing detectable. The advantage of paliperidone palmitate is a dosing interval, not a stronger effect.
Source
NCT00589914 — randomised comparison of paliperidone palmitate and long-acting intramuscular risperidone, posted results, Johnson & Johnson Pharmaceutical Research & Development
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 largest prolactin elevation of the fifteen antipsychotics ranked
In plain words
Across 212 trials and 43,049 patients, paliperidone raised prolactin more than any other antipsychotic in the comparison. The label states the elevation persists for as long as the drug is taken.
What was measured
Standardised mean difference against placebo for prolactin increase: -1.30, the least favourable of fifteen drugs
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the Leucht multiple-treatments meta-analysis, standardised mean differences against placebo for prolactin increase ran from 0.22 for aripiprazole at the favourable end to -1.30 for paliperidone at the unfavourable end. Paliperidone therefore holds both ends of a genuine trade in this dataset: fifth of fifteen on symptom reduction with a standardised mean difference of 0.50 (95% CrI 0.39 to 0.60), and last of fifteen on prolactin. Section 5.7 of the United States label states that prolactin elevations occur and persist during chronic administration. Sustained hyperprolactinaemia produces amenorrhoea, galactorrhoea, gynaecomastia and sexual dysfunction, and is measurable with a single blood test that is not routinely ordered.
Written into the record, not signed off as a reviewed claim
The three-month and six-month injections were tested against the one-month, not against anything better
In plain words
The longer-acting versions of this drug were approved by showing they were no worse than the shorter-acting version of the same drug. No trial asked whether they beat an alternative.
What was measured
That a three-month or six-month injection produces better outcomes than a one-month injection — the trials were designed to show non-inferiority to the predecessor product, not superiority over anything
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
NCT01515423 was a randomised double-blind non-inferiority study of the three-month against the one-month paliperidone palmitate formulation in 1,429 patients. The percentage without relapse at week 48 was 91.5% on the three-month formulation and 90.0% on the one-month formulation. The three-month product was approved under NDA 207946 with an original approval date of 18 May 2015, and the six-month product was added to the same application later. Each formulation in the chain is established against its own predecessor. That design answers the question of whether a longer interval is safe to substitute, and it is the right design for that question. It does not measure whether a longer interval improves any outcome, and it never compares the franchise against a different drug or against generic risperidone.
Source
NCT01515423 — non-inferiority study of paliperidone palmitate three-month and one-month formulations, posted results; Drugs@FDA NDA 207946, original approval 18 May 2015
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
A five-fold dose range with, in the label's own words, fairly similar effects
In plain words
The three registration trials tested amounts from 3 mg to 15 mg a day. The label reports that the effects at all of those amounts were fairly similar, with the higher ones only numerically better.
What was measured
That a higher amount of paliperidone produces a proportionally larger effect — the registration data across a five-fold range are described in the label itself as fairly similar
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 14.1 of the United States prescribing information describes three placebo-controlled and olanzapine-controlled six-week fixed-dose trials in 1,665 adults, at 3, 6, 9, 12 and 15 mg daily. It states that paliperidone was superior to placebo on the PANSS at all doses, that mean effects at all doses were fairly similar, and that the higher doses were only numerically superior. A five-fold range producing an essentially flat response is what would be expected if D2 occupancy is already near its ceiling at the lowest amount tested, which means the dose-finding data do not support the intuition that more drug does more work. The label reflects this: the recommended adult amount is 6 mg with no initial titration required.
Source
United States prescribing information for paliperidone, sections 2.1 and 14.1, via the openFDA drug label endpoint
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
The maintenance trial was stopped early at an interim analysis
In plain words
The trial that established paliperidone keeps schizophrenia from coming back was halted before it finished, because an interim look showed the drug was working. Trials stopped this way tend to report larger effects than trials that run to completion.
What was measured
That the size of the relapse-prevention effect is established — the trial was terminated at an interim analysis and the label reports no effect estimate for it
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 14.1 of the label describes a randomised withdrawal design: an eight-week run-in, a six-week open-label stabilisation phase, then randomisation to continue paliperidone or switch to placebo until relapse. It records that an interim analysis showed a significantly longer time to relapse on paliperidone and that the trial was stopped early because maintenance of efficacy was demonstrated. Stopping early for benefit is standard and ethically defensible practice. It is also a well-documented source of effect-size inflation, because a trial is most likely to cross a stopping boundary at a moment when random variation is running in the drug's favour. The direction of the finding is not in doubt here. Its magnitude is less certain than a completed trial's would have been, and the label does not report a hazard ratio or a p-value for it.
Source
United States prescribing information for paliperidone, section 14.1, via the openFDA drug label endpoint
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
A rigid tablet with its own gastrointestinal warning
In plain words
The oral tablet releases its contents through a rigid shell over the course of the day. It must be swallowed whole, and the label warns that in people with gastrointestinal disease it can cause obstruction symptoms.
What was measured
The text of the approved United States label, sections 2.3 and 5.8
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 2.3 of the United States label states that the tablet should be swallowed whole and should not be chewed, divided or crushed. Section 5.8 carries a distinct warning headed Gastrointestinal Narrowing, stating that obstructive symptoms may result in patients with gastrointestinal disease. This is a consequence of the delivery system rather than of the molecule: the extended-release tablet is a non-deformable unit that passes through the gut largely intact. It is the reason a person with strictures, a history of bowel surgery or severe dysphagia is a poor candidate for this specific formulation while being a perfectly reasonable candidate for the same drug given by injection.
Source
United States prescribing information for paliperidone, sections 2.3 and 5.8, via the openFDA drug label endpoint
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
How many documents were read
25 documents were read for this substance.
RNAWiki source record
25 of them state the same halfLife, and they agree.
RNAWiki source record
9 of them state the same bioavailability, and they agree.
RNAWiki source record
25 of them state the same tMax, and they agree.
RNAWiki source record
25 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
838F01T721
RxNorm concept
672567
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✓ Passed
Safety mode resolved
Suppression classes recorded: S6, S9.
✓ Passed
Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
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.
What the approval register records
17 approved applications cover products containing this substance. The earliest was NDA021999, approved 20061219 to JANSSEN PHARMS.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 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 was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
Risperidone's major active metabolite sold as a separate medicine, ranked fifth of fifteen antipsychotics on symptom reduction, carries the largest prolactin elevation of all fifteen, performed indistinguishably from long-acting risperidone when the two were put head to head in 1,221 patients, and costs about fifteen times as much per tablet as the drug it is derived from.
Recorded evidence blocks (10)
Q2
On the Paliperidone label: indicated for what?
"1. INDICATIONS AND USAGE Paliperidone is an atypical antipsychotic agent indicated for Treatment of schizophrenia ( 1.1 ) Adults: Efficacy was established in three 6-week trials and one maintenance trial.": indications and usage on Paliperidone's label. DailyMed label · bbbaa057-f587-4eb9-a0d2-463dbcd57661 · 2026-07-28
Q3
96 registered trials of Paliperidone — at which phases?
23 hours; The terminal elimination half-life of paliperidone is approximately 23 hours.
tmaxpharmacokinetics
24 hours; Following a single dose, the plasma concentrations of paliperidone gradually rise to reach peak plasma concentration (C max ) approximately 24 hours after dosing.
bioavailabilitypharmacokinetics
28 %; Absorption and Distribution The absolute oral bioavailability of paliperidone following paliperidone extended-release tablet administration is 28%.
metabolismpharmacokinetics
Metabolism and Elimination Although in vitro studies suggested a role for CYP2D6 and CYP3A4 in the metabolism of paliperidone, in vivo results indicate that these isozymes play a limited role in the overall elimination of paliperidone [see Drug Interactions (7) ].
recorded 2026-07-28 · last checked 2026-09-04
Q7
Which 42 trials of Paliperidone posted no result?
Posted no result
42 of 42 completed trials
Registrations
NCT00073320, NCT00257023, NCT00101634, NCT01110317, NCT00210548 and NCT00668837, and 36 more
Completion dates
oldest 2004-05; newest 2022-10-23
Show the evidence
Trial
NCT00073320
2004-05
NCT00257023
2005-09
NCT00101634
2006-03
NCT01110317
2006-03
NCT00210548
2006-06
NCT00668837
2006-06
14 further recorded trials
NCT00119756
2006-11
NCT00210717
2007-04
NCT00299715
2007-06
NCT00111189
2008-02
NCT03730857
2008-12
NCT01942382
2010-03
NCT00827840
2011-02
NCT00915512
2011-10
NCT01607762
2012-10
NCT01258920
2012-11
NCT02582736
2012-12
NCT01362426
2013-05
NCT01051531
2013-05-17
NCT01682161
2013-09
Q8
At the median, Paliperidone's trials enrolled 177.5 people — anything larger?
Median enrolment
177.5
Largest enrolment
1037352
Registered trials counted
96
Q9
What do 2426 spontaneous reports say about Paliperidone — 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.
Paliperidone appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2426 reaction mentions were counted: dystonia 324; suicide attempt 288; weight increased 262; sedation 244. FAERS via Open Targets · CHEMBL1621 · 2026-06-24
Show the evidence
dystonia
324
suicide attempt
288
weight increased
262
sedation
244
dyskinesia
230
schizophrenia
228
4 more recorded rows
galactorrhoea
223
hospitalisation
214
blood prolactin increased
211
extrapyramidal disorder
202
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Paliperidone's label not list?
( 7.1 ) Strong CYP3A4/P-glycoprotein (P-gp) inducers: It may be necessary to increase the dose of paliperidone when a strong inducer of both CYP3A4 and P-gp (e.g., carbamazepine) is co-administered.
drug_interactions
Paliperidone is not expected to cause clinically important pharmacokinetic interactions with drugs that are metabolized by cytochrome P450 isozymes.
drug_interactions
In vitro studies in human liver microsomes showed that paliperidone does not substantially inhibit the metabolism of drugs metabolized by cytochrome P450 isozymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5.
drug_interactions
Paliperidone is a weak inhibitor of P-glycoprotein (P-gp) at high concentrations.
drug_interactions
7.2 Potential for Other Drugs to Affect Paliperidone Paliperidone is not a substrate of CYP1A2, CYP2A6, CYP2C9, and CYP2C19, so that an interaction with inhibitors or inducers of these isozymes is unlikely.
drug_interactions
While in vitro studies indicate that CYP2D6 and CYP3A4 may be minimally involved in paliperidone metabolism, in vivo studies do not show decreased elimination by these isozymes and they contribute to only a small fraction of total body clearance.
2 more recorded rows
Interaction statementdrug_interactions
In vitro studies have shown that paliperidone is a P-gp substrate.
Interaction statementdrug_interactions
Co-administration of paliperidone 6 mg once daily with carbamazepine, a strong inducer of both CYP3A4 and P-glycoprotein (P-gp), at 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state C max and AUC of paliperidone.
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · 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
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.