Chlorpromazine is the molecule that defined an era. When it was introduced into clinical use in 1952 by the French psychiatrists Jean Delay and Pierre Deniker, it was the first medication that could reliably reduce hallucinations, delusions, and agitation in people with schizophrenia. Within a decade it had transformed the inpatient population of Western psychiatric hospitals, and within two decades the entire field of antipsychotic pharmacology had grown out of attempts to copy or improve on it. Seven decades later it is still on the market — sold in the US under the brand Thorazine, in much of the world as Largactil, and in many countries as a generic.
Chlorpromazine is a low-potency phenothiazine antipsychotic that pioneered the field and is still used selectively for schizophrenia, severe agitation, intractable hiccups, and a few other indications, with a sedating, anticholinergic profile that limits day-to-day use.
Where it came from
Chlorpromazine was synthesised at Rhône-Poulenc in 1950 as part of work on antihistamines that could be used as surgical premedications. The French surgeon Henri Laborit noticed that it produced an unusual calm — a "euphoric quietude" — in patients before anaesthesia. He suggested colleagues try it in psychiatric patients. By 1952 Delay and Deniker had reported its use in agitated psychotic patients at Sainte-Anne hospital in Paris. By 1954 it was approved in the US as Thorazine. The story is detailed in many histories of psychopharmacology, including the resources at the American College of Neuropsychopharmacology.
How it works
Chlorpromazine binds to many receptors. The most clinically relevant include dopamine D2 (the basis of antipsychotic effect), histamine H1 (sedation, weight gain), muscarinic acetylcholine (dry mouth, constipation, blurred vision), and alpha-1 adrenergic (orthostatic hypotension). Compared with later "high-potency" first-generation drugs such as haloperidol, chlorpromazine has weaker D2 binding per milligram — which is why doses are higher (hundreds of milligrams) and why anticholinergic and antihistamine effects dominate the side effect picture.
FDA-approved indications
According to the DailyMed chlorpromazine label, US-approved uses include:
- Schizophrenia (manifestations of psychotic disorders)
- Manic-type bipolar disorder, short-term treatment
- Severe behavioural problems in children with combativeness or hyperexcitability
- Nausea and vomiting
- Relief of restlessness and apprehension before surgery
- Acute intermittent porphyria
- Tetanus (as adjunct)
- Intractable hiccups
The non-psychiatric indications are reminders that chlorpromazine was developed in part as a general "broad-spectrum" sedative — its uses spread well beyond schizophrenia in the 1950s and 1960s.
Typical dosing
Per the FDA label, oral schizophrenia doses range from roughly 200 to 800 mg per day in divided doses, occasionally higher in inpatient settings. Intramuscular doses for acute agitation typically start at 25 mg. Doses for hiccups or nausea are much lower (often 10–25 mg). Older adults are started at the lowest possible dose because of orthostatic hypotension and fall risk.
Side effects
Sedation and anticholinergic burden
Most patients are noticeably sedated, especially in the first weeks. Dry mouth, constipation, urinary retention, and blurred vision are common. See our overviews of dry mouth and antipsychotic constipation.
Orthostatic hypotension
Strong alpha-1 blockade can cause dizziness on standing, particularly in older adults. Slow position changes and adequate hydration help.
Movement disorders
Acute dystonia, parkinsonism, akathisia, and — over years — tardive dyskinesia can occur. Rates of acute EPS are lower than with high-potency typicals like haloperidol but not zero.
Photosensitivity and pigmentation
Chlorpromazine is famous for two skin-related effects: pronounced sun sensitivity (sunburn after brief exposure) and, with long-term high-dose use, slate-grey skin pigmentation in sun-exposed areas. Sunscreen and protective clothing are essential. See our photosensitivity guide.
Cardiovascular
QT prolongation can occur. ECG monitoring is reasonable in patients with risk factors. See QT prolongation overview.
Hepatic and haematologic
Cholestatic jaundice and rare blood dyscrasias have been reported with chlorpromazine since the 1950s. Liver function and CBC monitoring are reasonable in long-term use.
You develop severe muscle stiffness with high fever and confusion (possible neuroleptic malignant syndrome), severe sudden involuntary movements, or signs of a serious allergic reaction.
Boxed warning
Like other antipsychotics, chlorpromazine carries the FDA boxed warning about increased mortality in elderly patients with dementia-related psychosis. It should not be used to treat behavioural symptoms of dementia.
Drug interactions
Chlorpromazine adds to the effects of other CNS depressants (alcohol, benzodiazepines, opioids), can lower the seizure threshold (relevant when combined with bupropion or tramadol), and interacts with several QT-prolonging drugs. Always tell prescribers about all medications and supplements.
Where chlorpromazine still fits in 2026
Modern guidelines from NICE and the American Psychiatric Association generally recommend second-generation antipsychotics first for schizophrenia, but chlorpromazine retains a place when:
- Other agents have failed and clozapine is not appropriate or available
- Severe agitation requires a sedating antipsychotic
- Cost is a major issue and generics are needed
- Specific non-psychiatric indications apply (intractable hiccups, terminal nausea)
- In low- and middle-income settings where generic availability is the most reliable factor
Practical questions to ask your prescriber
- Why this drug rather than a newer agent?
- What baseline ECG, liver tests, and CBC do I need?
- How will we manage sedation and orthostatic dizziness?
- What sun protection plan is needed?
The big picture
Chlorpromazine is no longer a first-line drug in most settings, but its place in psychiatric history is secure and its clinical utility has not vanished. For some patients — particularly those who have done poorly on newer agents, who need the sedating profile, or who live in healthcare systems where generic chlorpromazine is the most accessible option — it remains a workable choice when used carefully. The conversation about whether it fits is best had with a prescriber who knows your full medication and side-effect history.
This article is for educational purposes only and is not medical advice. Information is summarised from publicly available FDA labelling, regulatory sources, and peer-reviewed literature. Always consult your prescribing clinician before starting, stopping, or changing any medication.