Chlorpromazine (Thorazine): the first antipsychotic ever discovered

In 1952, a French navy surgeon named Henri Laborit was looking for a drug to calm patients before surgery. He noticed that one experimental compound — chlorpromazine — produced a strange "indifference" without sedation. He shared the observation with two psychiatric colleagues, Jean Delay and Pierre Deniker, who tried it on agitated psychotic patients at Sainte-Anne Hospital in Paris. Within weeks, they were watching patients with chronic, severe psychosis become calm enough to talk.

It was the first time in history that a medication had reliably reduced psychotic symptoms. Within a decade, chlorpromazine was prescribed to tens of millions of people worldwide, the asylum population in the US began to fall for the first time, and modern psychopharmacology was born.

How chlorpromazine works

Chlorpromazine is a phenothiazine and a low-potency typical antipsychotic. "Low-potency" doesn't mean weak — it means you need a higher milligram dose to achieve the same dopamine D2 blockade as a "high-potency" drug like haloperidol. Chlorpromazine is also a "dirty" drug pharmacologically: it blocks histamine H1, alpha-adrenergic, and muscarinic receptors strongly, in addition to dopamine. Those off-target effects explain its sedation, blood-pressure drops, dry mouth, and constipation.

What it treats

FDA-approved indications include:

• Schizophrenia and the manic phase of bipolar I disorder
• Severe behavioural disturbances in children
• Acute intermittent porphyria (an unusual indication)
• Tetanus (in combination with other treatments)
• Intractable hiccups
• Pre-operative apprehension
• Nausea and vomiting

In modern practice, the day-to-day use case for chlorpromazine in psychiatry is acute agitation in the inpatient setting, augmentation when sedation is needed alongside another antipsychotic, and chronic maintenance in patients who have done well on it for many years.

Forms and dosing

Chlorpromazine is available as oral tablets, oral concentrate, and an intramuscular injection. Daily doses for chronic psychosis are highly individual and span a wide range; specific dosing is between you and your prescriber.

The historical impact

Before 1952, treatment for schizophrenia consisted of insulin coma, electroconvulsive therapy, prolonged hydrotherapy, and lobotomy. Chlorpromazine changed everything in roughly five years. By 1955, the population of US state psychiatric hospitals had begun a long decline that continues to this day. Many historians credit chlorpromazine with making the modern outpatient model of psychiatric care possible. The story is told well in the chapter on chlorpromazine in the open-access NIH textbook on the history of psychiatric medications.

Side effects

Common

• Sedation — usually significant, especially in the first weeks
• Orthostatic hypotension — dizziness on standing, falls in older adults
• Anticholinergic effects — dry mouth, blurry vision, constipation, urinary hesitancy
• Photosensitivity — exaggerated sunburn risk; sunscreen and protective clothing matter
• Weight gain and metabolic changes — moderate, less than olanzapine but real
• Hyperprolactinaemia

Movement side effects

Chlorpromazine causes less acute EPS than high-potency typicals like haloperidol — but the long-term risk of tardive dyskinesia is similar. EPS still occurs, particularly with higher doses.

Less common but important

• Skin pigmentation — bluish-grey discolouration of sun-exposed skin with very long-term, high-dose use
• Pigmentary changes in the eye — corneal and lens deposits with long-term use
• Cholestatic jaundice — typically in the first weeks, requires evaluation
• QT prolongation on the ECG
• Neuroleptic malignant syndrome — rare, life-threatening (see warn-box below)

Where chlorpromazine still fits

• Acute agitation in inpatient psychiatry, particularly when sedation is desirable
• Patients who have been stable on it for years and tolerate it well
• Lower-resource settings where cost and availability matter
• Adjunctive use for severe nausea, hiccups, or palliative symptoms

Where it usually doesn't fit

• First-line outpatient maintenance in newly diagnosed patients (where atypicals are usually preferred)
• Older adults at risk of falls
• People with significant cardiac conduction problems
• People with dementia (FDA boxed warning across the antipsychotic class)

Practical points

• Wear sunscreen and a hat outdoors — sunburns can be severe
• Stand up slowly to limit dizziness
• Have liver function and ECG checked at baseline
• Talk to your prescriber before stopping — abrupt withdrawal can cause cholinergic rebound

A historical drug, still on the menu

Chlorpromazine is a 70-year-old molecule. Newer drugs are usually preferred for new starts. But the medication that began modern psychiatry remains, in 2026, on the WHO Essential Medicines List — and for the right patient, it can quietly do its job for decades.

This article is for educational purposes only and is not medical advice. Information is summarised from publicly available FDA labelling and peer-reviewed literature. Always consult your prescribing clinician before starting, stopping, or changing any medication. If you or someone you know is in crisis, call or text 988 in the US, or your local emergency number.