Psychology › Therapy & treatment › Psychiatric medicine: drugs and brain treatments
Antipsychotic medications
1952 (chlorpromazine); Cobenfy 2024· Therapy or method
Well replicatedStrong, repeated evidence.
Drugs that reduce hallucinations, delusions and disordered thinking in psychosis, most of them by blocking dopamine signals.
See it on the Psychology map →What it says
In 1952 Paris psychiatrists Jean Delay and Pierre Deniker found that chlorpromazine, which surgeon Henri Laborit had tried as a pre-surgery calming drug, eased psychosis. Haloperidol followed in 1958. These first-generation drugs often caused stiffness and tremor and, with long use, tardive dyskinesia, an involuntary movement disorder. Second-generation drugs from the 1990s, such as risperidone and olanzapine, cause fewer movement problems but more weight gain. Clozapine helps when others fail. Cobenfy (2024) is the first schizophrenia drug that does not directly block dopamine.
Why it matters
They let many people with schizophrenia live outside long-term hospitals and remain the backbone of treatment for psychosis and for bipolar mania.
The evidence
Status: well replicated. Placebo-controlled trials since the 1950s and large meta-analyses, notably Stefan Leucht's group in Munich, show clear benefit for acute psychosis and for preventing relapse.
Open questions
Many patients get only partial relief, and why clozapine works when others fail is unknown. How long to continue medication after recovery is debated.
Connections (4)
▸Antipsychotic medications mostly block receptors for Dopamine, reward and prediction errorWell replicated
The connection
Most antipsychotics block dopamine D2 receptors, damping signals in brain pathways thought to be overactive in psychosis. The doses that work track how tightly each drug binds D2. Blocking dopamine in movement circuits also explains their Parkinson-like side effects. This evidence produced the 'dopamine hypothesis' of schizophrenia.
Who showed it and when
Arvid Carlsson linked antipsychotics to dopamine in 1963; in 1975–76 Philip Seeman in Toronto and Solomon Snyder at Johns Hopkins showed clinical doses match D2 binding strength.
The evidence
PET brain scans show the drugs work best when they occupy roughly 65 to 80 percent of D2 receptors; amphetamine, which releases dopamine, can trigger psychosis.
Open questions
Why dopamine blockers do little for low motivation, flat emotion and thinking problems is unclear. Cobenfy (2024) works through acetylcholine receptors instead, so dopamine is not the whole story.
▸Antipsychotic medications reduce psychosis in Schizophrenia and psychosisWell replicated
The connection
Antipsychotics are the main medical treatment for schizophrenia. They reduce 'positive' symptoms such as hallucinations and delusions within days to weeks, and staying on them lowers relapse risk. They help much less with 'negative' symptoms, such as low motivation and flat emotion, or with problems in memory and concentration.
Who showed it and when
First seen in 1952 at Sainte-Anne Hospital in Paris, where Jean Delay and Pierre Deniker gave chlorpromazine to patients with psychosis.
The evidence
Stefan Leucht's 2012 meta-analysis of maintenance trials: about 27 percent relapsed within a year on medication versus about 64 percent on placebo.
Open questions
Roughly a third of patients respond poorly; whether everyone needs long-term medication, or some can taper safely after recovery, is actively studied.
▸Antipsychotic medications transformed Psychiatric medicine: drugs and brain treatmentsWell replicated
The connection
Chlorpromazine was the first drug that reliably reduced psychosis, launching modern psychopharmacology. Together with policy changes, it helped empty overcrowded state hospitals and moved psychiatry from custodial care and drastic procedures such as lobotomy toward medication and outpatient treatment.
Who showed it and when
Chlorpromazine reached the US as Thorazine in 1954, when state mental hospitals held over half a million patients; the numbers fell steadily afterward.
The evidence
Hospital census records trace the timing, and controlled trials in the 1950s–60s, including a large 1964 NIMH study, confirmed the drugs worked.
Open questions
Historians debate how much deinstitutionalization owed to drugs versus Medicaid funding and civil-rights reforms, and how underfunded community care fed homelessness and imprisonment.
▸Lobotomy was replaced by Antipsychotic medicationsWell replicated
The connection
Lobotomy spread because overcrowded hospitals had few tools to calm severely ill patients. Chlorpromazine offered a far safer, reversible way to reduce agitation and psychosis. Within a few years of its arrival lobotomies fell sharply, and by the 1960s the operation was rare.
Who showed it and when
Chlorpromazine reached the US in 1954; Walter Freeman, lobotomy's leading promoter, kept operating until 1967.
The evidence
Hospital and surgical records show lobotomy numbers dropping in the mid-1950s as Thorazine use rose; historians such as Jack Pressman document the shift.
Open questions
Lobotomy was already drawing medical criticism before 1954, so historians debate how much drugs caused its decline versus speeding one already under way.