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Treatment History
Archaeologists have unearthed skulls with clearly visible drillings, some datable back to 5000 BC suggesting that trepanning was a common treatment for psychosis in ancient times.

Early 20th century treatments for severe and persisting psychosis were characterized by an emphasis on shocking the nervous system. Such therapies include insulin shock therapy, cardiazol shock therapy, and electroconvulsive therapy. Despite considerable risk of shock therapy, such treatment was considered highly efficacious in the treatment of psychosis including schizophrenia. The acceptance of such dangerous treatments led to more invasive medical interventions including the lobotomy. The lobotomy, a neurosurgical procedure in which the fibres connecting the frontal lobe to the rest of the brain were severed, became a widely accepted practice, often performed in non-sterile environments such as small outpatient clinics and patient homes. Psychosurgery remained standard practice until the discovery of antipsychotic pharmacology in the 1950's.

The first clinical trial of antipsychotics (also commonly known as neuroleptics) for the treatment of psychosis took place in 1952. Chlorpromazine (brand name: Thorazine) passed clinical trials and became the first antipsychotic medication approved for the treatment of both acute and chronic psychosis. Although the mechanism of action was not discovered until 1963, the administration of chlorpromazine marked the advent of the dopamine antagonist, or first generation antipsychotic. Although first generation antipsychotics are highly efficacious in the treatment of both acute psychosis and disorders with psychotic features, the side-effects are particularly harsh, including high rates of often irreversible Parkinsonian symptoms such as tardive dyskinesia. With the advent of atypical antipsychotics (also known as second generation antipsychotics) came a dopamine antagonist with a comperable response rate but a far different side-effect profile including a lower risk of Parkinsonian symptoms but a higher risk of cardiovascular disease. Atypical antipsychotics remain the first-line treatment for psychosis associated with various psychiatric and neurological disorders including schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, dementia, and some autism spectrum disorders.