Thorazine

Marketed under the trade name Thorazine by Smith-Kline & French, chlorpromazine received Food & Drug Administration approval for psychiatric treatment in 1954. Recognized as the first antipsychotic drug, chlorpromazine played a prominent role in the deinstitutionalization movement--a federal policy responsible for the release of thousands of mentally ill patients from U.S. asylums during the 1960s and 1970s.

Chlorpromazine's origins are found in a series of phenothiazine amines noted for their antihistaminic properties. Researchers discovered that one of the most potent phenothiazine amines, promethazine--synthesized in France in the 1940s by the pharmaceutical firm Rhne-Poulenc--had major central nervous system side effects. Out of this discovery, Rhne-Poulenc researchers synthesized chlorpromazine, which not only had antihistamine and antiemetic properties but also made the effects of barbiturates more powerful.

It was the barbiturate-enhancing effect of chlorpromazine that led French naval surgeon Henri Laborit to it in 1951. Laborit was in search of a surgical anesthetic but discovered that chlorpromazine put his patients in a detached vegetative state. By 1952, Smith-Kline & French had purchased the rights to the drug from Rhne-Poulenc, and French psychiatrists Jean Delay and Pierre Deniker were touting the therapeutic effects that chlorpromazine had on schizophrenic patients.

Considering treatments for schizophrenia at the time, it is no surprise chlorpromazine was seen as a promising alternative. In the 1940s and early '50s, treatment of psychotic patients included lobotomy, electroshock, or insulin coma therapy. Intended to quell hallucinations and aggressive outbursts in patients, all three treatments were unreliable and offered irreversibly damaging side effects. The easily administered drug was a profound shift away from invasive procedures like the lobotomy.

After its introduction in the U.S. in 1954, chlorpromazine quickly rose to become a staple of asylum medicine. Cash-strapped and overcrowded state hospitals flocked to the cost-effective treatment, but it would not take long for chlorpromazine to extend beyond asylum medicine and be used as a treatment to return mental patients to society.

Likened to prisons and seen as a financial burden, state hospitals had fallen out of favor in the U.S.; small community care centers were viewed as the future of mental health care. With reports of chlorpromazine sending schizophrenic hallucinations and delusions into remission, the drug was now seen as a way for the federal government to realize a vision popularly known as the deinstitutionalization movement.

In a 1963 New York Times article titled "President Seeks Funds To Reduce Mental Illness," President John F. Kennedy argued that the new drugs and knowledge made it "possible for most of the mentally ill to be successfully and quickly treated in their own communities and returned to a useful place in society."

Consequent changes to the U.S. mental health system were dramatic. Mental hospital populations, at a high of 560,000 in 1953, dropped to 193,000 by 1975. Unfortunately, these figures do not represent the successful treatment and rehabilitation of schizophrenic patients. The hope that was placed in chlorpromazine's ability to treat schizophrenia was dimmed by evidence of serious side effects.

Of chlorpromazine's side effects, the most visible is tardive dyskinesia. Causing abnormal and purposeless movements, tardive dyskinesia's traits are similar to those found in Parkinson's disease. Early indications that the drug caused Parkinsonian-like symptoms were overshadowed by chlorpromazine's benefits, but by the 1970s, tardive dyskinesia had drawn enough attention to tarnish the drug's reputation and diminish its use.

Research into the effects of chlorpromazine has revealed that the drug blocks D2 dopamine receptors in the brain. This research has provided psychiatry with new antipsychotics that target schizophrenia and produce fewer side effects. Though still in use today, chlorpromazine is administered at much smaller doses. New antipsychotic drugs, such as clozapine, risperidone, olanzapine, and quetiapine, are currently favored over chlorpromazine.

Chlorpromazine Hydrochloride

Name: 2-Chloro-N,N-dimethyl-10H-phenothiazine-10-propanamine hydrochloride

CAS Registry: 69-09-0

Other names: Hibanil, Hibernal, Klorpromex, Largactil, Largaktyl, Megaphen, Promacid, Chloractil, Chlorazin, Sonazine, Marazine, Propaphenin, Taroctyl, Thorazine, Torazina, Promapar

Did you know that the sedative effect of Thorazine is so similar to a surgical lobotomy that the drug has been controversially labeled a "chemical lobotomy"?