Chlorpromazine / CPZ / Thorazine - what is it?
Chlorpromazine is a tricyclic aliphatic phenothiazine which acts by postsynaptic inhibition of dopamine receptors. Chlorpromazine has other peripheral and central nervous system effects, producing both alpha adrenergic stimulation and blocking histamine- and serotonin-mediated effects. Chlorpromazine is indicated for the therapy of acute and chronic psychosis and for nausea and intractable hiccups. Chlorpromazine was approved for use in the United States in 1957 and was formerly the most commonly prescribed antipsychotic medication, being the prototypic, standard neuroleptic agent against which other antipsychotic agents were tested. In recent years, chlorpromazine has been replaced in large part by the atypical antipsychotics, which have fewer extrapyramidal and hepatic side effects. Current indications include psychotic disorders, schizophrenia, nausea and vomiting, acute intermittent porphyria and intractable hiccups. Chlorpromazine is available in multiple generic forms as tablets of 10, 25, 50, 100 and 200 mg, as extended release capsules of 200 and 300 mg, and as syrup in various concentrations. Parenteral forms are also available. Chlorpromazine was formerly available under the brand names Thorazine and Largactil. The typical maintenance dose of chlorpromazine is 100 to 200 mg daily. Common side effects include drowsiness, dizziness, headache, blurred vision, dry mouth, constipation, tremor, restlessness, muscle spasms and weight gain.
Hepatotoxicity / Injury
Liver test abnormalities have been reported to occur in up to 40% of patients on long term therapy with chlorpromazine, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually self-limited and unaccompanied by symptoms, reversing even without discontinuation.
Chlorpromazine is also a well known cause of acute cholestatic liver injury. Numerous instances of clinically apparent acute liver injury due to chlorpromazine have been reported in the literature, which is estimated to occur in 1:500 persons exposed. Chlorpromazine was formerly the most common cause of drug induced liver injury in the United States, but with the decrease in its use, chlorpromazine associated jaundice is now rarely reported. The clinical presentation and course are well defined. The onset of jaundice is usually within 1 to 5 weeks, and the pattern of serum enzyme elevations is typically cholestatic or mixed (Case 1). Immunoallergic manifestations (fever, rash and eosinophilia) occur in some but not all cases, and these manifestations are usually mild and self-limited. Autoantibody formation is rare. Most importantly, chlorpromazine jaundice can be prolonged and associated with vanishing bile duct syndrome (Case 2).
Studies on the drug's effects:
"In early attempts to define the nature of drugs like chlorpromazine and reserpine, Delay and Deniker stressed two aspects of the drugs’ effects: the peculiar nature of the sedation, which, in contrast to barbiturates, produced a sleep from which people could be easily roused, and the state of disinterest produced by the drugs (Deniker, 1956; Delay & Deniker, 1956). They saw the motor effects as incidental rather than primary, but the sedation and indifference were also regarded as neurological effects by virtue of being induced by drug action on the brain and nervous system. In early papers, therefore, they referred to chlorpromazine as a “neuroplegic” drug (from the Greek to paralyze),2 and, in 1955, they replaced this term by the term “neuroleptic” (from the Greek to seize), still emphasizing the sedative and emotional effects of the drug, rather than its motor effects (Delay & Deniker, 1955)."
Published in 1957, along with 21 other cases: "A 26 year old woman with depression was started on chlorpromazine (75 mg/day) and developed generalized pruritus (severe itching of the skin) one week later followed by fever, nausea and dark urine. After 21 days of therapy, she was seen by her physician and chlorpromazine was stopped. There was no history of liver disease or alcohol abuse. She was jaundiced but afebrile (not feverish) and without rash. The liver was enlarged but nontender. "
An account from "David" a patient undergoing treatment for schizophrenia, prescribed CPZ noted: Largactil (CPZ's French name) which, although produces a queer sort of compulsion to do things, eliminates ambition, imagination, memory and intelligence. Nurses did not have a therapeutic role, and in the early 1960s they were not even allowed to look at the case-notes.
Uses:
- In 1952, chlorpromazine appeared on the psychiatric scene in Paris. It was more effective than any of the old drugs, including morphine and scopolamine (hyoscine) combinations, for controlling excitement and agitation, and it could relieve also psychotic symptoms, such as delusions and hallucinations. Although the psychiatric establishment received CPZ incredulously, for psychiatrists working on the front line it was a miracle drug. He (Paul Charpentier, France) found that CPZ, in the dosage of 50 to 100 mg given intravenously, produced disinterest without loss of consciousness and with only a slight tendency to sleep.
- In most patients CPZ alone, in the daily dosage of 75 mg, was sufficient for controlling behavior.
- 1964: David’s psychiatric career began after he was charged with stealing chocolate bars in a cinema. This minor misdemeanour was treated severely. He never appeared in court but was sent to a psychiatric unit for juveniles at the age of 16 in 1959. We assume he must have been behaving oddly. A year later he was in a mental hospital.
- 1970s: advertisements for many substances reflected the marketing advantages of a drug-centered model in aiming at a broad range of psychiatric situations.
- By the end of the 1970s, however, the industry appeared to have come into line with the professional view, and the drugs were mostly portrayed as specific treatments for schizophrenia with references to their drug-induced effects expunged.
- Possible recreational use, also called "Thorazine" today.
- Today (Thorazine) It can treat mental illness, behavioral disorders, tetanus, biopolar disorder, blood disorders such as porphyria, and severe nausea and vomiting. It can also reduce anxiety before surgery.
History / Timeline
- 1951: Chlorpromazine was synthesized in the laboratories of Rhône-Poiulenc.
- 1952: became available on prescription in France. Its effectiveness was reflected in the transformation of disturbed wards; its commercial success stimulated the development of other psychotropic drugs.
- Came to US in 1954 officially, but Winkelman noted that the drug was being trial in 1953 to two hundred psychiatric patients.
- Early 1960s: became popular for commercial use, treating schizophrenia in mental institutions. Both inpatient and outpatient.
- 1960s: became popular for recreational use as well
- 1970s: a drug-centered model in aiming at a broad range of psychiatric situations.
- By the end of the 1970s, the drugs were mostly portrayed as specific treatments for schizophrenia with references to their drug-induced effects expunged.
- 1980s, based on the success of CPZ, newer drugs were formulated and introduced.
- Today, CPZ is now referred to as "Thorazine", It can treat mental illness, behavioral disorders, tetanus, biopolar disorder, blood disorders such as porphyria, and severe nausea and vomiting. It can also reduce anxiety before surgery.
My own comments on the above and other things:
- I wonder if Woodlawn Jane Doe had liver damage from prolonged used? What levels were measured in her system?
- She could have been an outpatient at the time of her death, some patients could lead relatively healthy lives if they had a mental illness and was taking medications. The longer the use of CPZ, the longer the patient could last off of CPZ before relapse occurred.
- A young man named "David" referenced above was charged with stealing chocolate bars in a cinema. This minor misdemeanour was treated severely. He never appeared in court but was sent to a psychiatric unit for juveniles at the age of 16 in 1959. A year later he was in a mental hospital. Could this have happened to our Woodlawn JD?
- Could she have escaped from a juvenile psychiatric unit?
- Could she have been killed in a juvenile psychiatric unit and then dumped?
- Was she sent away to MD to a juvenile psychiatric unit? That would explain the lack of any missing persons report from the Boston area.
- Random note, but in the 1960s, Jamaica Plain High School had an agriculture course of study for 9th, 10th, 11th and 12th graders. They were allowed to work outside of school, go on field trips, etc. (From 1971 JP yearbook)
- Sheppard Prat is a psychiatric hospital located in Towson, a northern suburb of Baltimore. It has been operating for over 125 years. The 1970s, over 300 people had beds, all with a wide range of mental illnesses. They stayed there until they left or until their funding ran out. Sheppard Prat is located only 25 minutes from where Woodlawn JD was dumped.
- Justice Resource is another organization that has been helping rehabilitate youths ages 10 to 18 who have been charged with crimes since 1970. "Many of the kids who have come through the doors of Justice Resources -- which Harrison founded after coming to Baltimore in 1970 -- have been black, poor and fatherless like he was. Harrison has influence with some of them because he knows from years of personal experience what can befall children who were raised in those circumstances." Justice Resource is about 20 minutes away from where Woodlawn JD was found. JR was funded by the Department of Juvenile Services. In 2004, the DJS stopped by funding JR (1.2 million).
- Henry Phipps Psychiatric Clinic opened in 1913, regarded as "first of its kind". "Before the founding of the Phipps Psychiatric Clinic in Baltimore, Maryland, patients with severe mental disorders often went to Bellevue Hospital in New York City...HPPC record organization began in 1973, the existing records (that werent destroyed by Adolf Myers and his wife) moved from the Welch Library into storage in 1973." Where is this storage? Could it have documents pertaining to "Jasmine"?
That was super long, but I went down a few rabbit holes trying to find out why the drug CPZ was in Woodlawn JD's system.
