[6] Common side effects include movement problems, sleepiness, dry mouth, low blood pressure upon standing, and increased weight.
[6] Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, neuroleptic malignant syndrome, severe lowering of the seizure threshold, and low white blood cell levels.
[6] Chlorpromazine is used in the treatment of both acute and chronic psychoses, including schizophrenia and the manic phase of bipolar disorder, as well as amphetamine-induced psychosis.
[14] A 2014 systematic review carried out by Cochrane included 55 trials that compared the effectiveness of chlorpromazine versus placebo for the treatment of schizophrenia.
The systematic review also highlighted the fact that the side effects of the drug were 'severe and debilitating', including sedation, considerable weight gain, a lowering of blood pressure, and an increased risk of acute movement disorders.
[16][17] Symptoms of delirium in hospitalized AIDS patients have been effectively treated with low doses of chlorpromazine.
[19][20] It is often, particularly as palliation, used in small doses to reduce nausea by opioid-treated cancer patients and to intensify and prolong the analgesia of the opioids as well.
[22] Chlorpromazine has been used as a hallucinogen antidote or "trip killer" to block the effects of serotonergic psychedelics like psilocybin, lysergic acid diethylamide (LSD), and mescaline.
For example, Miki et al. 1992 trialed daily doses of chlorpromazine, reversing chloroquine resistance in Plasmodium chabaudi isolates in mice.
[30] Tardive dyskinesia (involuntary, repetitive body movements) and akathisia (a feeling of inner restlessness and inability to stay still) are less commonly seen with chlorpromazine than they are with high potency typical antipsychotics such as haloperidol[31] or trifluoperazine, and some evidence suggests that, with conservative dosing, the incidence of such effects for chlorpromazine may be comparable to that of newer agents such as risperidone or olanzapine.
[5] Cotreatment with CYP1A2 inhibitors like ciprofloxacin, fluvoxamine or vemurafenib can reduce chlorpromazine clearance and hence increase exposure and potentially also adverse effects.
[5] It also reduces propranolol clearance and antagonizes the therapeutic effects of antidiabetic agents, levodopa (a Parkinson's medication.
[5] Monoamine oxidase inhibitors (MAOIs) and thiazide diuretics may also accentuate the orthostatic hypotension experienced by those receiving chlorpromazine treatment.
[51] In addition to influencing the neurotransmitters dopamine, serotonin, epinephrine, norepinephrine, and acetylcholine it has been reported that antipsychotic drugs could achieve glutamatergic effects.
By using the technique of functional neurochemical assay chlorpromazine and phenothiazine derivatives have been shown to have inhibitory effects on NMDA receptors that appeared to be mediated by action at the Zn site.
In 1947, it synthesized promethazine, a phenothiazine derivative, which was found to have more pronounced sedative and antihistaminic effects than earlier drugs.
[59]: 77 A year later, the French surgeon Pierre Huguenard used promethazine together with pethidine as part of a cocktail to induce relaxation and indifference in surgical patients.
Another surgeon, Henri Laborit, believed the compound stabilized the central nervous system by causing "artificial hibernation" and described this state as "sedation without narcosis".
Known colloquially as "Laborit's drug", chlorpromazine was released onto the market in 1953 by Rhône-Poulenc and given the trade name Largactil, derived from large "broad" and acti* "activity".
[7] Following on, Laborit considered whether chlorpromazine may have a role in managing patients with severe burns, Raynaud's phenomenon, or psychiatric disorders.
At the Villejuif Mental Hospital in November 1951, he and Montassut administered an intravenous dose to psychiatrist Cornelia Quarti, who was acting as a volunteer.
Psychiatrists were reluctant initially, but on 19 January 1952, it was administered (alongside pethidine, pentothal and ECT) to Jacques Lh., a 24-year-old manic patient, who responded dramatically; he was discharged after three weeks, having received 855 mg of the drug in total.
[7] Pierre Deniker had heard about Laborit's work from his brother-in-law, who was a surgeon, and ordered chlorpromazine for a clinical trial at the Sainte-Anne Hospital Center in Paris where he was chief of the men's service.
[7] Together with the hospital director Jean Delay, they published their first clinical trial in 1952, in which they treated thirty-eight psychotic patients with daily injections of chlorpromazine without the use of other sedating agents.
[61] The response was dramatic; treatment with chlorpromazine went beyond simple sedation, with patients showing improvements in thinking and emotional behaviour.
[7] Deniker then visited America, where the publication of their work alerted the American psychiatric community that the new treatment might represent a real breakthrough.
[63] By 1954, chlorpromazine was being used in the United States to treat schizophrenia, mania, psychomotor excitement, and other psychotic disorders.
[29] Thorazine was often depicted in Tom Wolfe's The Electric Kool-Aid Acid Test to abort bad trips on LSD.
Brand names include Thorazine, Largactil, Hibernal, and Megaphen (sold by Bayer in West-Germany since July 1953).
[69] Chlorpromazine has tentative benefit[clarification needed] in animals infected with Naegleria fowleri[70] and shows antifungal and antibacterial activity in vitro.