Category:Neuroleptics: Difference between revisions

The neuroleptics, more widely known as the "antipsychotics", are the medicines used to treat psychosis, the disturbances of thought and perception that mark schizophrenia and the other psychotic illnesses, and used as well in the manic and the depressive phases of bipolar disorder.^[1] The class has a definite beginning. Chlorpromazine was synthesized in 1950 by the French company Rhône-Poulenc, the compound RP-4560, out of the phenothiazine family that had already given medicine its antihistamines; the surgeon Henri Laborit, using it to settle patients before operations, saw that it produced a striking calm without heavy sedation and pressed psychiatry to try it. In 1952, at hospitals in Paris, the psychiatrists Jean Delay and Pierre Deniker gave chlorpromazine to psychotic patients and published the first clinical reports of what it could do.^[2] Its arrival is generally taken as the start of modern psychopharmacology.^[3]

Chlorpromazine reached the French market in 1952 as Largactil and the United States in 1954 as Thorazine, and within a few years it had altered psychiatry's institutions as well as its prescriptions: its introduction is widely held to have helped make possible the deinstitutionalization of the following decades, when large numbers of long-stay psychiatric patients were discharged, though historians are clear that social and policy currents drove that shift alongside the medicine.^[2] The class has carried several names. The earliest, "major tranquilizer", described the calm; "neuroleptic", from Greek roots meaning roughly to take hold of the nerve, came into use in the 1950s; "antipsychotic" spread in the 1960s. The newest term is the most confident, naming a disease the medicine is supposed to act against, and it sits a little ahead of the science, for the dopamine hypothesis of psychosis on which it rests remains a matter of genuine debate.^[4]

The medicines of the first wave, chlorpromazine, haloperidol, and the others introduced from the 1950s, are now called the first-generation or typical neuroleptics. They are understood to work mainly by blocking the dopamine D2 receptor, an action tied both to their benefit and to their characteristic movement-related side effects.^[4] A second-generation or atypical group followed, set apart by a lower tendency to cause those movement effects; clozapine, introduced in Europe in 1971, is generally counted the first of them.^[5] The two-generation division is universally used and genuinely imprecise, since the agents within each group differ widely from one another.

Clozapine's own history is the cautionary tale of the class. It was withdrawn from several markets after 1975, when a cluster of cases of agranulocytosis, a dangerous collapse of the white blood cell count, was traced in Finland and linked to eight deaths.^[6] It returned only because it proved to work where others failed: a 1988 trial established its effectiveness in schizophrenia that had resisted other treatment, and it was approved again in the United States in 1989 under a system of mandatory blood-count monitoring that remains a condition of its use to this day.^[7]

The hazards of the neuroleptics divide, roughly, along the same line as the generations. The first-generation medicines are associated with extrapyramidal effects, parkinsonism, acute dystonia, akathisia, and the sometimes irreversible movement disorder tardive dyskinesia; the second-generation medicines carry less of that burden but more metabolic harm, weight gain, raised blood sugar, and disordered blood lipids.^[4] Neuroleptic malignant syndrome, a rare and potentially fatal reaction, shadows the class as a whole. This category collects the wiki's neuroleptic pages and groups them, as the field does, by generation.

The neuroleptics are grouped, as psychiatry groups them, into three generations, which mark the order in which they reached use and broadly track their side-effect profiles.

• First generation (typical): the medicines of the 1950s onward, dopamine D2 antagonists carrying the greatest burden of movement-related effects. chlorpromazine, fluphenazine, perphenazine, trifluoperazine, prochlorperazine, thioridazine, thiothixene, loxapine, molindone, haloperidol, droperidol, and pimozide.
• Second generation (atypical): fewer movement effects, more metabolic ones. clozapine, risperidone, paliperidone, olanzapine, quetiapine, ziprasidone, asenapine, iloperidone, lurasidone, and lumateperone.
• Third generation: the dopamine partial agonists, which modulate dopamine signaling rather than simply blocking it. aripiprazole, brexpiprazole, and cariprazine.

This category indexes the neuroleptics: the medicines whose defining use is the treatment of psychosis, grouped above by generation. The boundary is that action against psychosis, however the individual medicine achieves it.

Several neuroleptics are used well beyond psychosis, and are cross-indexed accordingly. Many of the second- and third-generation agents are central to the treatment of bipolar disorder, in mania and in depression alike; some, quetiapine among them, are used at low doses for sleep or for anxiety; and a few first-generation phenothiazines, prochlorperazine in particular, are used more often as antiemetics than as neuroleptics. Following the wiki's multi-membership convention, a medicine is indexed wherever its pharmacology and its uses warrant.

Each neuroleptic indexed here has its own page, built on the wiki's standard structure for a medicine: a history-first account, then pharmacology, indications, adverse effects, and interactions. The three generation subcategories named in the index above collect the members of each generation.

This is one of the wiki's MedCategory class-overview pages. It carries the MedCategory and MedCategoryFull marker tags; the second suppresses the member list that MediaWiki would otherwise generate automatically, leaving the curated index above as the only one the reader sees. The category sits beneath Medicines and beneath Pharmaceutical, the origin category for medicines that came into use through scientific discovery rather than traditional practice. The wiki uses "neuroleptic" as its primary name for the class.