Category:Neuroleptics: Difference between revisions

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[[~~Haloperidol~~]]

'''Neuroleptics''' (commonly "antipsychotics") are a class of medicines used principally to treat psychosis broadly, as well as chronic psychotic disorders (e.g. [[schizophrenia]]), and bipolar disorder in both manic and depressive phases.<ref name="calabrese2005">Calabrese JR, Keck PE, Macfadden W, et al. (2005). A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. ''Am J Psychiatry'' 162(7):1351–60. PMID 15994719.</ref> The class is generally dated to the introduction of [[chlorpromazine]] into psychiatric practice in 1952, an event widely regarded as the start of the modern era of psychopharmacology.<ref name="ban2007">Ban TA (2007). Fifty years chlorpromazine: a historical perspective. ''Neuropsychiatr Dis Treat'' 3(4):495–500. PMID 19300578.</ref>

== Origins ==

Chlorpromazine was synthesized in 1950 by the French pharmaceutical company Rhône-Poulenc as the compound RP-4560, developed from the phenothiazine family that had earlier yielded antihistamines.<ref name="lopezmunoz2005">López-Muñoz F, Alamo C, Cuenca E, et al. (2005). History of the discovery and clinical introduction of chlorpromazine. ''Ann Clin Psychiatry'' 17(3):113–35.</ref> The surgeon Henri Laborit observed that it produced calmness without heavy sedation and suggested a psychiatric use. In 1952 the psychiatrists [[Jean Delay]] and [[Pierre Deniker]], working in Paris, published the first clinical reports of its use in psychotic patients.<ref name="lopezmunoz2005"/> The medicine was marketed in France as Largactil in 1952 and approved in the United States, as Thorazine, in 1954.<ref name="lopezmunoz2005"/>

Its introduction is widely held to have contributed to the deinstitutionalization movement of the 1950s through the 1970s, during which large numbers of long-term psychiatric inpatients were discharged; historians note that this shift had multiple social and policy causes alongside the arrival of the new medicines.<ref name="lopezmunoz2005"/>

== Terminology ==

These medicines have been known by several names. The earliest, "major tranquillizer", described their calming effect; "neuroleptic", from Greek roots meaning roughly "to take hold of the nerve", came into use in the 1950s and refers to their effect on the nervous system. The term "antipsychotic" became common in the 1960s.<ref name="lopezmunoz2005"/> The newer term names a presumed therapeutic target rather than an observed effect; it has been noted that this implies a disease-specific action, while the underlying dopamine hypothesis of psychosis remains a subject of ongoing scientific debate.<ref name="lyman2025">Lyman M, McCutcheon RA (2025). Antipsychotic drugs at 75: the past, present, and future of psychosis management. ''Br Med Bull'' 156(1):ldaf016.</ref> This wiki uses "neuroleptic" as its primary term.

== First- and second-generation neuroleptics ==

The medicines introduced from the 1950s onward — chlorpromazine, [[haloperidol]] and others — are described as '''first-generation''' (or "typical") neuroleptics. They are generally understood to act mainly as antagonists at the dopamine D<sub>2</sub> receptor, and this activity is thought to be related both to their effects and to their characteristic movement-related side effects; the account is a widely used model rather than a complete explanation.<ref name="lyman2025"/>

A '''second-generation''' (or "atypical") group followed, distinguished largely by a reportedly lower tendency to cause movement-related effects. [[Clozapine]], first introduced in Europe in 1971, is generally regarded as the first second-generation neuroleptic.<ref name="crilly2007">Crilly J (2007). The history of clozapine and its emergence in the US market: a review and analysis. ''Hist Psychiatry'' 18(1):39–60. PMID 17580753.</ref> The distinction between the two generations is widely used but has been described as imprecise, since the agents within each group differ considerably from one another.<ref name="lyman2025"/>

== Clozapine and blood monitoring ==

Clozapine was withdrawn from several markets after 1975, when a cluster of cases of [[agranulocytosis]] — a severe loss of white blood cells — in Finland was associated with eight deaths.<ref name="idanpaan1975">Idänpään-Heikkilä J, Alhava E, Olkinuora M, Palva I (1975). Clozapine and agranulocytosis. ''Lancet'' 2(7935):611. PMID 51442.</ref> On the basis of trial evidence indicating greater effectiveness in treatment-resistant schizophrenia, it was later reintroduced — approved in the United States in 1989 — under a system of mandatory blood-count monitoring that remains a condition of its use.<ref name="kane1988">Kane J, Honigfeld G, Singer J, Meltzer H (1988). Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. ''Arch Gen Psychiatry'' 45(9):789–96. PMID 3046553.</ref>

== Safety ==

Reported adverse effects differ between the two generations, and the figures in the literature are population estimates that vary between studies. First-generation neuroleptics have been associated with extrapyramidal effects — including parkinsonism, acute dystonia, akathisia, and the potentially persistent movement disorder tardive dyskinesia.<ref name="lyman2025"/> Second-generation agents have been reported to carry a lower risk of these effects, but have been more commonly associated with metabolic effects, including weight gain, raised blood glucose, and changes in blood lipids. Neuroleptic malignant syndrome is a rare reaction, described in the literature as potentially life-threatening, that has been associated with the class as a whole. Individual response and tolerability are reported to vary considerably between people.

== References ==

[[Category:MedCategory]]

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