Category:Neuroleptics: Difference between revisions

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== 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"/>

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"/>

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== 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[[Clozapine]] was withdrawn from several markets after 1975, when a cluster of cases of [[agranulocytosis]] — a severe loss of white blood cells — in Finland was associated with eight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>

[[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>

== Members ==

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== 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.

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 ==

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