An international clozapine titration guideline to increase its safety and move forward on the route started by German-speaking psychiatrists in the 1960s

Leon, José de; Schoretsanitis, Georgios; Ruan, Changgeng; Cuevas, Carlos De las; Kane, John M.; Correll, Christoph U.

doi:10.1007/s00406-022-01407-7

Cited by 7 publications

(2 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The author cannot deny that a reasonable argument in favor of trusting the US recommendations for clozapine use is that the US is responsible for the resurrection of clozapine. Clozapine was introduced in German-speaking countries 3 and was almost "killed" by a letter to the editor 4 from Finland describing 8 patients who died from clozapine-induced agranulocytosis. Then, clozapine was resuscitated for a restricted use in treatment-resistant schizophrenia (TRS) by a US multicenter randomized clinical trial (RCT) published in 1988 5 that led to approval by the FDA in 1989 and the generalized worldwide use of clozapine for TRS.…”

Section: A Paradoxical Hypothesis: Major Standard Clozapine Reference...mentioning

confidence: 99%

See 1 more Smart Citation

Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing

León

2023

Psychiatry Investig

View full text Add to dashboard Cite

This review article argues against trusting standard clozapine references, including the US package insert, because they do not include advances in the sciences of pharmacokinetics and pharmacovigilance and ignore the effects of ethnic ancestry on therapeutic dosing. The minimum therapeutic dose leading to the minimum therapeutic concentration of 350 ng/mL in serum/plasma can be used to compare individuals/groups with treatment-resistant schizophrenia. The US clozapine package insert recommends targeting doses of 300-450 mg/day and, subsequently, increments of up to 100 mg with a maximum dose of 900 mg/day. Ethnic ancestry is defined by DNA ancestry group. Asians (people with ancestry ranging from Pakistan to Japan) and Indigenous Americans are similar in clozapine dosing; their average clozapine minimum therapeutic dose ranged from 166 mg/day (female non-smokers) to 270 mg/day (male smokers). For those with European ancestry, average clozapine minimum therapeutic doses ranged from 236 mg/day (female non-smokers) to 368 mg/day (male smokers). Based on limited studies, Black (African sub-Saharan ancestry) patients may be treated with typical US doses (300-600 mg/day), assuming no poor metabolism (PM) status. Ancestry's impact on clozapine lethality in four countries is discussed (two countries with highly homogenous populations, Denmark and Japan, and two countries with increasingly heterogenous populations due to immigration, Australia and the UK). An international guideline with 104 authors from 50 countries/regions was recently published, providing 6 personalized clozapine titration schedules for adult inpatients (3 ancestry groups and PM/non-PM schedules) and recommending c-reactive protein monitoring at baseline and weekly for 4 weeks.

show abstract

Section: A Paradoxical Hypothesis: Major Standard Clozapine Reference...mentioning

confidence: 99%

“…31 The international guideline is being translated into Chinese, Croatian, Korean, Japanese, Russian, and Spanish and being disseminated in summary articles in psychiatric journals of national distribution across multiple countries/regions. 3,21,31,70,76,100,141,[173][174][175]…”

Section: Update Of the International Titration Guidelinementioning

confidence: 99%