Longitudinal changes in clozapine dose in patients with treatment-resistant schizophrenia: a 5-year retrospective cohort study. 2023

Masaru Tsukahara, and Ryuhei So, and Shinichiro Nakajima, and Kohei Kitagawa, and Masafumi Kodama, and Hiroyoshi Takeuchi
Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama.

This retrospective cohort study aimed to investigate the longitudinal changes in clozapine dose over a 5-year period in patients with treatment-resistant schizophrenia (TRS). Patients with TRS who were administered clozapine at a hospital between April 2012 and December 2016 and continued treatment with clozapine for at least 1 year were included. Clozapine doses were compared at the dose-fixation point, defined as when the same regimen of clozapine had been continued for 8 weeks or longer, and the post-dose-fixation phase, at 12, 36 and 60 months after clozapine initiation. We included 103 patients and found no significant differences in clozapine dose between the dose-fixation point and post-dose-fixation phase. Approximately half of the patients were categorized into an unchanged group at 12 months after clozapine initiation, whereas approximately 40% of patients were categorized into either the decreased or increased group at 60 months. Multivariable regression analysis revealed that the change in clozapine dose between the dose-fixation point and 60 months after clozapine initiation was negatively associated with clozapine dose at the dose-fixation point. On average, the clozapine dose was unchanged during long-term treatment in patients with TRS, although the dose was decreased or increased in approximately 40% of the patients.

UI MeSH Term Description Entries
D003024 Clozapine A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Clozaril,Leponex
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000090663 Schizophrenia, Treatment-Resistant A subset of schizophrenia with an inadequate response in target symptoms following treatment with two or more ANTIPSYCHOTICS. Refractory Schizophrenia,Treatment-Resistant Schizophrenia,Schizophrenia, Refractory,Schizophrenia, Treatment Resistant,Treatment Resistant Schizophrenia
D012189 Retrospective Studies Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. Retrospective Study,Studies, Retrospective,Study, Retrospective
D012559 Schizophrenia A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior. Dementia Praecox,Schizophrenic Disorders,Disorder, Schizophrenic,Disorders, Schizophrenic,Schizophrenias,Schizophrenic Disorder
D014150 Antipsychotic Agents Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. Antipsychotic,Antipsychotic Agent,Antipsychotic Drug,Antipsychotic Medication,Major Tranquilizer,Neuroleptic,Neuroleptic Agent,Neuroleptic Drug,Neuroleptics,Tranquilizing Agents, Major,Antipsychotic Drugs,Antipsychotic Effect,Antipsychotic Effects,Antipsychotics,Major Tranquilizers,Neuroleptic Agents,Neuroleptic Drugs,Tranquillizing Agents, Major,Agent, Antipsychotic,Agent, Neuroleptic,Drug, Antipsychotic,Drug, Neuroleptic,Effect, Antipsychotic,Major Tranquilizing Agents,Major Tranquillizing Agents,Medication, Antipsychotic,Tranquilizer, Major

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