Efficacy of clozapine on dopamine supersensitivity psychosis in schizophrenia. 2017

Yusuke Nakata, and Nobuhisa Kanahara, and Hiroshi Kimura, and Hiroyuki Watanabe, and Masaomi Iyo
aDepartment of Psychiatry, Graduate School of Medicine bDivision of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan cClinic for Psychiatry and Psychotherapy, Ludwig Maximilians University of Munich, Munich, Germany.

Although the effectiveness of clozapine (CLZ) for patients with treatment-resistant schizophrenia (TRS) has been well established, its active mechanism has not been completely clarified. Several clinical studies showed that neuroleptic-induced dopamine supersensitivity psychosis (DSP) could be involved in the etiology of TRS. We preliminarily explored the possible beneficial effect of CLZ for dopamine supersensitivity schizophrenia. The present study is a case series. We followed 15 patients with DSP for about 2.5 years from the introduction of CLZ and compared the prevalence of episodes (particularly, rebound psychosis, tolerance to antipsychotic effects, or tardive dyskinesia) between the period before and during CLZ treatment. Our observation over 2.5 years following the introduction of CLZ showed that 13 of the 15 DSP patients presented no further DSP episodes. One patient showed continued tardive dyskinesia, which had already existed in the preperiod, and the other patient presented with rebound psychosis that appeared immediately after discontinuation of CLZ. The results of the present study indicated that DSP in schizophrenic patients treated with general antipsychotics disappeared over the subsequent 2.5 years under CLZ treatment, suggesting that the agent ameliorates the dopamine supersensitivity state induced by previous antipsychotic treatment.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011605 Psychoses, Substance-Induced Psychotic organic mental disorders resulting from the toxic effect of drugs and chemicals or other harmful substance. Psychoses, Drug,Psychoses, Toxic,Substance-Induced Psychoses,Toxic Psychoses,Drug Psychoses,Psychoses, Substance Induced,Substance Induced Psychoses
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
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
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

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