Eleven Years of Clozapine Experience in Autism Spectrum Disorder: Efficacy and Tolerance.

BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental disorders that comprise wide graduated clinical expressions but similar core symptoms (repetitive, stereotyped behavior, and social communication disabilities). Many patients with ASD have disruptive behaviors like aggressiveness, temper tantrums, or self-injury that interfere with their socializations, their learning abilities, and their quality of life. These behaviors represent a common target for pharmacology. Beherec et al (J Clin Psychopharmacol. 2011;31:341-344) (first cohort), showed the efficacy of clozapine on disruptive behaviors in 6 patients with autism who were older than 16 years. The aim of this study was to assess the efficacy and tolerance of clozapine in a new cohort and the long-term effect in our first cohort. PROCEDURES: Concerning the replication study, we conducted a retrospective study of the changes of aggressive behaviors for all patients with ASD who were treated with clozapine from 2011 to 2017. Disruptive behaviors were monitored from 1 to 6 months before and after the initiation of the clozapine. RESULTS: All the patients of the first cohort were still on clozapine after an average of 11 + 2.6 years, with the same efficacy and no serious adverse effect was noted. For the replication study, 13 patients were included. Clozapine resulted in a significant decrease in the number of the days with aggression (65.2% + 32.6%). Once again, no serious adverse effect was notified. All the patients had a better quality of life. CONCLUSIONS: Our study confirms that clozapine could be an efficacious and well-tolerated treatment for ASD patients with disruptive behaviors who do not respond to other antipsychotics on the long term.

Dementia in middle-aged patients with schizophrenia.

BACKGROUND: Although numerous studies have assessed cognitive dysfunction in patients with schizophrenia, very few have focused on the diagnosis of dementia. OBJECTIVE: Our objectives were to accurately diagnose dementia in a cohort of middle-aged patients with schizophrenia and to assess the type of dementia. METHODS: 96 patients with schizophrenia (46 inpatients and 50 outpatients), aged 50 to 70 years, underwent a psychiatric, neurological, and neuropsychological evaluation at baseline and after a 20-month follow-up. We established a 3-step procedure: 1) diagnose dementia according to the DSM-IV criteria, using the Mattis Dementia Rating and Activities of Daily Living scales; 2) characterize dementia using brain imaging, perfusion by 99mTc-ECD-SPECT and laboratory tests including Alzheimer's disease cerebrospinal fluid biomarkers; and 3) search for genetic determinants. RESULTS: Fourteen patients fulfilled the diagnostic criteria of dementia. Four were diagnosed with possible or probable behavioral-variant frontotemporal dementia (bvFTD), two with probable Alzheimer's disease, two with probable vascular dementia (including one due to CADASIL), one with CNS inflammatory disease, and six could not be fully characterized. CONCLUSIONS: The diagnosis of dementia in middle-aged patients with schizophrenia is challenging but possible, using a multistep procedure. The most frequent condition, bvFTD, could reflect the presence of an evolutive neurodegenerative process in some patients.

Retrospective review of clozapine in the treatment of patients with autism spectrum disorder and severe disruptive behaviors.

Autism spectrum disorder (ASD) is a serious childhood-onset disorder in which social and language development are primarily affected, with associated repetitive behavior and, in some patients, behavioral symptoms including aggression and self-injury. In ASD, risperidone and aripiprazole are the only second-generation antipsychotic drugs that have shown to decrease disruptive behaviors in large-scale, controlled, double-blind studies. However, in some patients, these medications are not effective. Clozapine, a second-generation antipsychotic drug known to be effective in the treatment of aggression associated with schizophrenia, has received little attention in ASD.We conducted a retrospective analysis of the changes in disruptive behaviors for all patients with ASD treated with clozapine from 2002 to 2010. Disruptive behaviors were monitored during the 4 to 6 months before and after the initiation of clozapine. Long-term tolerance (10 months to 7 years) was also assessed. The relationship between disruptive behaviors and period of treatment (before and after clozapine) was studied with a generalized linear marginal model. Clozapine resulted in a significant 2-fold decrease in the number of the days with aggression, a decrease in the number of psychotropic drugs, and a decrease in the dose of the antipsychotic drugs. The long-term tolerance of clozapine (white blood cell count and extrapyramidal effects) was good, with the exception of significant weight gain (14.3 ± 10.9 kg), the occurrence of metabolic syndrome in 1 patient, and tachycardia in another patient.These results suggest that clozapine should be considered for the management of disruptive behaviors in patients with ASD not improved by first-line antipsychotic drugs.