clozapine and Autism-Spectrum-Disorder

Topics: Antipsychotic Agents; Autism Spectrum Disorder; Clozapine; Humans; Myocarditis; Schizophrenia

Catatonia is a severe clinical syndrome which has been increasingly reported in autism spectrum disorder (ASD). The prevalence of catatonia in ASD is unknown. Diagnosing catatonia in ASD is complicated by overlapping clinical features such as mutism, stereotypies, and echophenomena. Here, we present the clinical histories of two individuals with ASD and catatonia who were successfully treated with clozapine. We have reported on a novel potential treatment option for catatonia in ASD. Additional studies are needed to evaluate the safety, efficacy, and tolerability of clozapine for the treatment of catatonia in ASD.

Topics: Autism Spectrum Disorder; Catatonia; Clozapine; Humans; Stereotyped Behavior; Stereotypic Movement Disorder

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aggression; Antipsychotic Agents; Autism Spectrum Disorder; Clozapine; Female; Follow-Up Studies; Humans; Male; Outcome Assessment, Health Care; Retrospective Studies; Young Adult

The aim of this retrospective study is to examine the clinical outcomes and safety of clozapine in children and adolescents with schizophrenia or other psychotic disorders/autism spectrum disorder (ASD) or affective disorders.. The inpatient and outpatient files of all children and adolescents treated with clozapine over a period of 34 months (from October 2011 to July 2014) were reviewed. Demographic and clinical data were examined to describe clinical and metabolic findings, dosing, and tolerability of clozapine treatment in youth with schizophrenia, other psychotic disorders, ASD, or bipolar disorder.. The 37 pediatric patients included 26 patients with schizophrenia or other psychotic disorders, 7 patients with ASD complicated by schizophrenia or other psychotic disorders or affective disorders, and 4 patients with ASD only. In all groups (n = 37) there was a significant reduction (p < 0.001) in Brief Psychiatric Rating Scale (BPRS) points after clozapine treatment during the inpatient period (38.78 ± 27.75 days). In patients with schizophrenia or other psychotic disorders co-occurring with ASD or not (n = 31), there was a significant improvement in psychotic symptoms according to Positive and Negative Syndrome Scale (PANSS) total scores and subscores (p < 0.001). Of the 26 patients with schizophrenia or other psychotic disorders, 8 (30.8%) showed a positive response (>30% symptom reduction on BPRS). In patients with ASD complicated by schizophrenia or other psychotic disorders or bipolar disorders (n = 7), there was a significant reduction (p = 0.017) in BPRS scores after clozapine treatment. The discontinuation rate for clozapine was 10.8%, and the most frequently observed side effect was hypersalivation (54.1%). Neutropenia associated with clozapine was observed in only one patient (2.7%).. Clozapine seems to be effective and safe in children and adolescents with schizophrenia or other psychotic disorders co-occuring with ASD or not. There is a need for further studies for determining the efficacy of clozapine in children and adolescents with bipolar affective disorder or ASD.

Topics: Adolescent; Antipsychotic Agents; Autism Spectrum Disorder; Bipolar Disorder; Child; Clozapine; Female; Humans; Inpatients; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Schizophrenia; Treatment Outcome; Turkey

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Autism Spectrum Disorder; Clozapine; Drug Therapy, Combination; Humans; Male

Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. Pharmacological and genetic experiments show that anandamide mobilization and consequent activation of CB1 cannabinoid receptors are necessary and sufficient to express the rewarding properties of social interactions, assessed using a socially conditioned place preference test. We further show that oxytocin, a neuropeptide that reinforces parental and social bonding, drives anandamide mobilization in the NAc. Pharmacological blockade of oxytocin receptors stops this response, whereas chemogenetic, site-selective activation of oxytocin neurons in the paraventricular nucleus of the hypothalamus stimulates it. Genetic or pharmacological interruption of anandamide degradation offsets the effects of oxytocin receptor blockade on both social place preference and cFos expression in the NAc. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions.

Topics: Analysis of Variance; Animals; Arachidonic Acids; Autism Spectrum Disorder; Benzamides; Benzodiazepines; Camphanes; Carbamates; Clozapine; Cocaine; Endocannabinoids; Immunohistochemistry; Infusions, Intraventricular; Lipids; Male; Mice; Mice, Inbred C57BL; Nucleus Accumbens; Oxytocin; Piperazines; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Receptors, Cannabinoid; Reward; Signal Transduction; Social Behavior