clozapine and Autistic-Disorder

Topics: Antipsychotic Agents; Autistic Disorder; Child; Child Behavior Disorders; Clozapine; Humans; Male; Psychotic Disorders; Treatment Outcome

Atypical antipsychotics are emerging as the first-line pharmacologic treatment for irritability (i.e., aggression, self-injurious behavior, and severe tantrums) in children and adolescents with autistic and other pervasive developmental disorders. Results from placebo-controlled and open-label studies of clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole in this subject population are reviewed. Additional placebo-controlled trials and studies of longer-term safety and tolerability are needed.

Topics: Adolescent; Aggression; Antipsychotic Agents; Aripiprazole; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Child, Preschool; Clozapine; Dibenzothiazepines; Disorders of Excessive Somnolence; Humans; Obesity; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

Autistic disorder and the group of related conditions defined as pervasive developmental disorders are chronic neurodevelopmental disorders starting in early childhood and affecting a significant number of children and families. Although the causes and much of the pathophysiology of the disorder remain unknown, in recent years a number of available medication treatments have been identified as holding promise in alleviating some of the most disabling maladaptive behaviors, associated with pervasive developmental disorders. However these treatments do not address the core symptoms of the disease and oftentimes their side effects outweigh their benefits. Therefore there is substantial need for new medications that are safer and more effective in addressing the behavior symptoms of autism. The aim of this review is to highlight the available current pharmacotherapies and those emerging treatments with potential to enhance the treatment options of patients with pervasive developmental disorders.

Topics: Antidepressive Agents; Antipsychotic Agents; Autistic Disorder; Clinical Trials as Topic; Clozapine; Humans; Placebos; Risperidone

Topics: Autistic Disorder; Child; Clozapine; Drug Administration Schedule; Female; Humans; Male; Psychiatric Status Rating Scales; Treatment Outcome

Oxytocin (OT) is critical for the expression of social behavior across a wide array of species; however, the role of this system in the encoding of socially relevant information is not well understood. In the present study, we show that chemogenetic activation of OT neurons within the paraventricular nucleus of the hypothalamus (PVH) of male mice (OT-Ires-Cre) enhanced social investigation during a social choice test, while chemogenetic inhibition of these neurons abolished typical social preferences. These data suggest that activation of the OT system is necessary to direct behavior preferentially toward social stimuli. To determine whether the presence of a social stimulus is sufficient to induce activation of PVH-OT neurons, we performed the first definitive recording of OT neurons in awake mice using two-photon calcium imaging. These recordings demonstrate that social stimuli activate PVH-OT neurons and that these neurons differentially encode social and nonsocial stimuli, suggesting that PVH-OT neurons may act to convey social salience of environmental stimuli. Finally, an attenuation of social salience is associated with social disorders, such as autism. We therefore also examined possible OT system dysfunction in a mouse model of autism,

Topics: Action Potentials; Animals; Appetitive Behavior; Autistic Disorder; Benzodiazepines; Calcium Signaling; Clozapine; Disease Models, Animal; Exploratory Behavior; Genes, Reporter; Male; Mice; Mice, Knockout; Microfilament Proteins; Nerve Tissue Proteins; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Patch-Clamp Techniques; Pyrazoles; Receptors, Oxytocin; Social Behavior; Wakefulness

Topics: Adolescent; Aggression; Antipsychotic Agents; Autistic Disorder; Clozapine; Female; Humans; Treatment Outcome

Topics: Adolescent; Aggression; Antipsychotic Agents; Autistic Disorder; Clozapine; Drug Administration Schedule; Humans; Male; Psychiatric Status Rating Scales; Treatment Outcome

Topics: Adult; Aggression; Autistic Disorder; Clozapine; Follow-Up Studies; Humans; Male; Psychiatric Status Rating Scales; Social Behavior

A case of neuroleptic malignant syndrome (NMS) in a 23 year old male patient is reported. The symptoms were hyperthermia, muscle rigidity, change in mental status, sinus tachycardia, creatinine phosphokinase elevation and myoglobinuria. The patient suffered from severe muscle pain and compromised respiratory function. Treatment was cessation of neuroleptic medication and institution of intensive medical care focusing on symptomatic treatment. One week after admission clinical status and laboratory findings were normalized and the patient was readmitted to a psychiatric hospital. The neuroleptic medication of the reported patient had been olanzapine during seven months at a dose of 25 mg daily. The day before onset of NMS the pharmacological treatment was supplemented by 100 mg of clozapine. The cause of onset of NMS in this case is discussed. Clozapine, an atypical neuroleptic, is known to have reduced potential to cause NMS and in such cases without extrapyramidal symptoms. Olanzapine, however, has not yet been reported to cause NMS. Alternatively the cause of onset of NMS in this patient could be explained by the combination treatment and possible synergistic effect of the two antipsychotic drugs. Further research in this field is needed.

Topics: Adult; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Clozapine; Drug Synergism; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine

A study of a 16.8-yr.-old female is presented to highlight aspects of Asperger's Syndrome as distinguished from cognate developmental and mood disorders. Brief therapy and pharmacological implications are mentioned.

Topics: Adolescent; Autistic Disorder; Bipolar Disorder; Clozapine; Combined Modality Therapy; Diagnosis, Differential; Female; Humans; Patient Admission; Psychotherapy; Residential Treatment

We report on a patient who became jaundiced during treatment with clozapine (Leponex). Histologically, cholestatic hepatitis with single-cell necroses of hepatocytes and infiltration of the portal zones with eosinophilic granulocytes were found. The patient recovered after discontinuation of clozapine, and liver function tests returned to normal within 4 weeks. This adverse effect of clozapine suggests that this "atypical" tricyclic neuroleptic resembles the phenothiazines both with regard to therapeutic spectrum and side effects.

Topics: Aged; Autistic Disorder; Cholestasis, Intrahepatic; Clozapine; Dibenzazepines; Female; Humans; Liver