olanzapine and Autistic-Disorder

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

To study the efficacy and safety of olanzapine for the treatment of children with autism associated with disruptive behavior problems.. A prospective open-label trial was conducted on 40 male children (mean age 12.2 +/- 2.2 years, range 7-17 years) meeting Diagnostic Statistical Manual IV criteria for autism. After a washout period from previous medications (2-14 days), patients received olanzapine (5-10 mg/day) for a 13-week treatment period. The primary efficacy measures were Aberrant Behavior Checklist (ABC) and Clinical Global Impressions-Severity (CGI-S) done at baseline and end of treatment. At the beginning and end of treatment, patients underwent laboratory and physical investigations: ECG, chest X-ray, urinalysis, serum chemistry, blood glucose and lipid profile, hematology and hepatitis B serology.. Paired comparison of baseline and 13-week endpoint scores showed significant reductions in ABC subscale scores for irritability (p < 0.0001), lethargy (p < 0.0001), stereotyped behavior (p < 0.005), hyperactivity (p < 0.0001) and inappropriate speech (p < 0.005). Of 40 patients, 12 (30%) were considered as 'improved' on CGI-S scores compared to baseline, a statistically significant difference (p < 0.05). No liver enzyme elevation or any other serum biochemical changes resulted from treatment, which was not associated with significant body weight changes or any other treatment-emergent side effects.. The study shows that olanzapine treatment can be beneficial in alleviating some behavioral symptoms (irritability, hyperactivity/noncompliance and lethargy/withdrawal) associated with autism. The short period of this trial limits inferences about adverse effects such as body weight increase and tardive dyskinesia. Further long-term placebo-controlled studies of olanzapine are required.

Topics: Adolescent; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Child; Humans; Kuwait; Male; Mental Disorders; Olanzapine; Prospective Studies; Psychological Tests; Psychometrics

Atypical antipsychotics have been shown to improve disruptive and repetitive behaviors in pervasive developmental disorders (PDDs), but they require assessment of potential side effects. This is the first placebo-controlled trial of olanzapine in the treatment of children and adolescents with PDD. Eleven patients with a diagnosis of either autism, Asperger's syndrome, or PDD not otherwise specified (PDD-NOS) and aged 6-14 years were randomized into an 8-week double-blind, placebo-controlled, parallel treatment study with olanzapine. There was a significant linear trend x group interaction on the Clinical Global Impressions- Improvement (CGI-I) and 50% on olanzapine versus 20% on placebo were responders. Olanzapine was associated with significant weight gain (7.5 +/- 4.8 lbs vs. 1.5 +/- 1.5 lbs on placebo). Olanzapine may be a promising treatment for improving global functioning of PDDs, but the risk of significant weight gain remains a concern. Additional studies are needed to determine the efficacy and safety of olanzapine in the treatment of children with PDD.

Topics: Adolescent; Antipsychotic Agents; Asperger Syndrome; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Double-Blind Method; Female; Humans; Male; Olanzapine; Pilot Projects; Treatment Outcome; Weight Gain

Conventional neuroleptics ameliorate symptoms in children with autistic disorder; however, they are known to cause dyskinesias. Atypical neuroleptics, including olanzapine, may have less risk for dyskinesia, but their efficacy in autistic disorder is not established. This study was designed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a standard comparator treatment.. In a parallel groups design, 12 children with DSM-IV autistic disorder (mean age 7.8+/-2.1 years) were randomized to 6 weeks of open treatment with olanzapine or haloperidol. Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol. Outcome measures included the Clinical Global Impressions (CGI) and the Children's Psychiatric Rating Scale (CPRS).. Both groups had symptom reduction. Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item. Subjects showed improvement on the CPRS Autism Factor (F1,9 = 24.4, p = .0008). Side effects included drowsiness and weight gain.. The findings suggest that olanzapine is a promising treatment for children with autistic disorder. Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required.

Topics: Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Child, Preschool; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; Male; Olanzapine; Pilot Projects; Pirenzepine; Treatment Outcome

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.

Topics: Animals; Antipsychotic Agents; Autism Spectrum Disorder; Autistic Disorder; Behavior, Animal; Disease Models, Animal; Female; Humans; Male; Memory Disorders; Neurons; Olanzapine; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Social Behavior; Valproic Acid

Second generation antipsychotics (SGA) are used in children for the treatment of various psychiatric diseases, including pervasive developmental disorders. These drugs can cause metabolic effects as hyperglycemia and diabetes. A 16-year-old young-boy, diagnosed with autism, developed diabetes mellitus type 1 whilst he was on treatment with olanzapine (started 4 months before), clomipramine, valproic acid and lithium. The hypothesis of druginduced diabetes imposed olanzapine interruption and clozapine initiation. Insulin therapy was practiced, with progressive dosage reduction, until complete cessation of treatment after 13 months. Blood sugar and HbA1c levels remained stable for about a year and then increased again, requiring the introduction of metformin that improved glycemia. In children and adolescents assuming SGA serum glucose and lipid profile should always be assessed before therapy and then frequently monitored. Drug selection must consider family history and the individual risk. Molecule final choice remains equilibrium between efficacy and safety.

Topics: Adolescent; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Blood Glucose; Clomipramine; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Lithium; Male; Metformin; Olanzapine; Valproic Acid

Ischemic colitis is the most common subtype of intestinal ischemia usually resulting from vasospasm, vessel occlusion or mesenteric hypoperfusion. Neuroleptics have seldom been linked to ischemic colitis by blocking peripheral anticholinergic and antiserotonergic receptors inducing severe gastrointestinal paresis. We report a young patient with severe ischemic colitis requiring surgery due to necrosis of the bowel. After exclusion of other potential causes, olanzapine was admitted as the cause of ischemia. Clinicians should be aware of how to recognize and treat the potentially life-threatening effects of neuroleptics.

Topics: Adult; Anastomosis, Surgical; Autistic Disorder; Benzodiazepines; Colitis, Ischemic; Colonoscopy; Humans; Male; Olanzapine; Selective Serotonin Reuptake Inhibitors

The appropriateness of use of generic instead of brand-name medication remains unresolved and controversial in several areas of medicine. Some evidence suggestive of variations in bioavailability and clinical effectiveness between different formulations make policy decisions occasionally difficult. The use of generic olanzapine is a widely acceptable practice on the basis of quality, safety and efficacy data and has been adopted in several countries.. The case of a 14 year old boy with bipolar affective disorder, autism and intellectual disability who had brand-name to generic olanzapine switch associated with rapid deterioration of his mental state is described. This clinical change was not related to any physical illness or other medication adjustment and resolved as rapidly when generic olanzapine was switched back to the brand-name formulation.. Caution should be exercised when policy for switching from brand-name to generic psychotropic medications are made, especially when using medications off label, in extremes of age and in those patients with co-morbid complicating factors such as intellectual disability.

Topics: Adolescent; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Bipolar Disorder; Drugs, Generic; Humans; Intellectual Disability; Male; Olanzapine; Severity of Illness Index

Topics: Adult; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Humans; Hyponatremia; Male; Olanzapine; Polydipsia, Psychogenic

Children with autism often display difficult behaviors including tantrums, extreme irritability, and physical aggression. There is emerging evidence that olanzapine is useful in decreasing these disruptive behaviors. The most common adverse effects are weight gain and short-term sedation. On the other hand, olanzapine rarely causes rhabdomyolysis. We report a case with rhabdomyolysis in an autistic child just after 2 doses of olanzapine treatment. Initial creatine kinase value was 30,690 IU/L (range, 5-130 U/L), and rhabdomyolysis resolved with hydration and alkalinization over 7 days. Monitoring serum creatine kinase levels may be useful in pediatric cases after initiation of olanzapine treatment.

Topics: Adolescent; Autistic Disorder; Benzodiazepines; Creatine Kinase; Fluid Therapy; Follow-Up Studies; Humans; Male; Olanzapine; Rhabdomyolysis; Selective Serotonin Reuptake Inhibitors

Topics: Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Child; Humans; Male; Masturbation; Olanzapine; Sexual Dysfunction, Physiological

Risperidone appears to be effective in treating behavioral problems in children with autistic disorder. Although increased appetite, weight gain, and sedation are among the most common side effects, risperidone-induced enuresis is rarely reported.. We will present two cases with risperidone-induced enuresis, and discuss our findings in the context of current literature.. Two children aged 11 and 10 years, diagnosed with autism and mental retardation, have developed new-onset diurnal and nocturnal enuresis respectively on their first and second weeks of risperidone monotherapy (1.5 and 1 mg/day). They did not experience sedation, and their medical history and workup were unremarkable. As enuresis did not resolve spontaneously, we decided to substitute risperidone with olanzapine. Enuresis ceased rapidly after discontinuation of risperidone with no emergence when patients were treated with olanzapine 5 mg/day for a period of 6 months and 1 year, respectively.. Although the pathophysiology of antipsychotic-induced enuresis remains unclear, a number of mechanisms including alpha(1)-adrenergic blockade, dopamine blockade, and antimuscarinic effects has been proposed. Olanzapine has lower alpha(1)-adrenergic and dopaminergic blockade properties, thus changing risperidone to olanzapine may be an alternative modality in risperidone-induced enuresis when antipsychotic treatment is crucial. Clinicians should be more vigilant about screening for this side effect, especially in younger population with developmental disabilities.

Topics: Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Child; Diurnal Enuresis; Humans; Intellectual Disability; Male; Nocturnal Enuresis; Olanzapine; Receptors, Adrenergic, alpha-1; Receptors, Dopamine; Receptors, Muscarinic; Risperidone

The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a diagnosis of either autistic disorder or pervasive developmental disorder not otherwise specified. Psychometric measures included the Clinical Global Impression of Severity/Improvement, the Aberrant Behavior Checklist, and the TARGET (a checklist of five target symptoms). Communication skills were assessed during behavioral analysis of a playroom session. Safety measures included clinical chemistry variables, electrocardiography, the SimpsonAngus Neurological Rating Scale, the Barnes Akathisia Scale, and vital signs. Twenty-three children completed the study and showed significant improvement on three subscales of the Aberrant Behavior Checklist (Irritability, Hyperactivity, and Excessive Speech) and the TARGET. The final mean dose was 10.7 mg/day. Several aspects of communication were also improved after olanzapine treatment. However, only three children were considered responders in terms of the Clinical Global Impression of Severity/Improvement scores. The most important adverse events were weight gain, increased appetite, and loss of strength. Three children showed extrapyramidal symptoms that disappeared after the dose was lowered. Thus, while olanzapine was a relatively safe medication in children, its clinical relevance in children with pervasive developmental disorder may be limited.

Topics: Adolescent; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Child; Child Development Disorders, Pervasive; Communication Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychometrics; Severity of Illness Index

Topics: Adolescent; Adrenergic alpha-Antagonists; Autistic Disorder; Benzodiazepines; Drug Therapy, Combination; Humans; Male; Masturbation; Mianserin; Mirtazapine; Olanzapine; Pirenzepine; Remission Induction; Selective Serotonin Reuptake Inhibitors

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

Topics: Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Child; Child Behavior Disorders; Humans; Male; Olanzapine; Pirenzepine