To describe the safety of olanzapine treatment in adolescents (aged 13-17 years) with schizophrenia or bipolar I disorder, and to compare these data with those of olanzapine-treated adults.
Placebo-controlled database, adolescents: acute phase of 2 double-blind, placebo-controlled trials (3-6 weeks; olanzapine, N = 179, mean age = 15.5 years; placebo, N = 89, mean age = 15.7 years); overall adolescent olanzapine exposure database, adolescents: 4 trials (e.g., the 2 aforementioned studies, each with a 26-week open-label extension phase, and 2 open-label, 4.5- and 24-week trials; N = 454, mean age = 15.9 years); and adult database: 84 clinical trials of up to 32 weeks.
The mean daily dosage of olanzapine was 10.6 mg/day (exposure = 48,946 patient days). In the overall adolescent olanzapine exposure database, the most common adverse events included increased weight (31.7%), somnolence (19.8%), and increased appetite (17.4%). In up to 32 weeks of treatment, when compared with adults, adolescents from the overall adolescent olanzapine exposure database gained statistically significantly more weight (7.4 kg vs. 3.2 kg, p < .001); statistically significantly more adolescents gained > or = 7% of their baseline weight (65.1% vs. 35.6%, p < .001). Adolescents experienced statistically significant within-group baseline-to-endpoint changes in fasting glucose (p < .001), total cholesterol (p = .002), triglycerides (p = .007), and alanine aminotransferase (p < .001). Two patients from the overall adolescent olanzapine exposure database (0.4%) attempted suicide; 13 (2.9%) had suicidal ideation. In the placebo-controlled database, adolescents had statistically significant baseline-to-endpoint increases in prolactin (11.4 micrograms/L, p < .001); 47.4% had high prolactin levels.
The types of adverse events in olanzapine-treated adolescents appear to be similar to those of adults. The magnitude and incidence of weight and prolactin changes were greater in adolescents.
clinicaltrials.gov Identifiers: NCT00051298, NCT00050206, and NCT00113594.
"Olanzapine has been shown to be effective for treating the symptoms of schizophrenia and bipolar disorder in adults and schizophrenia and acute manic or mixed episodes associated with bipolar disorder in adolescents [6-10]. There have been reports about the safety of olanzapine in the fetus and infant, with some cases reporting normal births without complications and others reporting adverse outcomes, such as differences in birth weight  and neural development . "
[Show abstract][Hide abstract] ABSTRACT: Olanzapine use has been reported during pregnancy and breastfeeding, but there are no controlled clinical trials assessing the safety of olanzapine exposure to infants and fetuses. The purpose of this report was to review and analyze prospective post-marketing cases of pregnancy and breastfeeding with olanzapine, in order to guide clinicians and women on the use of olanzapine therapy during pregnancy and/or breastfeeding.
A worldwide safety database maintained by Eli Lilly and Company was searched for all spontaneous-reported data regarding olanzapine use during pregnancy and/or breastfeeding. Cases reported prior to pregnancy outcome were considered to be prospective, and follow-up was pursued after the delivery date to assess outcome.
Outcome data were available for 610 prospectively identified pregnancies during which olanzapine was used. The majority of women had normal births (66%), although premature births were reported in 9.8% and perinatal conditions in 8% of the pregnancies. A total of 102 pregnancies reported olanzapine treatment during breastfeeding. In these infants, the most commonly reported adverse events were somnolence (3.9%), irritability (2%), tremor (2%), and insomnia (2%), although the majority of pregnancies reported no adverse events (82.3%).
The frequency of fetal outcomes in these prospectively identified pregnancies exposed to olanzapine did not differ from rates of outcomes reported in the general population. These data may be useful to help guide clinicians and women decide to continue, or discontinue, olanzapine therapy during pregnancy and/or breastfeeding, but should be considered within the limitations associated with spontaneously reported data. Women should notify their clinicians if they become pregnant or intend to become pregnant while being treated with olanzapine. Because of limited experience in humans, olanzapine should be used in pregnancy only when potential benefit justifies potential risk to the fetus. Olanzapine should only be considered during breastfeeding when the potential benefit justifies the potential risk to the infant.
"Antipsychotic medication is generally accepted as a critical piece of a comprehensive care approach for younger populations with schizophrenia [5-11]. Long-term safety and tolerability in pediatric patients with schizophrenia is of paramount concern for clinicians, given that long-term antipsychotic treatment is the standard of care. "
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. METHODS: This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children's Global Assessment Scale, adverse event (AE) monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. RESULTS: A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7%) subjects completed this study: 209 of the 279 subjects (75%) in the 6-month group and 55 of the 111 subjects (50%) in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs ([greater than or equal to]10% of subjects) were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs) were reported by 36 (9%) subjects. The AE profile in this study was qualitatively similar to those of other studies in adult subjects with schizophrenia and in other psychiatric studies of risperidone in pediatric populations. CONCLUSIONS: Risperidone maintenance treatment in adolescents over 6 to 12 months was well tolerated, consistent with related studies in this clinical population, and associated with continued efficacy. Trial registration Clinical trials.gov registration number: NCT00246285 http://clinicaltrials.gov/ct2/show/NCT00246285?term=NCT00246285&rank=1.
Child and Adolescent Psychiatry and Mental Health 06/2012; 6(1):23. DOI:10.1186/1753-2000-6-23
"Although not clinically significant, this finding was highly statistically significant (P < 0.001). Further, 3% of adolescents in the exposure database moved from normal or borderline glucose levels into the diabetic range.110 Increases in fasting glucose with olanzapine treatment ranging from 0.6 to 10 mg/dL have been reported in several other pediatric trials (Table 2).30,31,95 "
[Show abstract][Hide abstract] ABSTRACT: Severe and persistent mental illnesses in children and adolescents, such as early- onset schizophrenia spectrum (EOSS) disorders and pediatric bipolar disorder (pedBP), are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.
PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine's pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.
Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.
The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine-treated youth focused attention on the potential long-term risks of atypical antipsychotics in youth.
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