Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600097 (Sedation)
 1,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Olanzapine is an "atypical" antipsychotic agent with a high affinity for serotonin 5HT2A/C, 5HT3, 5HT6, and dopamine D1, D2, D3, D4 receptors. Depressed patients with psychotic disorders frequently require treatment with concomitant antipsychotic and antidepressant medications. Imipramine pharmacokinetics serve as a marker for hepatic CYP2D6, CYP1A2, CYP3A activity. An open-label, three-way randomized crossover study was done to determine the safety, pharmacokinetics, and potential for a drug interaction between olanzapine (5 mg) and imipramine (75 mg). Each drug was administered alone and in combination. Nine healthy men, ages 32 to 54 years, enrolled in the study. Psychomotor performance capacities, plasma olanzapine, imipramine, desipramine concentrations, and clinical laboratory tests were measured. Pharmacokinetic variables, vital signs, subjective tests for liveliness, and psychomotor outcomes were analyzed using a two-way ANOVA. Olanzapine was safe. Sedation, postural hypotension, and minor vital sign alterations occurred during all treatments. On the liveliness questionnaire, patients generally reported poorer (less lively) scores with olanzapine alone or coadministered with imipramine versus baseline scores. These effects disappeared within 24 hours after administration. Olanzapine alone and in combination decreased motor-speed tasks (finger tapping and visual-arm random reach) compared with baseline or imipramine treatment. Peak 6-hour changes were statistically significant but clinical importance was only marginal. Olanzapine concentrations were < 19% greater than with imipramine. But olanzapine did not affect the kinetics of imipramine or desipramine and, therefore, did not show a metabolic drug interaction involving CYP2D6.
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PMID:Olanzapine: interaction study with imipramine. 950 89

This double-blind study investigated the efficacy and safety of rapid-acting intramuscular olanzapine in treating agitation associated with Alzheimer's disease and/or vascular dementia. At 2 h, olanzapine (5.0 mg, 2.5 mg) and lorazepam (1.0 mg) showed significant improvement over placebo on the PANSS Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES), and both 5.0 mg olanzapine and lorazepam showed superiority to placebo on the Cohen-Mansfield Agitation Inventory. At 24 h, both olanzapine groups maintained superiority over placebo on the PANSS-EC; lorazepam did not. Olanzapine (5.0 mg) and lorazepam improved ACES scores more than placebo. Simpson-Angus and Mini-Mental State Examination scores did not change significantly from baseline. Sedation (ACES > or =8), adverse events, and laboratory analytes were not significantly different from placebo for any treatment. No significant differences among treatment groups were seen in extrapyramidal symptoms or in corrected QT interval at either 2 h or 24 h, and no significant differences among treatment groups were seen in vital signs, including orthostasis. Intramuscular injection of olanzapine may therefore provide substantial benefit in rapidly treating inpatients with acute dementia-related agitation.
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PMID:Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. 1192 74

The aim of the present study was to evaluate the objective and subjective efficacy as well as tolerability of olanzapine in acute treatment of schizophrenia spectrum disorders under naturalistic non-selective conditions. Inpatients with schizophrenia spectrum disorders, consecutively admitted over an 18-month period, treated with olanzapine, were included. Diagnoses were made according to ICD-10 criteria based on repeated clinical assessments. Efficacy and tolerability of olanzapine were assessed at baseline and at the end of inpatient acute treatment including Positive and Negative Symptom Scale (PANSS), Clinical Global Impression, subjective assessments, UKU and biological investigations. One hundred and twenty non-selected patients who met ICD-10 criteria for schizophrenia (73%), schizophreniform disorder (14%) or schizoaffective disorder (13%) were treated with olanzapine 15.3+/-5.2 mg/day. Baseline severity (PANSS total mean score 102.2) was higher compared to various admittance studies (PANSS total mean score 86-90). In 32% of patients (n=38), olanzapine treatment was discontinued, mainly because of inefficacy for positive (89%, n=34) and/or negative (95%, n=36) symptoms and/or because of adverse events (37%, n=14). Response rates as improvement in PANSS total score (after > or =3 weeks of treatment) of > or =20%, 30% or 40% were 68%, 55% and 35%, respectively. Response rates in post-hoc defined treatment resistant patients were not significantly different from non-refractory patients. Sedation (26%) was the most common side-effect, followed by weight gain (22%). With regards to subjective efficacy, 30% of the patients were not satisfied with the efficacy of olanzapine, while only 6% of the patients reported a not satisfying subjective tolerability. According to duration of olanzapine treatment, the results for patients, who remained in hospital, revealed a faster increase of weight compared to admittance studies (7 kg in 14 weeks versus 7 kg in 38 weeks). Olanzapine has been found to be effective and tolerable, also under naturalistic acute treatment conditions. Compared to previous double-blind admittance studies, patients had a higher severity of illness at entry and a lower > or =40% PANSS total score response rate. By contrast to previous results, mean dose of olanzapine was similar for multiple- and first-episode patients, and weight gain was more severe. The results underline the need of Phase IV studies for the assessment of clinical antipsychotic efficacy and tolerability.
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PMID:Objective and subjective efficacy as well as tolerability of olanzapine in the acute treatment of 120 patients with schizophrenia spectrum disorders. 1292 Mar 85

Olanzapine is an atypical antipsychotic that, in addition to its use in adults, is now indicated for the treatment of schizophrenia, and manic or mixed episodes associated with bipolar I disorder in adolescents aged 13-17 years. In a randomized, double-blind, multicentre, 6-week trial in adolescents aged 13-17 years with schizophrenia, the least squares mean reduction from baseline to 6 weeks in the Brief Psychiatric Rating Scale for Children (BPRS-C) total score (primary endpoint) was significantly greater with olanzapine than with placebo. In a randomized, double-blind, multicentre, 3-week trial in adolescents, aged 13-17 years, with manic or mixed episodes associated with bipolar I disorder, the mean reduction from baseline to 3 weeks in the Adolescent Structured Young Mania Rating Scale (YMRS) total score (primary endpoint) was significantly greater with olanzapine than with placebo. In extensions of each of the pivotal placebo-controlled trials in schizophrenia and bipolar mania, open-label treatment with olanzapine for up to 26 weeks produced significant reductions from baseline to endpoint in BPRS-C and YMRS total scores, respectively. Oral olanzapine was generally well tolerated in adolescents with schizophrenia or bipolar mania. Sedation and weight gain were the most common adverse events in placebo-controlled trials. Extrapyramidal symptoms were reported by 10% of olanzapine recipients compared with 6% of placebo recipients. Olanzapine-treated adolescents were likely to experience greater increases in bodyweight, sedation, blood lipids, serum prolactin and liver transaminase levels than olanzapine-treated adults. Therefore, careful consideration of risk-benefit is recommended before using olanzapine in adolescents.
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PMID:Olanzapine: in adolescents with schizophrenia or bipolar I disorder. 2036 8