Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Olanzapine is a potential new "atypical" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.
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PMID:Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. 2654 64

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, dosage and administration, and cost of olanzapine are reviewed. Olanzapine is a serotonin-dopamine-receptor antagonist indicated for use in the treatment of schizophrenia and other psychotic disorders. The affinity of olanzapine for neuroreceptors is similar to that of clozapine. The drug is well absorbed from the GI tract; food has no effect. Olanzapine is more effective than placebo and equal to haloperidol in reducing psychotic symptoms on two rating scales. However, unlike typical dopamine-receptor antagonists used for antipsychotic therapy, olanzapine is more effective in reducing the negative symptoms of schizophrenia. The most frequent adverse drug reactions (ADRs) associated with olanzapine are somnolence, agitation, insomnia, and headache. Constipation and dry mouth occur as dose-dependent ADRs. Unlike clozapine, olanzapine does not cause agranulocytosis. No cases of tardive dyskinesia or neuroleptic malignant syndrome have been reported. Olanzapine has been associated with slight increases in hepatic transaminases. More study is needed to determine whether olanzapine interacts significantly with other drugs. The recommended starting dosage is 5-10 mg orally once daily. Efficacy beyond six weeks has not been evaluated; patients treated for longer than six weeks should be periodically reassessed. Olanzapine costs about 10 times more than typical antipsychotics because a generic version is not available; however, olanzapine costs less than clozapine therapy and may cost less than haloperidol in terms of total health care costs. Olanzapine offers an effective alternative for treating schizophrenia and has a favorable adverse-effect profile.
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PMID:Olanzapine: a serotonin-dopamine-receptor antagonist for antipsychotic therapy. 1047 99

Olanzapine's structural similarities to clozapine and the results of premarketing clinical trials suggested potential usefulness in treating patients with treatment-refractory psychoses. Sixteen inpatients from the state hospital with severe, refractory schizophrenic or schizoaffective psychoses received olanzapine in a prospective, 12-week, open-label trial. The olanzapine dose was 10 mg/day for at least the first 6 weeks and never exceeded 20 mg/day. Mood stabilizers and other antipsychotic agents were discontinued before olanzapine was started. Patients frequently became more agitated within the first several weeks of initiating treatment, requiring the increased use of benzodiazepines and often leading to the discontinuation of olanzapine. Two patients improved significantly. Overall, significant clinical improvement was noted only for motor side effects. This study concluded that olanzapine was not effective in this heterogeneous group with chronic, severe, treatment-resistant psychosis when used in this manner. Further research is needed to explain the tendency toward agitation upon transition to olanzapine, which is reminiscent of reported risperidone complications. Clinicians should be alert for this complication and should minimize concomitant medication changes that might add to the risk of emergent agitation.
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PMID:An open trial of olanzapine in patients with treatment-refractory psychoses. 993 45

Olanzapine, a new atypical antipsychotic drug, has been prescribed in the treatment of schizophrenia and psychotic mood disorders for approximately 2.3 million patients worldwide. Considering the increase in olanzapine prescriptions and the increased risk of suicide in this patient population, the number of reported cases of olanzapine overdose may be expected to increase. This report describes the clinical course and serum concentrations in a patient who consumed an olanzapine overdose (800 mg). Profound central nervous system depression and tachycardia without arrhythmia occurred within 2 hours after the ingestion. Additional clinical findings (ie, fever, mutism, agitation, dystonia, akathisia, elevated creatine kinase, and increased leukocyte count) were similar to those of neuroleptic malignant syndrome. After intubation, gut decontamination, and supportive care, the patient recovered and was discharged.
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PMID:Olanzapine overdose with serum concentrations. 1042 35

Two females with severe anorexia nervosa were treated with olanzapine in open trials. Olanzapine was tried because it has caused weight gain in other patient groups. Both anorexic patients had a chronic illness and had failed multiple other treatments. Olanzapine administration was associated with weight gain and maintenance as well as reduced agitation and resistance to treatment. These case histories support further exploration of this class of drugs in anorexia nervosa.
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PMID:Case reports of olanzapine treatment of anorexia nervosa. 1069 25

Acute, high-dose loading strategies (rapid neuroleptization) with the first-generation antipsychotics administered orally or parenterally, alone or combined with benzodiazepines, have been a commonly used treatment paradigm for controlling acutely agitated psychotic patients. The rationale was to achieve high plasma levels of drug within a shorter time period, resulting in rapid symptom mitigation. However, studies have shown that rapid neuroleptization with first-generation antipsychotics is associated with a greater incidence of side effects. To our knowledge, loading strategies with second-generation antipsychotics have not been investigated, primarily owing to a need for dose titration. Olanzapine, a second-generation antipsychotic, is well tolerated in doses ranging from 5 to 20 mg. The objective of this report was to determine experience with the use of up to 20 mg of an oral loading dose of olanzapine administered within 4 hours in the treatment of patients early in an acute psychotic phase of their illness. In the reported case series of 57 patients, olanzapine initiated at 15 to 20 mg/day was a safe and effective medication for rapidly calming the agitation of acutely agitated psychotic patients (rapid tranquilization). Furthermore, dose reduction over 2 to 3 weeks was achieved in a number of patients without appreciable loss of efficacy.
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PMID:Rapid tranquilization with olanzapine in acute psychosis: a case series. 1123 45

Although the more recently introduced antipsychotic drugs are increasing in popularity, the pattern of symptomatology when taken in overdose is not well defined. We monitored all enquiries to the National Poisons Information Service, London (NPIS, London) concerning antipsychotic drugs over a 9-month period in 1997 and report our findings concerning four drugs (olanzapine, clozapine, risperidone and sulpiride). All overdoses involving a single agent were followed up by a letter to the enquirer requesting details and outcome of the case. Although a total of 574 enquiries involving the selected antipsychotic drugs were received, only 45 of these cases involved overdose with a single agent. There were no fatalities or cases of convulsions in the series. Cardiac arrhythmias were only noted with sulpiride. Symptoms were most marked with clozapine, with a majority of patients experiencing agitation, dystonia, central nervous system (CNS) depression and tachycardia. Olanzapine and sulpiride produced a range of different symptoms, while most patients who had taken risperidone were asymptomatic. Monitoring poisons centre enquiries is a useful way of comparing overdose toxicities. We conclude that at least two of the novel antipsychotic agents, olanzapine and risperidone, appear to have a favourable overdose profile, which suggests that they are safer in overdose than the phenothiazines and butyrophenones.
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PMID:Overdose profiles of new antipsychotic agents. 1134 78

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 safety and efficacy of i.m. ziprasidone and olanzapine for treating acute agitation in patients with schizophrenia are described, along with factors to consider when evaluating the cost-effectiveness of these agents. Agitation is defined as excessive motor and verbal activity. Acute agitation has traditionally been treated with the combination of haloperidol 5 mg and lorazepam 2 mg i.m. Controlled trials have shown, however, that combination therapy of haloperidol or droperidol plus lorazepam i.m. is better than single-drug treatment at one hour but not earlier. Phase II and III clinical trials showed that both i.m. ziprasidone mesylate 10 mg and 20 mg and olanzapine 2.5 mg-10 mg controlled agitation faster in patients with schizophrenia than p.o. ziprasidone 2 mg and placebo. In addition, i.m. olanzapine 10 mg controlled agitation faster in patients with schizophrenia faster than haloperidol in 15 minutes. Olanzapine i.m. was also superior to placebo in patients with dementia and in patients with bipolar disorder with and without psychotic symptoms, suggesting that agitation may be a syndrome that is similar across a multitude of disease states. Dystonic reactions occurred in 2.6% of patients taking ziprasidone, compared with 9.2% of patients taking haloperidol. No patients receiving olanzapine experienced a dystonic reaction. Ziprasidone has been associated with prolonged QTc Intervals. Pharmaco-economic evaluations should include costs associated with repeat i.m. injections for agitated patients, increased time in the emergency room, case of switching from i.m. to oral therapy, adverse effects, and relapse, as well as medication costs. I.m. olanzapine and ziprasidone show promise for treating acute agitation in patients with schizophrenia, especially because of their safer adverse effect profile and faster onset of effectiveness compared with haloperidol.
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PMID:Continuum of care: stabilizing the acutely agitated patient. 1222 82

Parkinson's disease is a neuropsychiatric disease with multiple psychic disorders. They mainly result from a combination between neuropathogical lesions and antiparkinsonian drugs. The most frequent psychic disorders are depression and psychosis. So far, pharmacological treatments of depression has been poorly evaluated. It is suggested that the first-line treatment of depression in Parkinson's disease is the class of the Selective Serotonin Reuptake Inhibitors. The occurrence of worsening in parkinsonism and agitation in rare cases necessitates a meticulous clinical follow-up. The treatment of psychosis is based on the reduction of antiparkinsonian medications, by tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. When psychosis persists despite a simple levodopa monotherapy, then an antipsychotic drug is added. Clozapine is the only officially approved drug for psychosis in Parkinson's disease. Two double blind studies showed a clear antipsychotic effect without worsening of parkinsonism. Quetiapine, another atypical neuroleptic drug without risk of blood dyscrasia may prove to be as effective than clozapine. Olanzapine and risperidone can aggravate parkinsonism and should be used only as a last resort. Future studies will precise the place of anticholinesterases in the treatment of psychosis associated with dementia.
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PMID:[Psychic disorders] 1269 Mar 23


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