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| |  Zyprexa (Olanzapine) IntraMuscular Rapidly Controls Acute Agitation in Bipolar Mania INDIANAPOLIS, IN -- August 2, 2001 -- Data published in the August issue of the Journal of Clinical Psychopharmacology suggest that an intramuscular formulation of the atypical antipsychotic Zyprexa® (olanzapine) rapidly reduces acute agitation in patients with bipolar mania. At the same time, Zyprexa IntraMuscular (olanzapine for injection) was associated with a low risk of developing movement disorders known as extrapyramidal symptoms (EPS). Agitation is a well-recognized behavioral syndrome with a range of symptoms, including hostility, extreme excitement, poor impulse control, tension, and uncooperativeness. Patients experiencing agitation in its severe forms are usually in an emergency situation and require immediate treatment to alleviate personal distress and to prevent harm to themselves and others. To date in the United States, there are no drugs, either in an oral or intramuscular formulation, specifically approved by the Food and Drug Administration for the treatment of acute agitation in patients with bipolar mania. In the absence of approved therapy, physicians routinely use older, typical antipsychotics and benzodiazepines. "Benzodiazepines can occasionally exacerbate agitation in certain bipolar patients, including the elderly and those who have experienced head trauma," said Dr. Karena Meehan, the study's primary author and global clinical research physician at Eli Lilly and Company. "Furthermore, typical antipsychotics can be associated with such EPS-related side effects as acute dystonia." In light of this, Dr. Meehan added, "there is an unmet need in the treatment of patients experiencing acute agitation." The patient population in this single agitation study included adults (men and women at least 18 years of age) who were diagnosed with DSM-IV bipolar disorder, manic or mixed. Patients were deemed by site physicians to have agitation severe enough to be appropriate candidates to receive injections if they had: a minimum total score of 14 on the five-item Positive and Negative Symptom Scale Excited Component (PANSS-EC); and at least one individual score of at least four on a one-seven scale, immediately prior to randomization. After a screening period, 201 patients were randomly allocated to treatment with either the atypical antipsychotic Zyprexa Intramuscular, intramuscular lorazepam, or intramuscular placebo. Patients received from one to three intramuscular injections based on the clinical judgment of the investigator: Zyprexa (10 mg, first two injections; 5 mg, third injection); lorazepam (2 mg, first two injections; 1 mg, third injection); or placebo (placebo, first two injections; Zyprexa 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first two hours, and at four-, six- and 24-hour post first injection using the PANSS-EC, the Agitated Behavior Scale (ABS) and the Agitation-Calmness Evaluation Scale (ACES). Extrapyramidal symptoms (EPS) were assessed by the Simpson-Angus (S-A) total score and the Barnes Akathisia Global (Barnes) score. At two-hours post first injection, Zyprexa IntraMuscular-treated patients showed a significantly greater reduction in scores on all agitation scales compared to patients treated with intramuscular lorazepam or intramuscular placebo. At 24-hours post first injection, Zyprexa IntraMuscular remained significantly superior to placebo in reducing agitation in acutely manic patients. Specifically, the study found: · Zyprexa IntraMuscular-treated patients had a significantly greater improvement based on the PANSS-EC than intramuscular placebo-treated and intramuscular lorazepam-treated patients, at 30, 60, 90 and 120 minutes post first injection (p less than .01 versus placebo and intramuscular lorazepam at all timepoints). · At the two-hour post first injection timepoint, Zyprexa IntraMuscular-treated patients had significantly greater mean improvement in the ABS (placebo, p less than .001; lorazepam, p=.0006) and the ACES versus intramuscular placebo and intramuscular lorazepam (p less than .01 for all comparisons). · The mean score on the ACES at endpoint for Zyprexa-treated patients was 5.14 (five=mild calmness), 4.22 (four=normal) for lorazepam-treated patients, and 3.08 (three=mild agitation) for placebo-treated patients. ·At the 24-hour post first injection timepoint, Zyprexa IntraMuscular-treated patients continued to show significantly greater improvement compared to intramuscular placebo on the PANSS-EC (p less than .05), ABS (less than .01) and ACES (p less than .01). "The rapid onset of action of Zyprexa IntraMuscular suggests promise for this treatment option," said Dr. Meehan. "For acutely agitated patients, the primary objective of treatment is to calm the patient as quickly as possible without causing excessive sedation." After the acute situation has been treated, the patient can be switched over to an oral formulation of the same drug for long-term treatment if clinically indicated. On February 14th, the U.S. Food and Drug Administration's Psychopharmacologic Drugs Advisory Committee unanimously recommended approval of an intramuscular formulation of Zyprexa for the control of agitation associated with dementia, schizophrenia and bipolar mania. The committee's recommendation was based upon the positive results from the clinical trials. Four clinical trials were conducted in agitated patients from three distinct disease states: two in schizophrenia, one in dementia and one in bipolar mania. In this single agitation study, no significant differences among the three treatment groups were observed in treatment-emergent EPS, acute dystonia or QTc interval changes. Treatment-emergent adverse events associated with Zyprexa IntraMuscular included dizziness, somnolence and asthenia, none of which differed significantly among the three treatment groups. In addition, clinically manageable decreases in blood pressures and/or heart rate were observed in some Zyprexa IntraMuscular-treated patients.
SOURCE: Lilly
Related Links: Zyprexa (olanzapine) and Eli Lilly and Company.
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