Meehan, K. et al. Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology 26, 494-504

Lilly Research Laboratories, Eli Lilly, Indianapolis, Indiana, United States
Neuropsychopharmacology (Impact Factor: 7.05). 04/2002; 26(4):494-504. DOI: 10.1016/S0893-133X(01)00365-7
Source: PubMed


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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    • "These results are similar to those reported by other authors. For instance, Huber et al. (2008) found correlations between the CGI-S and the PANSS-EC scales of 0.83; Meehan et al. (2002) reported an r = -0.71 between the PANSS-EC and the ACES scales; Leucht et al. (2005) [40] reported coefficients of 0.56 and 0.73 between the PANSS-EC and CGI-S scales. Using the entire PANSS, Levine et al. (2008) found correlations of r = 0.61 to r = 0.73 between the same scales. "
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    ABSTRACT: Despite the wide use of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) in a clinical setting to assess agitated patients, a validation study to evaluate its psychometric properties was missing. Data from the observational NATURA study were used. This research describes trends in the use of treatments in patients with acute psychotic episodes and agitation seen in emergency departments. Exploratory principal component factor analysis was performed. Spearman's correlation and regression analyses (linear regression model) as well as equipercentile linking of Clinical Global Impression of Severity (CGI-S), Agitation and Calmness Evaluation Scale (ACES) and PANSS-EC items were conducted to examine the scale's diagnostic validity. Furthermore, reliability (Cronbach's alpha) and responsiveness were evaluated. Factor analysis resulted in one factor being retained according to eigenvalue ≥1. At admission, the PANSS-EC and CGI-S were found to be linearly related, with an average increase of 3.4 points (p < 0.001) on the PANSS-EC for each additional CGI-S point. The PANSS-EC and ACES were found to be linearly and inversely related, with an average decrease of 5.5 points (p < 0.001) on the PANSS-EC for each additional point. The equipercentile method shows the poor sensitivity of the ACES scale. Cronbach's alpha was 0.86 and effect size was 1.44. The factorial analyses confirm the unifactorial structure of the PANSS-EC subscale. The PANSS-EC showed a strong linear correlation with rating scales such as CGI-S and ACES. PANSS-EC has also shown an excellent capacity to detect real changes in agitated patients.
    Full-text · Article · Mar 2011 · Health and Quality of Life Outcomes
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    • "However, carefully-controlled clinical studies of atypicals versus typicals for emergency treatment are scarce, but a number of comprehensive literature reviews have concluded that the atypical APs are at least as effective and generally have better tolerability than the typical APs administered with or without benzodiazepines [3,22,23,30]. For example, in a double-blind comparison of olanzapine versus the benzodiazepine lorazepam for treatment of acute psychiatric episodes, olanzapine treatment was found equally effective and with a better tolerability profile, particularly with respect to the incidence of EPS [31,32]. "
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    ABSTRACT: Conventional antipsychotics augmented with benzodiazepines have been the standard acute treatment for psychiatric emergencies for more than 50 years. The inability of patients to give informed consent limits randomised, controlled studies. This observational study on immediate therapy for aggression and impulse control in acutely agitated patients (IMPULSE) evaluated the short-term effectiveness and tolerability of atypical and typical antipsychotic medications (AP) in a non-interventional setting. This was a comparative, non-randomised, prospective, open-label, observational study. Treatment over the first 5 days was classified according to whether any olanzapine, risperidone, or haloperidol was included or not. Documentations (PANSS-excited component, CGI-aggression, CGI-suicidality, tranquilisation score) were at baseline (day 1) and days 2-6 after start of AP. During the short treatment-period, PANSS-EC and CGI-aggression scores improved in all cohorts. 68.7% of patients treated with olanzapine, 72.2% of patients treated with risperidone, and 83.3% of patients treated with haloperidol received concomitant benzodiazepines (haloperidol vs. non-haloperidol: p < 0.001). More patients treated with olanzapine (73.8%) were fully alert according to a tranquilisation score and active at day 2 than patients treated with risperidone (57.1%) or haloperidol (58.0%). Current medication practices for immediate aggression control are effective with positive results present within a few days. In this study, concomitant benzodiazepine use was significantly more frequent in patients receiving haloperidol.
    Full-text · Article · Jul 2008 · BMC Psychiatry
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    • "Diagnoses were documented according to the International Classification of Diseases, 10th revision (WHO, 1992). At all visits, the following instruments were completed: The Excited Component (PANSS-EC; Kay and Sevy, 1990; Breier et al., 2002; Meehan et al., 2002) of the Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987), comprising the items " poor impulse control " , " tension " , " hostility " , " uncooperativeness " , and " excitement " and rated on a seven point Likert scale from " absent " to " extremely severe " (score range from 5 to 35 points). To ensure the validity of PANSS-EC ratings, definitions of each PANSS-EC item were provided on the same sheet where the respective ratings had to be documented. "
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    ABSTRACT: Clinical management of aggression depends on the availability of easily administrable measurements allowing reliable evaluation. The present study's aim is to validate a Clinical Global Impression-Severity of Aggression scale (CGI-A). 558 inpatients with psychiatric disorders and an agitated-aggressive syndrome at baseline were continuously assessed over 5 days using CGI-A and the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC). Equipercentile linking, correlation analyses and linear regression were applied. Relationship between CGI-A and PANSS-EC total score was found to be linear. On a 5-level CGI-A scale, values of 1 to 5 points were found to correspond to PANSS-EC scores of 12.2, 16.7, 21.3, 25.8, and 30.4, respectively (average increase: 4.6). All findings remained stable when only data from patients with schizophrenia spectrum disorders were analyzed. The CGI-A is proposed as a quickly administrable scale for the assessment of patients' aggressiveness.
    Full-text · Article · Apr 2008 · Schizophrenia Research
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