Comparison of Rapidly Acting Intramuscular Olanzapine, Lorazepam, and Placebo A Double-blind, Randomized Study in Acutely Agitated Patients with Dementia

Abstract

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),It has been estimated that 5% of people older than 65, and up to 20% of those aged 80 and older, are affected by dementia (Gurland and Cross 1982;Small and Jarvik 1982). Of these, nearly half exhibit behavioral disturbances, such as agitation, wandering, and violent outbursts (Kunik et al. 1994). Agitation has been defined as "inappropriate verbal, vocal, or motor activity not explainable by apparent needs or confusion" (CohenMansfield 1986), and includes both physically and verbally aggressive behaviors such as hitting, biting, and From the Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (KMM, HW, SRD, JRN, BJ, CMB, PDF, AB), Institute of Psychiatry, Medical University of South Carolina, Charleston, South Carolina (JEM), and Senior Choice Unit, Presbyterian Hospital, Oklahoma City, Oklahoma (LMB).Address correspondence to: Dr. Alan Breier, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, Tel.: (317) Fax: (317) 433-5101. Received February 12, 2001; revised May 23, 2001; accepted September 7, 2001.Online publication: 9/13/01 at www.acnp.org/citations/Npp 091301174.N EUROPSYCHOPHARMACOLOGY 2002 -VOL . 26 , NO . 4 Rapidly Acting IM Olanzapine in Dementia 495 screaming, and nonaggressive behaviors such as pacing, wandering, and continual requests for attention. In nursing home patients with dementia, the prevalence of these disturbances may be as high as 75% (Deutsch and Rovner 1991). Severe symptoms of agitation may require rapid treatment in the form of parenteral medication when a very rapid onset is required or when patients refuse or cannot take oral agents. In some instances, the use of medication is less desirable than alternative methods such as behavioral intervention. However, occasions arise where a pharmacological intervention is unavoidable and in the best interests of the patient. Lorazepam is commonly used for treatment of acute agitation, and the benzodiazepines are currently among the few agents available in a parenteral formulation for treatment of agitation. Use of orally administered atypical antipsychotics such as olanzapine and risperidone has met with some success in treating behavioral disturbances in patients with dementia (Clark et al. 2001;De Deyn et al. 1999;Katz et al. 1999;Street et al. 2000). A parenteral formulation of a second-generation antipsychotic might offer some advantage over their corresponding oral formulations due to faster onset of effect and utility where the patient cannot, or will not, accept oral treatment (Bianchetti et al. 1980;Schaffer et al. 1982). Rapid tranquilization with parenteral...

Psychosis and Antipsychotic Medications in Alzheimer’s Disease: Clinical Management and Research Perspectives

“…A parenteral formulation of olanzapine is in development and was shown in a preliminary study to be effective and safe for treatment of acute agitation in elderly patients with dementia [44]. While parenteral administration may be necessary for emergency treatment in patients with AD and a formulation that acts more rapidly would be a useful addition to available treatment options, parenteral administration is avoided in usual clinical circumstances.…”

Violence in older people with mental illness

“…Lorazepam has been studied in the acute management of agitation in dementia, an RCT demonstrating improvement in levels of agitation (Meehan 2002). Long-term treatment with benzodiazepines would not be advocated because of the increased risk of falls, the risk of paradoxical agitation and potential for dependence (Sink 2005).…”

Pharmacologic Management of Agitation in Alzheimer’s Disease

“…One conceptual path to approval is illustrated, however, by the recent FDA approval (http://www.fda.gov) of injectable ziprasidone with an indication 'for the treatment of acute agitation in schizophrenic patients for whom treatment with ziprasidone is appropriate and who need intramuscular antipsychotic medication for rapid control of the agitation', based on results from clinical trials in psychotic patients [15][16][17]. FDA approval may also be granted for the use of as yet unmarketed injectable olanzapine for the treatment of acute agitation in certain clinical populations including patients with dementia [18,19]. Future claims for treatment of persistent agitation might be made based upon antiagitation trials conducted across diagnostic groups.…”

“…Meehan et al [18] studied acute treatment of agitation with intramuscular olanzapine in 272 inpatients or nursing home residents with AD and/or vascular dementia. Patients were given up to three injections of olanzapine at 2.5 or 5.0 mg, lorazepam 1.0 or 0.5 mg, or placebo and were assessed within a 24-hour period.…”