Agitation-Calmness Evaluation Scale Research Articles

Inhaled Loxapine as a Rapid Treatment for Agitation in Patients with Personality Disorder: A Prospective Study on the Effects of Time.

ObjectiveAgitation in patients diagnosed with personality disorders (PD) is one of the most frequent crises in emergency departments (ED). Although many medications have been tested, their effectiveness has been small or non-significant, and no specific drugs are supported by the available evidence. This study aimed to evaluate the efficacy of Inhaled loxapine (IL) as a therapeutic option for agitated patients with PD.MethodsA naturalistic, unicentric, prospective study was carried out. Thirty subjects diagnosed with PD and attending the ED with episodes of agitation were recruited most of whom were women diagnosed with Borderline Personality Disorder. Subjects were treated with a single dose of IL (9.1 mg). Efficacy was assessed with the Clinical Global Impression scale, the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) and the Agitation-Calmness Evaluation Scale (ACES). Patients were followed 60 minutes after administration to measure IL effect and its duration.ResultsIL exhibited an overall efficacy in managing mild to severe agitation, with a quick onset of effect and persistence. ‘Effect of time’, where IL efficacy is maintained over time, is more marked in higher-severity agitation. No additional treatments were needed to improve agitation during the follow-up time.ConclusionResults suggest that IL could be a safe and effective option to manage agitation in PD.

Comparison of sublingual and intravenous administration of lorazepam in psychiatric emergencies in emergency medical services

Agitation is afrequent reason for emergency physician calls in psychiatric emergencies in the German preclinical emergency medical system. Benzodiazepines have proven to be effective in treating acute agitation. Although lorazepam has beneficial clinical and pharmacological properties it is hardly used by emergency physicians. The sublingual administration of lorazepam has many advantages compared to intravenous administration. In an interventional trial lasting 18months the efficacy, tolerance and onset of effects of sublingual and intravenous lorazepam in patients with agitation states in emergency duties were compared. The randomization to the intervention groups was subject to atime criterion. The sublingual administration of lorazepam over a period of 9months was followed by an intravenous administration over the same period of time. The psychometric scales used were: PANSS-EC, CGI, CGI-Change, agitation-calmness evaluation scale, visual analog scale and sedation scale. Response to the intervention was defined by a40% reduction on the PANSS-EC scale. A total of 37individuals participated in the study (sublingual: n = 22, intravenous: n = 15). Lorazepam was effective in treating acute agitation. The effectiveness and tolerance of sublingual and intravenous lorazepam administration seems to be comparable. Sublingual administration of lorazepam is effective for treating acute agitation in emergency medical services.

Intramuscular olanzapine for agitated patients: A systematic review and meta-analysis of randomized controlled trials

We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) of intramuscular (IM)-olanzapine (OLA-IM) versus controls in agitated patients. The risk ratio, number-needed-to-treat/harm, and standardized mean difference based on a random effects model were calculated. We identified 13 RCTs (19 comparisons) as follows: 7 comparisons with 1059 patients for OLA-IM versus placebo; 5 comparisons with 613 patients for OLA-IM versus haloperidol (HAL)-IM; 2 comparisons with 108 patients for OLA-IM versus ziprasidone (ZIP)-IM; 2 comparisons with 110 patients for OLA-IM versus HAL-IM plus midazolam; and 3 comparisons with 412 patients for OLA-IM versus HAL-IM plus promethazine, 2 comparisons with 355 patients for OLA-IM versus lorazepam-IM (LOR-IM); and 1 comparison with 67 patients for OLA-IM versus HAL-IM plus LOR-IM. OLA-IM was superior to placebo in both Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and Agitation–Calmness Evaluation Scale (ACES) scores 2 h after first injection, and had a comparable side effect profile, including over sedation, extrapyramidal symptoms, akathisia, and anticholinergic use. While there was no significant difference in PANSS-EC scores after 2 h between OLA-IM and HAL-IM, OLA-IM outperformed HAL-IM in ACES after 2 h. Compared with HAL-IM, OLA-IM was associated with fewer side effects, including anticholinergic use, akathisia, extrapyramidal symptoms, and dystonia, and marginally less QT prolongation compared with HAL-IM. Based on our findings, OLA-IM is preferable to HAL-IM for the treatment of agitated patients. However, comparator data for ZIP-IM, LOR-IM and HAL-IM combination therapy were insufficient.

A naturalistic comparison study of the efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular levomepromazine in acute agitated patients with schizophrenia

This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine, IM haloperidol, and IM levomepromazine in acute agitated patients with schizophrenia. The subjects were 122 inpatients. Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS, and Agitation-Calmness Evaluation Scale, and their safety were assessed using the Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale (BARS), and Drug-induced Extrapyramidal Symptoms Scale (DIEPSS). The mean changes from baseline on the PANSS-EC, Agitation-Calmness Evaluation Scale, Abnormal Involuntary Movement Scale, BARS, and DIEPSS scores were significantly better in both IM olanzapine and IM levomepromazine than in IM haloperidol. Of these, the mean changes from baseline on the BARS and DIEPSS scores were significantly better in IM olanzapine than in IM levomepromazine. The mean change from baseline on the PANSS positive score was significantly better in both IM olanzapine and IM haloperidol than in IM levomepromazine. The results of this study suggest the possibility that the anti-agitation effects of IM olanzapine and IM levomepromazine are more rapid than those of IM haloperidol. No worsening of EPS was observed. Our results also suggest that compared with IM levomepromazine, IM olanzapine is safer and affords greater improvement in symptoms.

A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular haloperidol in agitated elderly patients with schizophrenia

This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine and IM haloperidol in agitated elderly patients with schizophrenia at 2 hours postdose. The subjects were 23 inpatients who had been diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS and Agitation Calmness Evaluation Scale (ACES), and their safety were assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and laboratory tests. The mean reduction from baseline on the PANSS-EC total score, the PANSS total score and the ACES score were significantly greater in the IM olanzapine injection group than in the IM haloperidol injection group. The mean changes from baseline on the AIMS score, the BARS score and the DIEPSS total score were significantly better in the IM olanzapine injection group than in the IM haloperidol injection group. No serious adverse events such as paralytic ileus, diabetic ketoacidosis, neuroleptic malignant syndrome or tardive dyskinesia occurred between the two groups. The results of this study suggest the possibility that agitated elderly patients may result in superior efficacy and safety after IM olanzapine without serious adverse events in comparison with IM haloperidol.

Intramuscular Aripiprazole in the Acute Management of Psychomotor Agitation

To assess acute efficacy and safety of 9.75 mg of intramuscular (IM) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation. Open-label trial of IM injections of aripiprazole and 24-hour monitoring of clinical response in patients with major psychoses and acute agitation. Partial analysis of blood levels of the administered drug to correlate with clinical response. Acute psychiatric care wards in a single university hospital. A total of 201 acutely agitated patients (79 with schizophrenia and 122 with bipolar disorder I). Aripiprazole 9.75 mg IM injection. We evaluated clinical response using the Excitatory Component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation/Calmness Evaluation Scale (ACES), and the Clinical Global Impressions scale (CGI). Assessments were conducted 30, 60, 90, and 120 minutes and 24 hours after the first injection for PANSS-EC and ACES, and 2, 4, 6, and 24 hours for CGI. Response was at least a 40% decrease in PANSS-EC scores. We measured serum aripiprazole and dehydroaripiprazole levels in a subsample. IM aripiprazole significantly improved clinical measures. PANSS-EC improved progressively, starting after 30 minutes. ACES improved after 90 minutes and continued thereafter. Effects were sustained, with steadily decreasing CGI scores, until the 24th hour. Response rate was 83.6% after 2 hours, but with repeat injections, it rose to over 90% with no differences among diagnostic groups. Although there were gender differences in the response to individual PANSS-EC items, the responses were similar overall. Neither clinical monitoring nor patient reporting revealed any side effects. No therapeutic window was identified, and levels did not correlate with any clinical measure. Aripiprazole was effective and safe in reducing acute agitation in patients with bipolar disorder or schizophrenia. Our results compare favorably to double-blind trials, probably due to higher expectations in trials involving no placebo arm. Absence of side effects could be related to the short observation time.

A prospective comparative study on naloxone combined haloperidol treatment for excited type delirium in elderly

Objective Compared with haloperidol treatment, naloxone and naloxone combined haloperidol treatments were assessed in their efficacy and safety for excited type delirium in elderly. Methods The elderly patients with delirium were divided into haloperidol treatment (H), naloxone treatment (N) and combined treatment (C) in a prospective randomized controlled design. Delirium score scale (DSS) was used before and after treatments respectively. Clinical global impression scale-severity of illness (CGI-SI) score was evaluated daily to assess the onset time and improvement of delirium. Agitation-calmness evaluation scale (ACES) observed calmness effect in agitated patients before and after every medication intervention. Treatment emergent symptom scale (TESS) assessed side effects of all medications. Results The duration of three groups(H(4.0±2.9)d, N(4.2±3.5)d, C(3.2±3.2)d) had no significant difference (P>0.05) by multiple comparison. Compared the onset time of three groups (H(2.4±1.6)d, N(2.4 ±1.4)d, C(1.3±0.9) d), the combined group was faster than the other two groups ( all P 0.05). DSS scores had no significant differences (P>0.05) in three groups before treatment, so did CGI-SI scores. In the end, DSS scores were(H: 18.8±11.5, N: 27.7±7.2, C: 29.5±5.6)respectively. Statistically naloxone group and combined group with no significant difference (P>0.05), were better than the haloperidol group (all P 0.05). Three groups had no significant difference in ACES scores (P>0.05) before and after medication interventions(H: 5.9±1.6, N: 6.2±1.8, C: 6.4±1.6)(P>0.05). Haloperidol group had 4 cases of extrapyramidal symptom evaluated by TESS and combined group had 2 cases. Two groups had no significant difference (Chi-square test P>0.05) in extrapyramidal symptom incidence. The naloxone group showed no side effects. Conclusion Naloxone combined haloperidol is slight better than naloxone, more than haloperidol in terms of efficacy. Haloperidol equally with combined medication showed more side effects than naloxone. Key words: Naloxone; Haloperidol; Treatment; Delirium; Elderly patients

A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular levomepromazine in agitated elderly patients with schizophrenia.

BackgroundThere have not been any reports in Japan clarifying the efficacy and safety of intramuscular (IM) olanzapine and IM levomepromazine in agitated elderly patients with schizophrenia. This study was a comparative investigation of the clinical efficacy and safety of IM olanzapine and IM levomepromazine in agitated elderly patients with schizophrenia at 2 hours post-dose.MethodsThe subjects were 52 inpatients who were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV. Their clinical symptoms were assessed using the Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS, and Agitation Calmness Evaluation Scale (ACES), and their safety was assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), and glucose test.ResultsThe PANSS-EC total score, the ACES score, and the glucose level significantly decreased from baseline in both the IM olanzapine group and the levomepromazine injection group; however, no between-group differences were observed. Mean change from baseline in the PANSS total score, positive score, the BARS score, and the DIEPSS total score was significantly greater in the IM olanzapine injection group compared with the levomepromazine injection group.ConclusionThe results of this study suggest that agitated elderly patients rapidly respond to IM olanzapine and IM levomepromazine treatment. Furthermore, these results suggest that IM olanzapine is safer than IM levomepromazine and causes greater improvement in positive symptoms.

Comparison of Intramuscular Olanzapine, Orally Disintegrating Olanzapine Tablets, Oral Risperidone Solution, and Intramuscular Haloperidol in the Management of Acute Agitation in an Acute Care Psychiatric Ward in Taiwan

The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

The Effects of Molindone as a Concomitant Medication on Aggressive Behavior

Background: After noting a significant reduction in aggression and agitation in treatment-refractory patients with molindone augmentation in severely aggressive inpatients, the authors conducted a retrospective medical records review to assess the possible anti-aggressive role of molindone treatment in a larger cohort of treatment-refractory inpatients. Method: Twenty-four weeks of data from thirty inpatients who were consecutively augmented with molindone, including progress notes, orders for seclusion, chemical restraint, and scores on the Agitation-Calmness Evaluation Scale (ACES) were systematically collected. The number of seclusions, number of as-needed medications (PRNs) and ACES scores were used to tabulate the frequency of aggression and agitation episodes during the 8-week period before, 8 weeks after, and 9 through 16 weeks after the initiation of molindone augmentation treatment. Results: Over the observation period of twenty-four weeks, the number of episodes of PRN medication administration ...

A Randomized, Double-Blind, Placebo-Controlled Tolerability Study of Intramuscular Aripiprazole in Acutely Agitated Patients With Alzheimer's, Vascular, or Mixed Dementia

To evaluate the tolerability of intramuscular (IM) aripiprazole in patients with agitation associated with dementia. A 24-hour, double-blind, placebo-controlled, randomized study. Sixteen healthcare facilities in the United States. A total of 129 patients with acute agitation associated with Alzheimer's, vascular or mixed dementia in healthcare facilities. Patients were randomized to IM aripiprazole (5 mg, 10 mg, or 15 mg) or IM placebo administered in divided doses 2 hours apart. Safety assessments included adverse event (AE) reporting, vital signs, and electrocardiograms. Preliminary efficacy analyses used the Positive and Negative Syndrome Scale-Excited Component (PEC) scores and Agitation-Calmness Evaluation Scale (ACES). There was greater incidence of AEs with IM aripiprazole (50% to 60%) than IM placebo (32.0%), but over 90% were mild or moderate in severity. The incidence of oversedation was low. PEC scores showed greater improvements in agitation with IM aripiprazole 10 mg and 15 mg compared with IM placebo. A total of 10 mg or 15 mg of IM aripiprazole administered in divided doses was safe and well tolerated for treatment of agitation associated with Alzheimer's, vascular, or mixed dementia in long-term care. Preliminary analysis showed greater efficacy compared with IM placebo.

Clinical characteristics of agitated psychotic patients treated with an oral antipsychotics attended in the emergency room setting: NATURA study

Purpose. Prospective observational study to describe the clinical characteristics of patients with acute psychosis and agitation who receive oral psychopharmacological treatment at psychiatric emergency services (PES). Methods. A total of 278 patients with acute psychosis and agitation were admitted to PES and received oral psychopharmacological treatment. Diagnosis at admission, agitation level at entry and discharge, use of mechanical restraints, pharmacological and time to reintervention were prospectively explored. Severity of the disease was evaluated according to the Positive and Negative Syndrome Scale–Excitement Component (PANSS-EC), Agitation Calmness Evaluation Scale (ACES) and Clinical Global Impression-Severity (CGI-S) at admission, before first reintervention (if any) and at discharge from PES. Results. Most prevalent diagnoses were schizophrenia (77%) and bipolar disorder (12.2%). Mean (SD) scores in rating scales at baseline and at discharge were, respectively: PANSS-EC, 20.38(5.3) and 13.04 (5.5); CGI-S, 3.86(1.1) and 2.17(0.9); and ACES, 2.35(0.6) and 3.60(1.1). A total of 21.6% (60/278) of the patients required mechanical restraints and 38.1% (106/278) reintervention. From the emergency room, 20.5% patients went home while 71.2% were transferred to inpatient units. Conclusion. Clinical characteristics of psychotic agitated patients may help in deciding which type of treatment should be used and may be useful for the design of future prospective trials to explore treatment of agitation.

Intramuscular Aripiprazole in the Control of Agitation

To evaluate response to intramuscular (IM) aripiprazole injections using secondary analyses from clinical trials. Data from one trial in patients with bipolar I disorder and two trials in patients with schizophrenia were assembled and used for three secondary analyses. Analysis 1 looked at data from "nonsedated" patients (i.e., patients with scores < 8 [deep sleep] or 9 [unarousable] on the Agitation-Calmness Evaluation Scale [ACES]). In analysis 2, patients were subdivided into "higher" and "lower" agitation groups according to a median split on the baseline score for the Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) (median = 18). Analysis 3 looked at the patients who received a second injection within the 24-hour study period. In each analysis, the mean change from baseline in PEC scores was re-evaluated. Analysis 1 found that nonsedated patients with bipolar I disorder and schizophrenia showed significant decreases in PEC scores following treatment with aripiprazole IM (p < 0.005). Analysis 2 found that aripiprazole IM significantly reduced agitation compared with placebo in patients with bipolar I disorder who had lower baseline agitation (p < 0.01), while patients with bipolar I disorder who had higher baseline agitation showed similarly large PEC decreases with aripiprazole (-9.9) and placebo (-7.9). Patients with schizophrenia showed significant reductions in PEC scores compared with placebo regardless of baseline level of agitation (p < 0.01). Analysis 3 found that a second injection of aripiprazole IM significantly reduced agitation in patients with bipolar I disorder or schizophrenia (p < 0.05); repeated injections were safe and well tolerated. Improvements with aripiprazole IM appeared to be specific to core agitation symptoms, as opposed to nonspecific sedation, and to be independent of baseline level of agitation. Furthermore, patients benefited from a repeated aripiprazole injection when clinically warranted. These results address important clinical issues regarding use of aripiprazole IM in treating agitation.

Management of Acute Agitation in Patients With Bipolar Disorder

To investigate the efficacy and safety of intramuscular (IM) aripiprazole for the treatment of agitation in patients with bipolar I disorder, manic or mixed episodes. In total, 301 patients experiencing acute agitation were randomized to IM aripiprazole 9.75 mg per injection (n = 78), IM aripiprazole 15 mg per injection (n = 78), IM lorazepam 2 mg per injection (n = 70), or IM placebo (n = 75) in this double-blind multicenter study. Patients could receive up to 3 injections over 24 hours. Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component score from baseline at 2 hours after first injection. Mean improvements in Positive and Negative Syndrome Scale Excited Component score at 2 hours were significantly greater with IM aripiprazole (9.75 mg, -8.7; 15 mg, -8.7) and IM lorazepam (-9.6) versus IM placebo (-5.8; P <or= 0.001). For all other efficacy measures, all 3 active treatments showed significantly greater improvements over IM placebo at 2 hours (P < 0.05), with similar improvements across the active treatments. Significant differences over IM placebo were seen by 45 to 60 minutes for several efficacy parameters. Both IM aripiprazole doses were well tolerated; the safety profile was similar to oral aripiprazole. Oversedation (Agitation-Calmness Evaluation Scale score of 8 or 9) during 2 hours after first injection was less frequent with IM aripiprazole 9.75 mg (6.7%) and IM placebo (6.8%) versus IM aripiprazole 15 mg (17.3%) and IM lorazepam (19.1%). IM aripiprazole 9.75 and 15 mg are effective and well tolerated for acute agitation in bipolar disorder, although the low incidence of oversedation suggests a risk-benefit profile for IM aripiprazole 9.75 mg.

Efficacy and Safety of Intramuscular Aripiprazole in Patients With Acute Agitation

This multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of intramuscular (IM) aripiprazole in patients with acute agitation with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or schizo-phreniform disorder. Patients were randomly assigned to IM aripiprazole 1 mg, 5.25 mg, 9.75 mg, or 15 mg; IM haloperidol 7.5 mg; or placebo and observed for 24 hours. The primary efficacy measure was mean change in the Positive and Negative Syndrome Scale-Excited Component (PEC) score from baseline to 2 hours after initial dosing. Secondary measures included the Agitation-Calmness Evaluation Scale (ACES) score. The study was carried out at 50 centers worldwide between April 2002 and January 2003. A total of 357 patients were randomly assigned to treatment. Intramuscular aripiprazole 5.25 mg, 9.75 mg, and 15 mg and IM haloperidol 7.5 mg demonstrated significantly greater reduction in the primary efficacy measure versus placebo. These changes were statistically significant as early as 45 minutes for the IM aripiprazole 9.75-mg group, with a trend toward significance (p = .051) at 30 minutes. Intramuscular haloperidol 7.5 mg first showed a significant reduction in PEC score versus placebo at 105 minutes. At 30 minutes, significantly more patients responded (defined as a greater than or equal to 40% reduction in PEC score) to IM aripiprazole 9.75 mg versus placebo (27% vs. 13%, p = .05). Intramuscular aripiprazole 9.75 mg significantly improved agitation, without oversedation, as measured by change in ACES score from baseline to 2 hours versus placebo (p = .003). No patient discontinued the study because of treatment-emergent adverse events. Extrapyramidal symptoms occurred most frequently in the IM haloperidol group. The most common adverse event in IM aripiprazole recipients was headache. Intramuscular aripiprazole 9.75 mg is a rapidly effective and well-tolerated alternative to IM haloperidol for the control of agitation, without oversedation, in patients with schizophrenia, schizo-affective disorder, or schizophreniform disorder. ClinicalTrials.gov identifier NCT00036127.

Efficacy of Topiramate, Valproate, and Their Combination on Aggression/Agitation Behavior in Patients With Psychosis

Topiramate is an antiepileptic drug, recently also used in the treatment of psychiatric diseases. Inasmuch as topiramate and valproate, which are currently used for aggressive behavior, share several pharmacological mechanisms (positive modulatory effect on the GABA activity and negative modulatory effect on glutamatergic neurotransmission), the objective of the present study was to compare the pharmacological effects of topiramate with those of valproate and their combination in patients with psychiatric disorders showing marked aggression and agitation. A retrospective, case-controlled, mirror-image study was carried out in a sample of 45 inpatients affected by schizophrenia, schizoaffective and bipolar disorder, and hospitalized in a maximum-security Canadian psychiatry hospital. Overt Aggression Scale, Agitation-Calmness Evaluation Scale, number and intensity of psychotic episodes, number of episodes of withdrawal from group activities per week, and number of therapeutic isolation per week and of strict surveillance intervention per week were evaluated before and after the treatments. Results indicate that patients treated with topiramate show a decrease in the average score of the Overt Aggression Scale, a decrease of episodes of agitation and of strict surveillance interventions. This effect was similar to the group treated with valproate or with the combination of valproate-topiramate. However, valproate therapy, but not topiramate therapy, decreased the intensity of agitation episodes measured by the Agitation-Calmness Evaluation Scale; valproate and the combination topiramate-valproate decreased the number of psychotic disorganization episodes as well. These results suggest that topiramate could be a valid medicine in the control of aggression in psychosis. Double-blind, randomized, placebo-controlled studies need to further assess this pharmacological indication.

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Calming versus sedative effects of intramuscular olanzapine in agitated patients

Distinct calming rather than nonspecific sedation is desirable for the treatment of acute agitation. In 3 double-blind studies, acutely agitated patients with schizophrenia (N = 311), bipolar mania (N = 201), or dementia (N = 206) were treated with intramuscular (1–3 injections/24 hrs) olanzapine (2.5–10.0 mg), haloperidol (7.5 mg), lorazepam (2.0 mg), or placebo. The Agitation-Calmness Evaluation Scale (ACES; Eli Lilly and Co.) and treatment-emergent adverse events assessed sedation. Across all studies, 1 patient (lorazepam-treated, bipolar) became unarousable. There were no significant between-group differences in ACES scores of deep sleep or unarousable at any time across. Excluding asleep patients, agitation remained significantly more reduced with olanzapine than placebo ( P < .05). The incidences of adverse events indicative of sedation were not significantly different with olanzapine versus comparators. For the treatment of acute agitation associated with schizophrenia, bipolar mania, or dementia, intramuscular olanzapine-treated patients experienced no more sedation than haloperidol- or lorazepam-treated patients and experienced distinct calming rather than nonspecific sedation.

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

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 ⩾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.