STUDY OBJECTIVE: We aim to determine the most efficacious of 3 common medication regimens for the sedation of acutely agitated emergency department (ED) patients.
METHODS: We undertook a randomized, controlled, double-blind, triple-dummy, clinical trial in 2 metropolitan EDs between October 2014 and August 2015. Patients aged 18 to 65 years and requiring intravenous medication sedation for acute agitation were enrolled and randomized to an intravenous bolus of midazolam 5 mg-droperidol 5 mg, droperidol 10 mg, or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg, or olanzapine 5 mg. The primary outcome was the proportion of patients adequately sedated at 10 minutes.
RESULTS: Three hundred forty-nine patients were randomized to the 3 groups. Baseline characteristics were similar across the groups. Ten minutes after the first dose, significantly more patients in the midazolam-droperidol group were adequately sedated compared with the droperidol and olanzapine groups: differences in proportions 25.0% (95% confidence interval [CI] 12.0% to 38.1%) and 25.4% (95% CI 12.7% to 38.3%), respectively. For times to sedation, the differences in medians between the midazolam-droperidol group and the droperidol and olanzapine groups were 6 (95% CI 3 to 8) and 6 (95% CI 3 to 7) minutes, respectively. Patients in the midazolam-droperidol group required fewer additional doses or alternative drugs to achieve adequate sedation. The 3 groups' adverse event rates and lengths of stay did not differ.
CONCLUSION: Midazolam-droperidol combination therapy is superior, in the doses studied, to either droperidol or olanzapine monotherapy for intravenous sedation of the acutely agitated ED patient.
BACKGROUND: Agitation and aggression are significant problems in acute psychiatric units. There is little consensus on which drug is most effective and safest for sedation of these patients.
AIMS: To compare the effectiveness and safety of haloperidol v. droperidol for patients with agitation and aggression.
METHOD: In a masked, randomised controlled trial (ACTRN12611000565943) intramuscular droperidol (10 mg) was compared with intramuscular haloperidol (10 mg) for adult patients with acute behavioural disturbance in a psychiatric intensive care unit. The primary outcome was time to sedation within 120 min. Secondary outcomes were use of additional sedation, adverse events and staff injuries.
RESULTS: From 584 patients, 110 were randomised to haloperidol and 118 to droperidol. Effective sedation occurred in 210 (92%) patients within 120 min. There was no significant difference in median time to sedation: 20 min (interquartile range 15-30, range 10-75) for haloperidol v. 25 min (IQR 15-30, range 10-115) for droperidol (P = 0.89). Additional sedation was used more often with haloperidol (13% v. 5%, P = 0.06), but adverse effects were less common with haloperidol (1% v. 5%, P = 0.12). There were 8 staff injuries.
CONCLUSIONS: Both haloperidol and droperidol were effective for sedation of patients with acute behavioural disturbance.
INTRODUCTION: Agitation is a major problem in acute schizophrenia. Only a few studies have tested antipsychotic agents in severely agitated patients, mainly because of legal issues. Furthermore, most studies were limited to the first 24 hours. We aimed to investigate the efficacy of oral haloperidol, risperidone, and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospective, randomized, rater-blinded, controlled design within a naturalistic treatment regimen.
METHODS: In total, 43 severely agitated patients at acute care psychiatric units were enrolled. Participants were randomly assigned to receive either daily haloperidol 15 mg, olanzapine 20 mg, or risperidone 2 to 6 mg over 5 days. Positive and Negative Syndrome Scale psychotic agitation subscale score was the primary outcome variable. A mixed-model analysis was applied.
RESULTS: All drugs were effective for rapid tranquilization within 2 hours. Over 5 days, the course differed between agents (P < 0.001), but none was superior. Dropouts occurred only in the risperidone and olanzapine groups. Men responded better to treatment than did women during the initial 2 hours (P = 0.046) as well as over the 5-day course (P < 0.001). No difference between drug groups was observed regarding diazepam or biperiden use.
CONCLUSIONS: Oral haloperidol, risperidone, and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders. Response to oral antipsychotics demonstrated a gender effect with poorer outcome in women throughout the study.
OBJECTIVE: To assess sublingual asenapine for acute agitation.
METHOD: Agitated adults 18-65 years (any diagnosis) presenting for treatment in an emergency department and found to have a score of ≥14 on the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) were randomized to receive either a single dose of a sublingual 10 mg tablet of asenapine or placebo. Primary outcome measure was change in the PANSS-EC score from baseline to 2 h after medication or placebo administration. Secondary outcomes included the percentage of responders with a ≥ 40% reduction from baseline on the PANSS-EC score at 2 h.
RESULTS: A total of 120 subjects were randomized, 60 each to sublingual asenapine or placebo. Mean (SE) baseline PANSS-EC scores for the asenapine-treated and placebo-treated subjects were 19.4 ± 0.66 and 20.1 ± 0.61, respectively. Mean PANSS-EC scores at endpoint (LOCF) was 7.4 ± 0.65 for the asenapine-treated subjects and 14.7 ± 0.98 for the placebo-treated subjects. Change in PANSS-EC score at 2 h was statistically significantly greater for the asenapine-treated subjects compared with the placebo-treated subjects. NNT for response vs. placebo was 3 (95% CI 2-4).
CONCLUSION: Sublingual asenapine was efficacious in the treatment of agitation with an effect size comparable to that observed in prior studies of intramuscular antipsychotics.
Studies of intramuscular (IM) olanzapine in Asian and Taiwanese populations are limited. This study examined the efficacy and safety of IM olanzapine in Taiwanese patients with schizophrenia and acute agitated behavior.This was a multicenter, double-blind, randomized, parallel study comparing the efficacy and safety of 10 mg/d IM olanzapine (n = 25) against 7.5 mg/d haloperidol (n = 24). The primary objective was to assess the change of agitation from baseline to 2 hours after the first IM injection on the Positive and Negative Symptom Scale-Excited Component Scale.The changes of Positive and Negative Symptom Scale-Excited Component Scale score from baseline to 2 hours after the first IM injection did not show statistically significant difference between study groups (olanzapine -9.0 ± 5.7, haloperidol -7.9 ± 4.0, P = 0.254). Both groups reported insomnia as the most common treatment-emergent adverse event, and no serious adverse event was reported.Intramuscular olanzapine and IM haloperidol are similarly effective antipsychotic agents in treating agitated symptoms in Taiwanese patients with schizophrenia. Both IM olanzapine and IM haloperidol were proven to be safe and well tolerated, which also provided alternative options in the treatment of patients with schizophrenia with agitation.
STUDY OBJECTIVE: Parenteral benzodiazepines or antipsychotics are often used to manage acute agitation in emergency department (ED) settings in which alternative strategies have failed or are not feasible. There are scant data comparing parenteral medication regimens. We aim to determine the efficacy and safety of intravenous droperidol or olanzapine as an adjunct to intravenous midazolam for rapid patient sedation.
METHODS: We undertook a randomized, double-blind, placebo-controlled, double-dummy, clinical trial in 3 EDs (August 2009 to March 2011). Adult patients (n=336) requiring intravenous drug sedation for acute agitation were randomized to receive a saline solution (control), droperidol (5 mg), or olanzapine (5 mg) bolus. This was immediately followed by incremental intravenous midazolam boluses (2.5 to 5 mg) until sedation was achieved. The primary outcome was time to sedation. Secondary outcomes were need for "rescue" drugs and adverse events.
RESULTS: Three hundred thirty-six patients were randomized to the 3 groups. Baseline characteristics were similar across groups. The differences in medians for times to sedation between the control and droperidol and control and olanzapine groups were 4 minutes (95% confidence interval [CI] 1 to 6 minutes) and 5 minutes (95% CI 1 to 6 minutes), respectively. At any point, patients in the droperidol and olanzapine groups were approximately 1.6 times more likely to be sedated compared with controls: droperidol and olanzapine group hazard ratios were 1.61 (95% CI 1.23 to 2.11) and 1.66 (95% CI 1.27 to 2.17), respectively. Patients in the droperidol and olanzapine groups required less rescue or alternative drug use after initial sedation. The 3 groups' adverse event profiles and lengths of stay did not differ.
CONCLUSION: Intravenous droperidol or olanzapine as an adjunct to midazolam is effective and decreases the time to adequate sedation compared with midazolam alone.
Intramuscular (IM) antipsychotics are preferred for efficient control of agitation symptoms. Previous studies have demonstrated that IM ziprasidone is efficacious and safe for treatment of agitation in schizophrenia. However, clinicians now recognize that racial differences may contribute to altered therapeutic response and tolerability. This study compared the efficacy and tolerability of IM ziprasidone versus IM haloperidol for the management of agitation in Chinese subjects with schizophrenia. Subjects with acute schizophrenia were randomized to either ziprasidone (n = 189, 10 to 20 mg as required up to a maximum of 40 mg/d) or haloperidol (n = 187, 5 mg every 4 to 8 hours to a maximum of 20 mg/d) for 3 days. Psychiatric assessments and adverse events were assessed at baseline, 2, 4, 24, 48, and 72 hours. In the ziprasidone group, 2.1% of subjects discontinued versus 3.7% in the haloperidol group. The least squares mean change (SE) from baseline to 72 hours in Brief Psychiatry Rating Scale total score was -17.32 (0.7) for ziprasidone (n = 167) and -18.44 (0.7) for haloperidol (n = 152), with a 95% confidence interval treatment difference of -0.7 to 2.9. Fewer subjects experienced adverse events after ziprasidone (n = 54, 28.6%) than haloperidol (n = 116, 62.0%), with a notably higher incidence of extrapyramidal symptoms in the haloperidol group (n = 69, 36.9%) compared to the ziprasidone group (n = 4, 2.1%). For controlling agitation in schizophrenia in this Chinese study, ziprasidone had a favorable tolerability profile and comparable efficacy and safety compared to haloperidol.
OBJECTIVE: The present study evaluated inhaled loxapine for the acute treatment of agitation in patients with bipolar I disorder.
METHODS: A Phase 3, randomized, double blind, placebo-controlled, parallel group inpatient study was performed at 17 psychiatric research facilities. Agitated patients (N=314) with bipolar I disorder (manic or mixed episodes) were randomized (1:1:1) to inhaled loxapine 5 mg or 10 mg, or inhaled placebo using the Staccato® system. Following baseline assessments, patients received Dose 1 and were evaluated for 24 hours. If required, up to two additional doses of study drug and/or lorazepam rescue medication were given. The primary efficacy endpoint was change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score two hours after Dose 1. The key secondary endpoint was the Clinical Global Impression-Improvement score at two hours after Dose 1. Additional endpoints included the changes from baseline in the PANSS-EC from 10 min through 24 hours after Dose 1. Safety was assessed by adverse events, vital signs, physical examinations, and laboratory tests.
RESULTS: For the primary and key secondary endpoints, both doses of inhaled loxapine significantly reduced agitation compared with placebo. Reduced agitation, as reflected in PANSS-EC score, was evident 10 min after Dose 1 with both doses. Inhaled loxapine was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications (dysgeusia was reported in 17% of patients receiving active drug versus 6% receiving placebo).
CONCLUSIONS: Inhaled loxapine provided a rapid, non-injection, well-tolerated acute treatment for agitation in patients with bipolar I disorder.
We aim to determine the most efficacious of 3 common medication regimens for the sedation of acutely agitated emergency department (ED) patients.
METHODS:
We undertook a randomized, controlled, double-blind, triple-dummy, clinical trial in 2 metropolitan EDs between October 2014 and August 2015. Patients aged 18 to 65 years and requiring intravenous medication sedation for acute agitation were enrolled and randomized to an intravenous bolus of midazolam 5 mg-droperidol 5 mg, droperidol 10 mg, or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg, or olanzapine 5 mg. The primary outcome was the proportion of patients adequately sedated at 10 minutes.
RESULTS:
Three hundred forty-nine patients were randomized to the 3 groups. Baseline characteristics were similar across the groups. Ten minutes after the first dose, significantly more patients in the midazolam-droperidol group were adequately sedated compared with the droperidol and olanzapine groups: differences in proportions 25.0% (95% confidence interval [CI] 12.0% to 38.1%) and 25.4% (95% CI 12.7% to 38.3%), respectively. For times to sedation, the differences in medians between the midazolam-droperidol group and the droperidol and olanzapine groups were 6 (95% CI 3 to 8) and 6 (95% CI 3 to 7) minutes, respectively. Patients in the midazolam-droperidol group required fewer additional doses or alternative drugs to achieve adequate sedation. The 3 groups' adverse event rates and lengths of stay did not differ.
CONCLUSION:
Midazolam-droperidol combination therapy is superior, in the doses studied, to either droperidol or olanzapine monotherapy for intravenous sedation of the acutely agitated ED patient.
Diseño del estudio»Ensayo controlado aleatorizado (ECA)
