Acute Agitation in Emergency Psychiatry

Advancing the Quality of Treatment and Care for Acute Agitation in Emergency Psychiatry

The purpose of the study is to improve the pharmacological treatment of psychiatric patients with acute agitation.

Study Overview

• Status: Recruiting
• Conditions: Agitation
• Intervention / Treatment: Drug: Sublingual Dexmedetomidine; Drug: Buccal midazolam; Drug: Oral lorazepam

Detailed Description

The initial treatment of acute agitation aims to reduce suffering, abort the immediate risk of harm to self or others, and prevent the use of coercive measures such a physical and mechanical restraint. With this research project, we aim to build the initial structure of a visionary platform design and to examine the efficacy, tolerability, and safety of two hitherto under-investigated compounds versus the current standard of care for acutely agitated patients when de-escalation techniques have failed. After obtaining the results of the initial phase, we plan to apply for future funding to maintain and expand the platform design with the addition of relevant experimental arms. The proposed platform design aims to anwer the question What is the best treatment for acutely agitated patients in inpatient psychiatric settings?

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Lone Baandrup, MD, DMSc; Phone Number: 00 45 91165903; Email: lone.baandrup@regionh.dk
• Study Contact Backup: Name: Marie Vang Jensen, MD; Phone Number: 0045 6199 7358; Email: marie.said.vang.jensen@regionh.dk

Study Locations

• Denmark
  • Copenhagen N, Denmark, 2400
    • Recruiting
    • Mental Health Center Copenhagen, Bispebjerg
    • Contact: Lone Baandrup; Phone Number: 0045 91165903; Email: lone.baandrup@regionh.dk
    • Contact: Marie Vang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-64 years
• Agitation with the need for tranquillization in inpatient psychiatric settings including psychiatric emergency rooms
• Total score of ≥14 on the PANSS Excited Component (PEC)
• A score ≥4 on at least 1 of the 5 items of the PEC
• Informed consent obtained prior to the occurrence of the emergency

Exclusion Criteria:

• Involuntary psychiatric admission according to the Danish Mental Health Act
• Female patients who are breastfeeding
• Female patients aged <50 years and unable to perform a negative urine screen for pregnancy and not using safe contraceptives
• Body weight <50 kg
• Extreme obesity defined as estimated BMI≥ 40 kg/m2
• Clinical situations where acute administration of an antipsychotic is preferred to treat acute agitation (in the opinion of the investigator)
• The patient deemed unwilling or unable to cooperate with study procedures (in the opinion of the investigator)
• Insufficient language skills that interfere with reading, writing, and providing written informed consent in Danish or other available languages (in the opinion of the investigator)
• Clinical suspicion of contraindications for one of the treatment arms
• Use of benzodiazepines, other sedatives, or antipsychotic drugs in addition to usual treatment (i.e., additional PN sedative prescriptions) in the 4 hours before study treatment
• Known allergy to any of the study medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buccal midazolam	Drug: Buccal midazolam; Buccal midazolam 10 mg, possible second dose 10 mg after 2 hrs
Experimental: Sublingual dexmedetomidine	Drug: Sublingual Dexmedetomidine; Sublingual dexmedetomidine 180 mcg, possible second dose 90 mcg after 2 hrs
Active Comparator: Oral lorazepam	Drug: Oral lorazepam; Oral lorazepam 4 mg, possible second dose 4 mg after 2 hrs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Excited Component of the Positive and Negative Syndrome Scale (PEC)	The Excited Component of the Positive and Negative Syndrome Scale (PEC) consists of 5 clinician-rated items associated with agitation from the Positive and Negative Syndrome Scale (PANSS). Scores range from 5 to 35. Higher is worse.	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PEC score earliest time with difference	The earliest time where a statistically significant difference in agitation is apparent as measured by change from baseline PEC score (change from pre- to post-dose PEC score at 30, 60, 90, and 120 minutes)	30, 60, 90, and 120 minutes
Tranquillized or asleep	Proportion tranquillized or asleep (measured as ≤4 on the BARS**) by 30, 60, 90, and 120 minutes post-dose	30, 60, 90, and 120 minutes post-dose
Physical restraint	Proportion physically restrained from administration to 12 hours post-dose	12 hours post-dose
Mechanical restraint	Proportion mechanically restrained from administration to 12 hours post-dose	12 hours post-dose
Rescue medication	Proportion given rescue medication 4-12 hours post-dose	4-12 hours post-dose
Patient-reported satisfaction	Patient-reported satisfaction measured using 4 items from the Treatment Satisfaction Questionnaire for Medication II. Each item is answered on a 7-point Likert scale from 1 (extremely dissatisfied) to 7 (extremely satisfied). Score range is from 4 to 28. Higher is better.	From 2 to 24 hrs post-dose when the participant is able to cooperate

Collaborators and Investigators

• Sponsor: Lone Baandrup
• Collaborators: Capital Region's Pharmacy (Region Hovedstadens Apotek), Marielundvej 25, 2730 Herlev, Denmark; Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital
• Investigators: Principal Investigator: Lone Baandrup, MD, DMSc, Mental Health Center Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 22, 2024
• First Submitted That Met QC Criteria: December 22, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 30, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Emergency psychiatry
• Additional Relevant MeSH Terms: Aberrant Motor Behavior in Dementia; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Disease Attributes; Behavioral Symptoms; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Emergencies; Psychomotor Agitation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Anticonvulsants; Midazolam; Dexmedetomidine; Lorazepam
• Other Study ID Numbers: 2023-510201-18-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol will be available in the CTIS. After publication of primary and secondary outcomes, IPD will be handed over to the Danish National Archives where data will be archived for 25 years. IPD will be shared upon reasonable reuqest after publication of primary and secondary outcomes.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes