Quetiapine Extended Release (XR) for the Management of Psychotic Aggression or Agitation in Adult Acute Psychiatry

Determining the Efficacy and Tolerance of Quetiapine Extended Release (XR) for the Management of Psychotic Aggression or Agitation in Adult Acute Psychiatry

This study is a multi-site study examining the use of Quetiapine XR for psychotic aggression in an acute psychiatric setting. The study aims to demonstrate that management with Quetiapine XR significantly reduces aggressive behaviour in acute patients with psychosis, significantly reduces psychotic symptoms and decreases the requirement for sedation using benzodiazepines.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia; Psychosis
• Intervention / Treatment: Drug: Quetiapine XR

Detailed Description

Aggression is a common occurrence in acute psychiatry as the experience of schizophrenia or related psychotic symptoms significantly increases the risk of aggressive behaviour. This can have detrimental effects on the provision of therapy and safety for staff and other patients.

Current practice in managing aggression in acute psychiatry often involves the addition of a sedating antipsychotic or benzodiazepine to a main atypical antipsychotic that is continued as a primary treatment.

Quetiapine IR (immediate release) has been found effective in the treatment and management of schizophrenia. Quetiapine acts in the brain on cell receptors to which serotonin (a chemical produced in the brain) binds. Serotonin is proposed to play a significant role in impulsive aggression. Additionally, sedation is a side effect of Quetiapine, which may also facilitate its use in aggression. However, Quetiapine is not commonly used in the management of aggression in acute psychiatry due to the amount of time required to achieve an optimal dose (up to 5 days).

Quetiapine XR (extended release) is an extended release formulation of Quetiapine that can be initiated at a higher dose, a therapeutic dose can be achieved more rapidly and is taken once per day instead of twice.

This study is a multi-site study examining the use of Quetiapine XR for psychotic aggression in an acute psychiatric setting. The study aims to demonstrate that management with Quetiapine XR significantly reduces aggressive behaviour in acute patients with psychosis, significantly reduces psychotic symptoms and decreases the requirement for sedation using benzodiazepines.

The participants will be in-patients experiencing psychotic aggression (determined by psychiatrist). For those patients experiencing aggression (which is not severe enough to require intramuscular injection), the treating clinician will make a decision whether or not to treat with Quetiapine XR. Those patients meeting inclusion/exclusion criteria will be observed over 8 days using measures that rate symptoms, aggression and possible side effects (these include observation, questionnaire and review of patient files).

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital, Melbourne
    • Melbourne, Victoria, Australia, 3004
      • Alfred Psychiatry Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or Females aged 18-65 years;
2. Determined by a psychiatrist to be experiencing acute psychotic symptoms (includes mania with psychotic features and drug-induced psychosis);
3. Determined by a psychiatrist to have acted aggressively (score of > 1 on the OAS);
4. Inpatient status at enrollment;
5. Patient agreement to take oral medication;
6. Provision of written informed consent when considered able to provide consent by the treating team;
7. Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrollment.

Exclusion Criteria:

1. Pregnancy or lactation;
2. Any DSM-IV Axis I disorder not defined in the inclusion criteria;
3. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others;
4. Known intolerance or lack of response to quetiapine fumarate or any other atypical psychotics, as judged by the investigator;
5. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir;
6. Use of any of the following cytochrome P450 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids;
7. Administration of a depot antipsychotic injection within one dosing interval (for the depot) prior to being recruited for the trial;
8. Patients receiving treatment with an antipsychotic other than Seroquel XR (either IM or oral) within one dosing interval prior to being recruited for the trial;
9. Patients receiving treatment with mood stabiliser or anti-depressant medication within 7 days prior to treatment with Seroquel XR;
10. Substance or alcohol abuse or dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria;
11. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment;
12. Unstable or inadequately treated renal, hepatic, cardiovascular, respiratory, cerebrovascular, or other serious progressive physical disease as judged by the investigator;
13. Involvement in the planning and conduct of the study;
14. Previous enrolment in the present study;
15. Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements;

16. A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:

    • Unstable DM defined as enrolment glycosylated hemoglobin (HbA1c) >8.5%;
    • Admitted to hospital for treatment of DM or DM related illness in past 12 weeks;
    • Not under physician care for DM;
    • Physician responsible for patient's DM care has not indicated that patient's DM is controlled;
    • Physician responsible for patient's DM care has not approved patient's participation in the study;
    • Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomisation. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks;
    • Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks.
17. An absolute neutrophil count (ANC) of > 1.5 x 109 per liter;
18. Refusal to take oral medication and intramuscular antipsychotic medication is administered instead.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Quetiapine XR; The study population will be patients admitted to the acute psychiatry inpatient wards of St Vincent's or the Alfred and determined by a Psychiatrist to be experiencing a psychotic illness (including mania with psychotic features and drug-induced psychosis) and acting in an aggressive manner (determined by a score of at least 1 on the OAS).	Drug: Quetiapine XR; The daily dose of oral Quetiapine XR at the start of therapy is 300 mg on Day 1, 600 mg on Day 2 and up to 800 mg after Day 2. The dose will be adjusted within the usual effective dose range of 400 to 800 mg/day, depending on the clinical response and tolerability of the individual patient.; Other Names: Seroquel XR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary efficacy variable is the change in aggression between admission and day 8 of treatment with Quetiapine XR as measured by the OAS.	Daily from baseline to day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Measuring psychotic symptomatology change from baseline in BPRS-Total Score in aggressive, psychotic patients managed with Quetiapine XR	Baseline, day 4, day 8
Measuring the incidence of adverse events (including Extrapyramidal symptoms) by the change from baseline in SAS and BAS and subjective reports	Baseline, day 3, 4, 5, 7, 8
Measuring the incidence of concomitant benzodiazepine and other permitted medication use	Daily

Collaborators and Investigators

• Sponsor: Bayside Health
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Jayashri Kulkarni, Prof, Alfred Psychiatry Research Centre

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Anticipated): October 1, 2010
• Study Completion (Anticipated): October 1, 2010

Study Registration Dates

• First Submitted: September 11, 2009
• First Submitted That Met QC Criteria: September 28, 2009
• First Posted (Estimate): September 29, 2009

Study Record Updates

• Last Update Posted (Estimate): September 29, 2009
• Last Update Submitted That Met QC Criteria: September 28, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Psychosis; Aggression; Acute; Quetiapine XR
• Additional Relevant MeSH Terms: Behavioral Symptoms; Schizophrenia Spectrum and Other Psychotic Disorders; Aggression; Schizophrenia; Psychotic Disorders; Mental Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate
• Other Study ID Numbers: D1443C00043