Acute Bipolar Mania
Conditions
Keywords
Acute bipolar mania, Seroquel XR, Seroquel XR plus lithium, Quetiapine fumarate
Brief summary
The primary objective of this study is to compare the efficacy of Seroquel XR monotherapy compared with Seroquel XR plus lithium in the treatment of acute bipolar mania by evaluation of the changes from baseline in Young Mania Ratings Scale (YMRS) total score to Day 29 using the last observation carried forward method.
Detailed description
A comparison of the effectiveness of Seroquel XR and Seroquel XR plus lithium in patients with acute bipolar mania: An open-label, randomized, parallel groups, rater-blinded, 4 week, multicenter, comparative, phase 4 study.
Interventions
DRUGQuetiapine fumarate
eXtended Release(XR) 50mg, 200mg, 300mg and/or 400mg tablet, oral, once daily in the evening, from assignment to the end of the study.
DRUGlithium
300mg tablet, oral
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Female and/or male inpatients or outpatients, aged over 18 years and under 65 years * Documented clinical diagnosis meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria * YMRS total score =20 at enrollment and randomization (Day 1) Patients had a history of at least one manic episode that required hospitalization and/or treatment with a mood stabilizer or antipsychotic. * Female patients must have a negative urine human chorionic gonadotropin (HCG) test at enrolment and must be using a reliable method of birth control, ie, barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive
Exclusion criteria
* Pregnancy or lactation Meeting the criteria for any other (than bipolar disorder) DSM-IV Axis I diagnosis, concomitant organic mental disorder or mental retardation * Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others * Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomization/baseline * Known intolerance or hypersensitivity to, or lack of response to previous treatment with quetiapine fumarate or lithium
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Changes From Baseline in Young Mania Rating Scale (YMRS) Total Score to Day 29 | From Baseline to Day 29 | The Young Mania Rating Scale (YMRS) is an eleven-item, multiple-choice diagnostic questionnaire which psychiatrists use to measure the severity of manic episodes. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. Total score is summed of 11items. Total score rage is from 0 to 60 and the higher score represent a worse oucome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline up to Day 29 and Final Assessment in the Clinical Global Impression-Severity of Illness Scale (CGI-S) | From Baseline to Day 29 | The Severity of Illness scale (CGI-S) is scored to rate the patient's current clinical state. The score range is form 0 to 7. A CGI-S score of 1 indicates that a patient is Normal, not at all ill and a score of 7 indicates that a patient is Among the most extremely ill patients. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Seroquel XR Seroquel XR: 300mg, After that, 400mg to 800mg, Study medication will be administered orally, once daily in the evening.
Treatment duration: 28 days | 63 |
| Seroquel XR + Lithium Seroquel XR: 300mg, After that, 400mg to 800mg Study medication will be administered orally, once daily in the evening Lithium will be started with 300mg tid on Day 1 then adjusted between the 900mg/day and 1200mg/day from Day 2 within lithium concentration \[0.8\
1.2mEq/L\].
Treatment duration: 28 days | 58 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 4 | 2 |
| Overall Study | Lost to Follow-up | 0 | 4 |
| Overall Study | technical problum | 1 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 11 |
| Overall Study | Wrongly randomization | 0 | 1 |
Baseline characteristics
| Characteristic | Seroquel XR | Seroquel XR + Lithium | Total |
|---|---|---|---|
| Age, Continuous Age | 38.4 Years STANDARD_DEVIATION 9.8 | 36.9 Years STANDARD_DEVIATION 11.7 | 37.7 Years STANDARD_DEVIATION 10.7 |
| Age, Customized Age at onset of acute bipolar mania | 31.0 Years STANDARD_DEVIATION 10.6 | 30.0 Years STANDARD_DEVIATION 11.3 | 30.5 Years STANDARD_DEVIATION 10.9 |
| Bipolar I Disorder Manic Episodes | 57 Number of Patients in ITT analysis set | 51 Number of Patients in ITT analysis set | 108 Number of Patients in ITT analysis set |
| Bipolar I Disorder Mixed Episodes | 6 Number of Patients in ITT analysis set | 7 Number of Patients in ITT analysis set | 13 Number of Patients in ITT analysis set |
| Sex: Female, Male Female | 37 Participants | 34 Participants | 71 Participants |
| Sex: Female, Male Male | 26 Participants | 24 Participants | 50 Participants |
| Total No. of acute bipolar mania episodes over lifetime | 4.24 Episodes STANDARD_DEVIATION 4.31 | 3.25 Episodes STANDARD_DEVIATION 2.42 | 3.76 Episodes STANDARD_DEVIATION 3.54 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 52 / 68 | 49 / 62 |
| serious Total, serious adverse events | 2 / 68 | 2 / 62 |
Outcome results
Primary
The Changes From Baseline in Young Mania Rating Scale (YMRS) Total Score to Day 29
The Young Mania Rating Scale (YMRS) is an eleven-item, multiple-choice diagnostic questionnaire which psychiatrists use to measure the severity of manic episodes. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. Total score is summed of 11items. Total score rage is from 0 to 60 and the higher score represent a worse oucome.
Time frame: From Baseline to Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seroquel XR | The Changes From Baseline in Young Mania Rating Scale (YMRS) Total Score to Day 29 | -13.7 scores on the scale | Standard Deviation 13.8 |
| Seroquel XR + Lithium | The Changes From Baseline in Young Mania Rating Scale (YMRS) Total Score to Day 29 | -15.5 scores on the scale | Standard Deviation 13.3 |
Secondary
The Change From Baseline up to Day 29 and Final Assessment in the Clinical Global Impression-Severity of Illness Scale (CGI-S)
The Severity of Illness scale (CGI-S) is scored to rate the patient's current clinical state. The score range is form 0 to 7. A CGI-S score of 1 indicates that a patient is Normal, not at all ill and a score of 7 indicates that a patient is Among the most extremely ill patients.
Time frame: From Baseline to Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seroquel XR | The Change From Baseline up to Day 29 and Final Assessment in the Clinical Global Impression-Severity of Illness Scale (CGI-S) | -1.37 scores on the scale | Standard Deviation 1.52 |
| Seroquel XR + Lithium | The Change From Baseline up to Day 29 and Final Assessment in the Clinical Global Impression-Severity of Illness Scale (CGI-S) | -1.58 scores on the scale | Standard Deviation 1.56 |