Bipolar Disorder
Conditions
Keywords
bipolar disorder, mania, depression
Brief summary
To assess the acute and long-term bimodal efficacy of QTP, as an adjunct to ongoing treatment with lithium (Li) or divalproex (DIV) or lamotrigine (LAM) or any combination of the three thereof, in a group of patients with an index episode of a mixed state in BD.
Interventions
DRUGquetiapine SR
quetiapine SR, dose range 200-600mg, each night QHS for 6mos
DRUGquetiapine sr placebo
quetiapine sr placebo, dose range 200-600mg, each night QHS for 6mos
Sponsors
AstraZeneca
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female; * Age 18 years and older * Patients on: * Li at a stable dose for 4 weeks or longer, and a serum level at screening of 0.5 mEq/l OR * DIV dose for 4 weeks or longer, and a serum level at screening of 45 g/ml OR * LAM (dosage/day ≥100mg) at a stable dose for 4 weeks or longer OR * Any combination 3a, 3b, or 3c * Patients meeting DSM-IV TR diagnosis of bipolar disorder, I or II, as assessed using the MINI, (Sheehan et al., 1998) PLUS any ONE of criteria 5 or 6 or 7 * Patients meeting DSM-IV TR diagnostic criteria for a mixed manic episode with Young Mania Rating Scale (YMRS) score\>/=14 and Montgomery Asberg Depression Rating Scale (MADRS) score\>/=14 * Patients meeting the criteria for a manic/hypomanic episode for at least 2 days with the simultaneous presence of Young Mania Rating Scale (YMRS) score\>/=14 PLUS Montgomery Asberg Depression Rating Scale (MADRS) score\>/=14 ; * Patients meeting DSM-IV TR diagnostic criteria for a major depressive episode with the simultaneous presence of MADRS score\>/=14 PLUS meeting the criteria for a manic/hypomanic episode for at least 2 days with the simultaneous presence of Young Mania Rating Scale (YMRS) score\>/=14
Exclusion criteria
* Patients with a current Axis I diagnosis of schizophrenia, schizophreniform disorder, schizotypal disorder, bipolar disorder with psychotic subtype, drug induced mania or AIDS induced mania * Women with a positive pregnancy test or who are lactating * Women of child-bearing potential who are not practicing a clinically accepted method of contraception * Patients with general medical conditions that contraindicate psychoactive medications or uncontrolled medical disorder or central nervous system diseases. * Patients whose clinical status requires inpatient or day hospital treatment * History of severe side effects associated with therapeutic doses of Li, DIV, LAM * Alcohol or drug dependent at time of enrollment * Suicidal at time of enrollment. * Current or previous exposure to QTP
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Whose Mood Improved According to MADRS and YMRS Scale Scores. | Baseline visit to week 24 | The primary outcome measure was assessed by 50% reduction in: 1. depression scores on the Montgomery Asberg Depression Rating Scale (MADRS), which ranges from 0 indicating no symptoms to 60 indicating most symptoms 2. mania scores on the Young Mania Rating Scale (YMRS), which ranges from 0 indicating no symptoms to 60 indicating most symptoms. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited in our University, Center for Healthcare Services, and by televison ads between Oct 2007 and January 2011.
Pre-assignment details
Patients screened over a 7 day period.
Participants by arm
| Arm | Count |
|---|---|
| Active Quetiapine SR mood stabilizer plus active quetiapine sr | 15 |
| Quetiapine SR Placebo mood stabilizer plus quetiapine SR placebo | 13 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | incarceration | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 4 |
| Overall Study | Lost to Follow-up | 7 | 4 |
Baseline characteristics
| Characteristic | Quetiapine SR Placebo | Active Quetiapine SR | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 15 Participants | 28 Participants |
| Age, Continuous | 32.1 years STANDARD_DEVIATION 9.8 | 35.5 years STANDARD_DEVIATION 10.1 | 34 years STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 13 participants | 15 participants | 28 participants |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 15 | 7 / 13 |
| serious Total, serious adverse events | 0 / 15 | 0 / 13 |
Outcome results
Primary
Number of Patients Whose Mood Improved According to MADRS and YMRS Scale Scores.
The primary outcome measure was assessed by 50% reduction in: 1. depression scores on the Montgomery Asberg Depression Rating Scale (MADRS), which ranges from 0 indicating no symptoms to 60 indicating most symptoms 2. mania scores on the Young Mania Rating Scale (YMRS), which ranges from 0 indicating no symptoms to 60 indicating most symptoms.
Time frame: Baseline visit to week 24
Population: Per Protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active Quetiapine S.R., 200-600mg, po, qd | Number of Patients Whose Mood Improved According to MADRS and YMRS Scale Scores. | MADRS | 4 participants |
| Active Quetiapine S.R., 200-600mg, po, qd | Number of Patients Whose Mood Improved According to MADRS and YMRS Scale Scores. | YMRS | 4 participants |
| Placebo Quetiapine S.R. 200-600mg, po, qd | Number of Patients Whose Mood Improved According to MADRS and YMRS Scale Scores. | MADRS | 4 participants |
| Placebo Quetiapine S.R. 200-600mg, po, qd | Number of Patients Whose Mood Improved According to MADRS and YMRS Scale Scores. | YMRS | 4 participants |