Bipolar Disorder
Conditions
Keywords
Bipolar Disorder, Depression, Bipolar, Mania
Brief summary
This study will evaluate the relative effectiveness of risperidone Consta injections occurring every 2 weeks in contrast to treatment as usual in preventing symptomatic relapse and rates of rehospitalization or admission into respite care for bipolar patients. Hypothesis: Risperdal Consta injections every 2 weeks will reduce the number of symptomatic relapses into mania, hypomania, mixed state, or depression, as shown by key indicators that include symptomatic relapse, rehospitalizations, emergency or urgent care visits, respite care, and intensive outpatient treatment as compared to treatment as usual.
Detailed description
Bipolar disorder arguably represents the most difficult to treat of all psychiatric disorders. In fact, long-term stabilization is more the exception than the rule, and the majority of patients experience frequent relapses of illness. Studies have shown that both bipolar I and II patients spend about half of their weeks in a significant symptomatic state. Relapses and persistent illness result in substantial morbidity, mortality, and disability. Symptomatic recurrences happen as a result of breakthrough symptoms during active treatment and intermittent non-adherence. Therefore, enhanced control of symptoms, coupled with ensured adherence, is very likely to improve the long-term outcome of this difficult-to-treat condition. Risperidone has been shown to be effective in controlling symptoms of acute mania or mixed state in two registration monotherapy and one combination treatment study with lithium or valproate, as well as several smaller trials. However, longer-term treatment studies are relatively lacking. As well, although Risperdal Consta(TM) has been shown to be of benefit in prevention of relapse in patients with schizophrenia, relatively little longer-term data in bipolar disorder is available. Nonetheless, both risperidone and Risperdal Consta (TM) are likely to be highly efficacious for the maintenance prevention of relapse in bipolar disorder. Moreover, Risperdal Consta(TM) helps to ensure longer-term treatment effectiveness, both by better adherence and improved control of symptoms. The present study is intended to determine whether Risperdal Consta(TM) injections, added to ongoing pharmacotherapy, will improve outcome relative to treatment as usual.
Interventions
DRUGRisperdal (risperidone) Consta
Risperdal Consta (TM) will be administered every 2 weeks by deep intramuscular (IM) gluteal injection, by a trained health care professional. Injections will alternate between the two buttocks. The initial dose will be 25 mg IM every 2 weeks. A minimum dose of 25 mg. every 2 weeks will be maintained. At the clinician's discretion, the dose may be advanced to 37.5 mg. or 50 mg. In addition, the dose will be raised to 37.5 mg. or 50 mg. if the following conditions remain: (1) Young Mania Rating Scale (YMRS) score \> 12; or (2) Evidence of impending relapse; and no dose limiting side effect. If the 25 mg. dose is not tolerated, the dose can be held temporarily; however, attempts will be made to achieve and maintain the dose at 25 mg. (or higher) until the end of the study period.
DRUGTreatment as usual
Treatment was provided in this arm based solely on the choice of the treatment provider and participant. Treatment providers were not part of the study staff and were completely free to make treatment choices except that they were not allowed to select a long-acting injectible.
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Be physically healthy * 18-60 years of age * Have a DSM-IV diagnosis of bipolar disorder in any phase, but without current psychotic features; with a history of symptomatic relapse on four or more occasions over the last year prior to the initiation of study for the treatment of bipolar disorder (type I or II, manic, hypomanic, mixed, or depressive type), with at least 1 in the previous 6 months. * Have a screening Hamilton Rating Scale for Depression-17 item (HAM-D17) score of \> 8 or a Young Mania Rating Scale (YMRS) \> 8.
Exclusion criteria
* Have any medical condition that would preclude treatment with Risperdal Consta(TM) * Have type 2 diabetes * Have hyperlipidemia (baseline total cholesterol \>280) * Have any clinically significant unstable medical condition * Have currently active psychotic symptoms (hallucinations or delusions) or carry a diagnosis of another psychotic disorder (schizophrenia, schizoaffective disorder, delusional disorder) * Have a documentable history of non-response to Risperidal Consta (TM) * Have a score of 4 on the suicide item (item 3) of the HAM-D scale and/or a determination by the investigator of significant suicide risk * Require hospitalization between the screening and baseline visits, or require hospitalization immediately following baseline * Have a medical contraindication or hypersensitivity to risperidone or Risperdal Consta (TM)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Relapse-related Events Normalized to Unit Time | 12 months | The outcome was total number of events divided by number of months (normalized to unit time). This was be calculated by dividing the number of relapse related events by the number of months of participation. Relapse related events included: (1) YMRS score \> 14 or MADRS \> 15; (2) 20% or greater increase in the YMRS or MADRS scores from the previous study visit; (3) urgent care visit (psychiatric hospitalization; emergency department visit; referral for respite care, partial hospitalization, or intensive outpatient treatment) due to worsening mood symptoms; (4) a Clinical Global Impression Severity of Illness score \>3; (5) syndromal relapse (Diagnostic and Statistical Manual of Mental Disorders, 4th Editionfor manic, hypomanic, major depressive, or mixed episode met); (6) withdrawal from the study due to inefficacy; and (7) necessary clinical medication adjustments (NCAs). |
Countries
United States
Participant flow
Recruitment details
Referred by treating provider
Pre-assignment details
Diagnostic review prior to randomization
Participants by arm
| Arm | Count |
|---|---|
| Risperdal Consta Risperdal Consta injection in conjunction with existing treatment
Risperdal (risperidone) Consta: Risperdal Consta (TM) will be administered every 2 weeks by deep intramuscular gluteal injection, by a trained health care professional. Injections will alternate between the two buttocks. The initial dose will be 25 mg IM every 2 weeks. A minimum dose of 25 mg. every 2 weeks will be maintained. At the clinician's discretion, the dose may be advanced to 37.5 mg. or 50 mg. In addition, the dose will be raised to 37.5 mg. or 50 mg. if the following conditions remain: (1) YMRS score \> 12; or (2) Evidence of impending relapse; and no dose limiting side effect. If the 25 mg. dose is not tolerated, the dose can be held temporarily; however, attempts will be made to achieve and maintain the dose at 25 mg. (or higher) until the end of the study period. | 25 |
| Treatment As Usual Clinician and patient decide upon treatment, as in a non-research clinical setting. The only treatment exclusion is any form of risperidone. | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 6 |
| Overall Study | subject did not tolerate Consta | 1 | 0 |
| Overall Study | subject moved out of the area | 1 | 0 |
Baseline characteristics
| Characteristic | Treatment As Usual | Risperdal Consta | 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 | 25 Participants | 25 Participants | 50 Participants |
| Age, Continuous | 38.2 Years STANDARD_DEVIATION 10.2 | 42.8 Years STANDARD_DEVIATION 8.7 | 40.5 Years STANDARD_DEVIATION 9.45 |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 16 Participants | 14 Participants | 30 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 5 / 25 | 6 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Number of Relapse-related Events Normalized to Unit Time
The outcome was total number of events divided by number of months (normalized to unit time). This was be calculated by dividing the number of relapse related events by the number of months of participation. Relapse related events included: (1) YMRS score \> 14 or MADRS \> 15; (2) 20% or greater increase in the YMRS or MADRS scores from the previous study visit; (3) urgent care visit (psychiatric hospitalization; emergency department visit; referral for respite care, partial hospitalization, or intensive outpatient treatment) due to worsening mood symptoms; (4) a Clinical Global Impression Severity of Illness score \>3; (5) syndromal relapse (Diagnostic and Statistical Manual of Mental Disorders, 4th Editionfor manic, hypomanic, major depressive, or mixed episode met); (6) withdrawal from the study due to inefficacy; and (7) necessary clinical medication adjustments (NCAs).
Time frame: 12 months
Population: All randomized participants were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperdal Consta | Number of Relapse-related Events Normalized to Unit Time | 5.34 Events/month | Standard Deviation 2.35 |
| Treatment As Usual | Number of Relapse-related Events Normalized to Unit Time | 6.26 Events/month | Standard Deviation 3.24 |