Bipolar Disorder
Conditions
Keywords
Cost effectiveness, Bipolar disorder, Mixed episodes, Quality of life
Brief summary
To evaluate the effectiveness of three systematic interventions for Bipolar Disorder (BD) mixed episodes using medications available in the Brazilian Public Healthcare System (SUS), and assessment of the quality of life of these patients. A randomized pragmatic trial was conducted. An algorithm was developed for the treatment of episodes of bipolar mixed episodes.
Detailed description
The study design was that of a pragmatic randomized clinical trial to evaluate the effectiveness of treatments for mood disorders in a public healthcare context in the city of Porto Alegre, in southern Brazil. The algorithm was originally developed for the treatment of mixed episodes by a Delphi panel of experts from psychiatric associations in Brazil. All subjects provided an informed consent form, in writing, in order to participate in the study protocol, which was approved by the institutional ethics committee. Procedures and measurements of the study The subjects under evaluation were selected and they followed the stages defined by the treatment protocol: 1. Sample selection by being referred from the primary healthcare clinics in the municipality; 2. Informative talk about mood disorders and the research, with the informed consent forms being provided to the subjects; 3. Screening for BD mixed episodes with the use of the Patient Health Questionnaire (PHQ-9), and Hypomanic Symptoms Checklist Brazilian Version (HCL -32-BV); 4. Diagnostic evaluation through the Mini International Neuropsychiatric Interview (MINI) and clinical interview for individuals with positive results in the screening instruments; 5. Baseline and demographic assessments using standardized semi-structured interviews in the first and second visits; 6. In each clinic visit, the severity of the symptoms were evealuated using the Clinical Global Impression Scale (CGI), Hamilton Rating Scale for Depression (HRSD), and Young Manic Rating Scale (YMRS); 7. Biweekly follow-up, changed to monthly after stabilization - with a maximum follow-up period of 52 weeks.
Interventions
DRUGLithium
DRUGValproic Acid
DRUGCarbamazepine
Sponsors
Federal University of Rio Grande do Sul
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. ages between 18 and 65; 2. BD current acute mixed episode; 3. total capacity to understand and respond to self-applied instruments; 4. the presence of symptoms in the last 30 days; 5. abstinence for at least 30 days for drug addicts.
Exclusion criteria
1. presence of Organic Brain Syndrome (OBS); 2. pregnancy or lactation; 3. criteria for psychiatric hospitalization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response to Treatment | 8 weeks | Response to treatment was defined as a 50% reduction from baseline scores in Hamilton Rating Scale for Depression (HRSD)and Young Mania Rating Scale (YMRS) scales HRSD was developed to evaluate and quantify depression.Its abbreviated version,. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal. The cutoff points are: 8-17 for mild depression,18-24 for moderate depression, and 25 or more for severe depression. The maximum score being 52 on the 17-point scale. YMRS is is the most widely used assessment tool for manic symptoms. The scale consists of 11 items .The YMRS follows the style of the Hamilton Rating Scale for Depression (HAM-D) with each item given a severity rating. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/agressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Scores of YMRS \> 20 generates indicate mania |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Remission to Treatment | 8 months | The remission outcome was established as obtaining three consecutive visits with scores of values considered asymptomatic Hamilton Rating Scale for Depression(HRSD \<7 points) and Young Mania Rating Scale (YMRS \<6 points) during the trial. The subjects that were asymptomatic for at least 6-8 month were considered to be in partial remission and complete if at least 12 months without symptoms, according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). |
| Quality of Life - WHOQOL Bref Intrument | 12 weeks | Quality of Life - WHOQOL -BREF instrument scores scores 0-20 . higher scores mean a better outcome. The quality of life was assessed for entire algorithm. There were no comparisons between each arms of the study. |
Participant flow
Recruitment details
Response to treatment was assessed for the entire algorithm. There were no comparisons between the steps of each arm of the study
Participants by arm
| Arm | Count |
|---|---|
| Lithium Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (A) Started Lithium (900mg-1500mg)
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step.
2. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 3rd step.
3. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Lithium | 38 |
| Acid Valproic Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (B) Started Valproic Acid (1000mg-1500mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Valproic Acid | 35 |
| Carbamazepine Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (C) Started Carbamazepine (600mg-1200mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Carbamazepine | 34 |
| Total | 107 |
Baseline characteristics
| Characteristic | Acid Valproic | Carbamazepine | Lithium | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 34 Participants | 38 Participants | 107 Participants |
| Age, Continuous | 43.6 years STANDARD_DEVIATION 13.17 | 43.6 years STANDARD_DEVIATION 13.17 | 43.6 years STANDARD_DEVIATION 13.17 | 43.6 years STANDARD_DEVIATION 13.17 |
| Region of Enrollment Brazil | 35 participants | 34 participants | 38 participants | 107 participants |
| Sex: Female, Male Female | 28 Participants | 27 Participants | 31 Participants | 86 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 35 | 0 / 34 |
| other Total, other adverse events | 0 / 38 | 0 / 35 | 0 / 34 |
| serious Total, serious adverse events | 0 / 38 | 0 / 35 | 0 / 34 |
Outcome results
Primary
Number of Participants With Response to Treatment
Response to treatment was defined as a 50% reduction from baseline scores in Hamilton Rating Scale for Depression (HRSD)and Young Mania Rating Scale (YMRS) scales HRSD was developed to evaluate and quantify depression.Its abbreviated version,. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal. The cutoff points are: 8-17 for mild depression,18-24 for moderate depression, and 25 or more for severe depression. The maximum score being 52 on the 17-point scale. YMRS is is the most widely used assessment tool for manic symptoms. The scale consists of 11 items .The YMRS follows the style of the Hamilton Rating Scale for Depression (HAM-D) with each item given a severity rating. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/agressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Scores of YMRS \> 20 generates indicate mania
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lithium | Number of Participants With Response to Treatment | 31 Participants |
| Acid Valproic | Number of Participants With Response to Treatment | 28 Participants |
| Carbamazepine | Number of Participants With Response to Treatment | 27 Participants |
Secondary
Number of Participants With Remission to Treatment
The remission outcome was established as obtaining three consecutive visits with scores of values considered asymptomatic Hamilton Rating Scale for Depression(HRSD \<7 points) and Young Mania Rating Scale (YMRS \<6 points) during the trial. The subjects that were asymptomatic for at least 6-8 month were considered to be in partial remission and complete if at least 12 months without symptoms, according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
Time frame: 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lithium | Number of Participants With Remission to Treatment | 10 Participants |
| Acid Valproic | Number of Participants With Remission to Treatment | 9 Participants |
| Carbamazepine | Number of Participants With Remission to Treatment | 9 Participants |
Secondary
Quality of Life - WHOQOL Bref Intrument
Quality of Life - WHOQOL -BREF instrument scores scores 0-20 . higher scores mean a better outcome. The quality of life was assessed for entire algorithm. There were no comparisons between each arms of the study.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Quality of Life - WHOQOL Bref Intrument | 10.91 score on a scale | Standard Deviation 3.44 |
| Acid Valproic | Quality of Life - WHOQOL Bref Intrument | 10.91 score on a scale | Standard Deviation 3.44 |
| Carbamazepine | Quality of Life - WHOQOL Bref Intrument | 10.91 score on a scale | Standard Deviation 3.44 |