Cost- Effectiveness and Quality of Life Assessment in Mood Disorder

Study Overview
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Brief Summary
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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
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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: Sample selection by being referred from the primary healthcare clinics in the municipality; Informative talk about mood disorders and the research, with the informed consent forms being provided to the subjects; Screening for BD mixed episodes with the use of the Patient Health Questionnaire (PHQ-9), and Hypomanic Symptoms Checklist Brazilian Version (HCL -32-BV); Diagnostic evaluation through the Mini International Neuropsychiatric Interview (MINI) and clinical interview for individuals with positive results in the screening instruments; Baseline and demographic assessments using standardized semi-structured interviews in the first and second visits; 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); Biweekly follow-up, changed to monthly after stabilization - with a maximum follow-up period of 52 weeks.

Official Title
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Assessment of Cost- Effectiveness Interventions and the Quality of Life in Patients With Mood Disorders Through Resources Available in Brazilian Public Health

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Lithium
* Drug: Valproic Acid
* Drug: Carbamazepine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ages between 18 and 65; BD current acute mixed episode; total capacity to understand and respond to self-applied instruments; the presence of symptoms in the last 30 days; abstinence for at least 30 days for drug addicts. Exclusion Criteria: presence of Organic Brain Syndrome (OBS); pregnancy or lactation; criteria for psychiatric hospitalization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lithium<br>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. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 3rd step. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step. Fourth step: Association with risperidone (1-6mg) | Drug: Lithium<br> <br> * Other names: carbolitium;|
| Active Comparator: Acid Valproic<br>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. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step. Fourth step: Association with risperidone (1-6mg) | Drug: Valproic Acid<br> <br> * Other names: depakene;|
| Active Comparator: Carbamazepine<br>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. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step. Fourth step: Association with risperidone (1-6mg) | Drug: Carbamazepine<br> <br> * Other names: tegretol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 8 months | 
| 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. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cost effectiveness, Bipolar disorder, Mixed episodes, Quality of life