Clinical trial NCT02870283
Conditions: Bipolar Disorder
Keywords: Cost effectiveness Bipolar disorder Mixed episodes Quality of life
Sponsor: Federal University of Rio Grande do Sul
Start date: 2010-05-01; Completion date: 2015-09-01
Enrollment: 107 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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.

Arms: arm 1: 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) arm 2: 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) arm 3: 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)
Interventions: intervention 1: Lithium intervention 2: Valproic Acid intervention 3: Carbamazepine
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents: