Cost- Effectiveness and Quality of Life Assessment in Bipolar Disorder Depressive Episode

• Sponsor: Federal University of Rio Grande do Sul (Other)
• Overall Status: Completed
• CT.gov ID: NCT02918097
• Collaborator: (none)
• Enrollment: 78
• Arm: 1
• Duration (Months): 64

Study Details

Study Description

Brief Summary

To evaluate the effectiveness of an algorithm for Bipolar Disorder depressive episodes (BDD) using medications available in the Brazilian Public Healthcare System (SUS). Quality of life assessment of these patients was also employed.

A randomized pragmatic trial was conducted. An algorithm was developed for the treatment of episodes of bipolar disorder depression episodes.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Lithium Carbonate; Drug: Sertraline; Drug: Nortriptyline; Drug: Risperidone	Phase 4

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 bipolar disorder depressive 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 unipolar depression 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: This is a pragmatical clinical trial. The patients follow a pre-established algorithm About the participant flow the results the table to indicate the number of participants who received treatment in the whole algoritm, not in each step.This is a pragmatical clinical trial. The patients follow a pre-established algorithm About the participant flow the results the table to indicate the number of participants who received treatment in the whole algoritm, not in each step.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cost- Effectiveness and Quality of Life Assessment in Bipolar Disorder Depressive Episode
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lithium Carbonate Group Started: Lithium Carbonate (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 (LSL 0.6-0.8). Non responsive patients: 2nd step. Second step: Monotherapy with lithium (LSL 1.0-1.2). Non responsive patients: 3rd step. Third step: Lithium + Sertraline (50mg-200mg). Non responsive patients: 4th step. Fourth step: Lithium + Nortriptyline 100mg. Non responsive patients: 5th step. Fifth step: Lithium + Nortriptyline 100mg + Sertraline (100mg-200mg). Non responsive patients: 6th step Sixth step: Lithium + Nortriptyline 100mg + Sertraline 200mg + Risperidone (1mg-6mg).

Drug: Lithium Carbonate; Other Names: Carbolitium ; Drug: Sertraline; Other Names: Zoloft ; Drug: Nortriptyline; Other Names: Pamelor ; Drug: Risperidone; Other Names: Risperdal

Outcome Measures

Primary Outcome Measures

1. 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

2. Quality of Life Instrument Scores [12 weeks]

   Quality of Life - WHOQOL -BREF instrument scores scores 0-20 . higher scores mean a better outcome.

Secondary Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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. -

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Federal University of Rio Grande do Sul

Investigators

• Principal Investigator: Marcelo Fleck, PhD, Federal University of Rio Grande do Sul

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ana Flávia Barros da Silva Lima, Principal Investigator, Federal University of Rio Grande do Sul
• ClinicalTrials.gov Identifier: NCT02918097
• Other Study ID Numbers: 09-013/2
• First Posted: Sep 28, 2016
• Last Update Posted: Nov 20, 2020
• Last Verified: Sep 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ana Flávia Barros da Silva Lima, Principal Investigator, Federal University of Rio Grande do Sul: Cost effectiveness; Bipolar disorder; Depressive episodes; Quality of Life
• Additional relevant MeSH terms: Disease; Bipolar Disorder; Risperidone; Lithium Carbonate; Sertraline; Nortriptyline

Study Results

Participant Flow

Arm/Group Title	Lithium Carbonate
Arm/Group Description	Group Started: Lithium Carbonate (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 (LSL 0.6-0.8). Non responsive patients: 2nd step. Second step: Monotherapy with lithium (LSL 1.0-1.2). Non responsive patients: 3rd step. Third step: Lithium + Sertraline (50mg-200mg). Non responsive patients: 4th step. Fourth step: Lithium + Nortriptyline 100mg. Non responsive patients: 5th step. Fifth step: Lithium + Nortriptyline 100mg + Sertraline (100mg-200mg). Non responsive patients: 6th step Sixth step: Lithium + Nortriptyline 100mg + Sertraline 200mg + Risperidone (1mg-6mg). Lithium Carbonate Sertraline Nortriptyline Risperidone
Period Title: Overall Study
STARTED	78
COMPLETED	58
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Lithium Carbonate
Arm/Group Description	Group Started: Lithium Carbonate (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 (LSL 0.6-0.8). Non responsive patients: 2nd step. Second step: Monotherapy with lithium (LSL 1.0-1.2). Non responsive patients: 3rd step. Third step: Lithium + Sertraline (50mg-200mg). Non responsive patients: 4th step. Fourth step: Lithium + Nortriptyline 100mg. Non responsive patients: 5th step. Fifth step: Lithium + Nortriptyline 100mg + Sertraline (100mg-200mg). Non responsive patients: 6th step Sixth step: Lithium + Nortriptyline 100mg + Sertraline 200mg + Risperidone (1mg-6mg). Lithium Carbonate Sertraline Nortriptyline Risperidone
Overall Participants	78
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	40.4 (11.4)
Sex: Female, Male (Count of Participants)
Female	61 78.2%
Male	17 21.8%
Region of Enrollment (participants) [Number]
Brazil	78 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Response to Treatment"
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lithium Carbonate
Arm/Group Description	Group Started: Lithium Carbonate (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 (LSL 0.6-0.8). Non responsive patients: 2nd step. Second step: Monotherapy with lithium (LSL 1.0-1.2). Non responsive patients: 3rd step. Third step: Lithium + Sertraline (50mg-200mg). Non responsive patients: 4th step. Fourth step: Lithium + Nortriptyline 100mg. Non responsive patients: 5th step. Fifth step: Lithium + Nortriptyline 100mg + Sertraline (100mg-200mg). Non responsive patients: 6th step Sixth step: Lithium + Nortriptyline 100mg + Sertraline 200mg + Risperidone (1mg-6mg). Lithium Carbonate Sertraline Nortriptyline Risperidone
Measure Participants	78
Count of Participants [Participants]	65 83.3%

2. Primary Outcome

Title	Quality of Life Instrument Scores
Description	Quality of Life - WHOQOL -BREF instrument scores scores 0-20 . higher scores mean a better outcome.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lithium Carbonate
Arm/Group Description	Group Started: Lithium Carbonate (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 (LSL 0.6-0.8). Non responsive patients: 2nd step. Second step: Monotherapy with lithium (LSL 1.0-1.2). Non responsive patients: 3rd step. Third step: Lithium + Sertraline (50mg-200mg). Non responsive patients: 4th step. Fourth step: Lithium + Nortriptyline 100mg. Non responsive patients: 5th step. Fifth step: Lithium + Nortriptyline 100mg + Sertraline (100mg-200mg). Non responsive patients: 6th step Sixth step: Lithium + Nortriptyline 100mg + Sertraline 200mg + Risperidone (1mg-6mg). Lithium Carbonate Sertraline Nortriptyline Risperidone
Measure Participants	78
Mean (Standard Deviation) [score on a scale]	10.58 (3.64)

3. Secondary Outcome

Title	Number of Participants With Remission to Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lithium Carbonate
Arm/Group Description	Group Started: Lithium Carbonate (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 (LSL 0.6-0.8). Non responsive patients: 2nd step. Second step: Monotherapy with lithium (LSL 1.0-1.2). Non responsive patients: 3rd step. Third step: Lithium + Sertraline (50mg-200mg). Non responsive patients: 4th step. Fourth step: Lithium + Nortriptyline 100mg. Non responsive patients: 5th step. Fifth step: Lithium + Nortriptyline 100mg + Sertraline (100mg-200mg). Non responsive patients: 6th step Sixth step: Lithium + Nortriptyline 100mg + Sertraline 200mg + Risperidone (1mg-6mg). Lithium Carbonate Sertraline Nortriptyline Risperidone
Measure Participants	78
Count of Participants [Participants]	21 26.9%

Adverse Events

Time Frame	18 months
Arm/Group Title	Lithium Carbonate
Arm/Group Description	Group Started: Lithium Carbonate (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 (LSL 0.6-0.8). Non responsive patients: 2nd step. Second step: Monotherapy with lithium (LSL 1.0-1.2). Non responsive patients: 3rd step. Third step: Lithium + Sertraline (50mg-200mg). Non responsive patients: 4th step. Fourth step: Lithium + Nortriptyline 100mg. Non responsive patients: 5th step. Fifth step: Lithium + Nortriptyline 100mg + Sertraline (100mg-200mg). Non responsive patients: 6th step Sixth step: Lithium + Nortriptyline 100mg + Sertraline 200mg + Risperidone (1mg-6mg). Lithium Carbonate Sertraline Nortriptyline Risperidone
All Cause Mortality
	Lithium Carbonate
	Affected / at Risk (%)	# Events
Total	0/78 (0%)
Serious Adverse Events
	Lithium Carbonate
	Affected / at Risk (%)	# Events
Total	0/78 (0%)
Other (Not Including Serious) Adverse Events
	Lithium Carbonate
	Affected / at Risk (%)	# Events
Total	0/78 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.