Cost- Effectiveness and Quality of Life Assessment in Mood Disorder

• Sponsor: Federal University of Rio Grande do Sul (Other)
• Overall Status: Completed
• CT.gov ID: NCT02870283
• Collaborator: (none)
• Enrollment: 107
• Arms: 3
• Duration (Months): 64

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Lithium; Drug: Valproic Acid; Drug: Carbamazepine	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 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of Cost- Effectiveness Interventions and the Quality of Life in Patients With Mood Disorders Through Resources Available in Brazilian Public Health
• 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
Active Comparator: 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. 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; Other Names: carbolitium
Active Comparator: 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. 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; Other Names: depakene
Active Comparator: 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. 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; Other Names: tegretol

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

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).

2. 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.

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: NCT02870283
• Other Study ID Numbers: 09-013
• First Posted: Aug 17, 2016
• Last Update Posted: Nov 20, 2020
• Last Verified: Aug 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; Mixed episodes; Quality of life
• Additional relevant MeSH terms: Disease; Bipolar Disorder; Mood Disorders; Carbamazepine; Valproic Acid

Study Results

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

Arm/Group Title	Lithium	Acid Valproic	Carbamazepine
Arm/Group Description	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) Lithium	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) Valproic Acid	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) Carbamazepine
Period Title: Overall Study
STARTED	38	35	34
COMPLETED	35	26	15
NOT COMPLETED	3	9	19

Baseline Characteristics

Arm/Group Title	Lithium	Acid Valproic	Carbamazepine	Total
Arm/Group Description	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) Lithium	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) Valproic Acid	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) Carbamazepine	Total of all reporting groups
Overall Participants	38	35	34	107
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	38 100%	35 100%	34 100%	107 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.6 (13.17)	43.6 (13.17)	43.6 (13.17)	43.6 (13.17)
Sex: Female, Male (Count of Participants)
Female	31 81.6%	28 80%	27 79.4%	86 80.4%
Male	7 18.4%	7 20%	7 20.6%	21 19.6%
Region of Enrollment (participants) [Number]
Brazil	38 100%	35 100%	34 100%	107 100%

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	Acid Valproic	Carbamazepine
Arm/Group Description	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) Lithium	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) Valproic Acid	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) Carbamazepine
Measure Participants	38	35	34
Count of Participants [Participants]	31 81.6%	28 80%	27 79.4%

2. 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	Acid Valproic	Carbamazepine
Arm/Group Description	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) Lithium	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) Valproic Acid	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) Carbamazepine
Measure Participants	38	35	34
Count of Participants [Participants]	10 26.3%	9 25.7%	9 26.5%

3. Secondary Outcome

Title	Quality of Life - WHOQOL Bref Intrument
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lithium	Acid Valproic	Carbamazepine
Arm/Group Description	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) Lithium	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) Valproic Acid	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) Carbamazepine
Measure Participants	35	26	15
Mean (Standard Deviation) [score on a scale]	10.91 (3.44)	10.91 (3.44)	10.91 (3.44)

Adverse Events

Arm/Group Title	Lithium		Acid Valproic		Carbamazepine
Arm/Group Description	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) Lithium		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) Valproic Acid		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) Carbamazepine
All Cause Mortality
	Lithium		Acid Valproic		Carbamazepine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/35 (0%)		0/34 (0%)
Serious Adverse Events
	Lithium		Acid Valproic		Carbamazepine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/35 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Lithium		Acid Valproic		Carbamazepine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/35 (0%)		0/34 (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.