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

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Risperidone; Drug: Sertraline; Drug: Nortriptyline; Drug: Lithium Carbonate

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 Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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
Quality of Life Instrument Scores	Quality of Life - WHOQOL -BREF instrument scores scores 0-20 . higher scores mean a better outcome.	12 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

Collaborators and Investigators

• Sponsor: Federal University of Rio Grande do Sul

Publications and helpful links

General Publications

• Lima AF, Miguel SR, Cohen M, Zimmermann JJ, Shansis FM, Cruz LN, Ziegelmann PK, Polanczyk CA, Fleck MP. Effectiveness evaluation of mood disorder treatment algorithms in Brazilian public healthcare patients. Braz J Psychiatry. 2018 Jan-Mar;40(1):26-34. doi: 10.1590/1516-4446-2016-2147. Epub 2017 Aug 21.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: September 25, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (ESTIMATE): September 28, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 20, 2020
• Last Update Submitted That Met QC Criteria: October 25, 2020
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Quality of Life; Bipolar disorder; Cost effectiveness; Depressive episodes
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Disease; Bipolar Disorder; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Antidepressive Agents, Tricyclic; Antimanic Agents; Adrenergic Uptake Inhibitors; Sertraline; Risperidone; Lithium Carbonate; Nortriptyline
• Other Study ID Numbers: 09-013/2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO