Culturally Adapted Psychoeducation for Bipolar Disorder in a Low-resource Setting: A Randomized Controlled Trial

Study Overview
=================
Brief Summary
-----------------
Study objectives: To determine the effectiveness of the CaPE intervention compared to treatment as usual (TAU) in reducing the time to recurrence for people with bipolar disorder (BD) I/II, currently in remission in Pakistan To determine the impact of the CaPE intervention compared to TAU on clinical outcomes, quality of life and functioning; and To estimate the cost-effectiveness of CaPE in a low-resource setting (i.e., Pakistan) (if the RCT confirms the effectiveness of CaPE in BD. Study design and setting: This will be a multi-centre, assessor blind, individual, parallel-arm randomized controlled trial (RCT) with Pakistani patients with BD. Sample Size: The study aims to recruit a total of N=300 participants in total.

Detailed Description
-----------------
Psychoeducation (PE) is an effective adjunctive treatment option in BD, however, despite the clear benefits, there are only limited, underpowered studies of PE from LMICs, including Pakistan. Therefore, the current study aims to test the effectiveness of Culturally adapted PsychoEducation (CaPE) intervention for people with BD in Pakistan. The study will include a total of N=300 people with BD from psychiatric units of teaching and non-teaching hospitals in 8 centres across Pakistan including Karachi, Lahore, Multan, Rawalpindi, Peshawar, Hyderabad, Shaheed Benazirabad and Quetta. Consented participants meeting eligibility criteria will be randomised in a 1:1 allocation to CaPE or TAU. Randomization will be computer generated and use a random permuted block method with variable block sizes stratified by site, bipolar type (I or II) and self-reported sex. Participants in CaPE intervention group will receive 12-weekly one-to-one psychoeducation sessions. Each CaPE session will last for approximately 1 hour, beginning with a 20-30-minute presentation on the topic of the day, followed by a related exercise (e.g., drawing a life chart or compiling a list of potential triggers for recurrence). Sessions will be delivered by trained psychologists who will receive regular weekly supervision to maintain fidelity. The other group will receive TAU/control group. Assessments will be carried out at baseline, months 3, 6, and 12 either in-person and/or via secure videoconference software (alternatives to in-person for COVID-19 or travel restrictions) by trained, blinded research analysts (RAs). The treatment groups will be compared with each other at baseline and then at subsequent follow-ups at 3, 6 and 12 months. We will also conduct in-depth, one-to-one interviews with service users from the intervention arm (15-20), carers (15-20) and all therapists involved in the trial. A cost-utility analysis from a healthcare system and societal perspective will be conducted to establish the cost-effectiveness of CaPE against TAU.

Official Title
-----------------
Culturally Adapted Psychoeducation for Bipolar Disorder in a Low-resource Setting: A Randomized Controlled Trial

Conditions
-----------------
Bipolar Disorder

Intervention / Treatment
-----------------
* Behavioral: Culturally adapted Psychoeducation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult outpatients age 18 and above Diagnosis of Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) bipolar disorder (both BD I and BD II), currently in remission, confirmed by Structured Clinical Interview for DSM-5 (SCID) Currently euthymic (Hamilton Depression Rating Scale, HDRS-17 < 8 and Young Mania Rating Scale, YMRS <8) Able to give written informed consent On stable psychiatric medication regimen for at least 3 months Resident of the trial catchment area. Exclusion Criteria: Active substance use disorder, based on DSM-5 criteria Currently experiencing recurrence (mania, hypomania, mixed or depressive Active suicidal ideation Unstable residential arrangements that reduce likelihood of being available for the duration of trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CaPE Intervention<br>CaPE is a manualized intervention consisting of 12 one-to-one psychoeducation sessions, one session per week. Each session will last for 60 minutes. All sessions will be delivered by a trained therapist who will receive two months training from senior therapists before starting intervention. | Behavioral: Culturally adapted Psychoeducation<br>* This is a culturally adapted psychoeducation program consisting of 12 sessions. Each CaPE session lasts for approximately 60 minutes, beginning with a 20-30-minute presentation on the topic of the day, followed by a related exercise (e.g., drawing a life chart or compiling a list of potential triggers for recurrence).<br>|
| No Intervention: Treatment as Usual<br>Treatment as usual (TAU) will be ascertained by the participant's treating physician. Research staff will record the nature and intensity of TAU delivered to each participant over a period of 3 months. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal Interval Follow-up Evaluation | Longitudinal Interval Follow-up Evaluation (LIFE) is an integrated system for assessing the longitudinal course of psychiatric disorders. The assessment will consist of a semi-structured interview, during which an interviewer uses the LIFE to collect detailed psychosocial, psychopathologic, and treatment information for the follow-up interval. The weekly psychopathology measures are ordinal symptom-based scales with categories defined to match the criteria of the DSM-5. | Change in scores from baseline to months 3, 6, and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographic Questionnaire | Demographic Questionnaire will be used to assess baseline demographics including age, gender, self-reported sex, marital status, smoking status, employment status, education and monthly income. | Baseline | 
| Young Mania Rating Scale | Young Mania Rating Scale (YMRS) will be used to assess manic symptom severity. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. | Change in scores from baseline to months 3, 6, and 12 | 
| Hamilton Depression Rating Scale | Hamilton Depression Rating Scale (HDRS-17) is a clinician-administered scale that will be used to measure severity of depression symptoms. | Change in scores from baseline to months 3, 6, and 12 | 
| Quality of life scale | EuroQol-5D (EQ- 5D) EQ-5D will be used to assess health-related quality of life over 5 dimensions (mobility, self-care, daily activities, pain-discomfort, anxiety and depression) 44. It also includes and a Visual Analogue Scale that evaluates patients' perceived health status. | Change in scores from baseline to months 3, 6, and 12 | 
| Bipolar Recovery Questionnaire | Bipolar Recovery Questionnaire (BRQ) is a 36-item questionnaire that will be used to measure functioning and personal experiences of recovery specific to patients with BD. | Change in scores from baseline to months 3, 6, and 12 | 
| Morisky Medication Adherence Scale-4 items | Morisky Medication Adherence Scale-4-item will be used to measure medication adherence. | Change in scores from baseline to months 3, 6, and 12 | 
| Bipolar Knowledge and Attitudes Questionnaire | Bipolar Knowledge and Attitudes Questionnaire (BKAQ) is a 25-item questionnaire developed for use in primary care to assess knowledge and attitudes towards bipolar disorder. | Change in scores from baseline to months 3, 6, and 12 | 
| Client Service Receipt Inventory | Client Service Receipt Inventory (CSRI) is a tool used to collect information on the whole range of services and supports study participants may be accessing. | From baseline to months 3, 6, and 12 |