Measurement-Based Care Vs. Standard Care for Major Depressive Disorder

Study Overview
=================
Brief Summary
-----------------
Major depressive disorder (MDD) is one of the leading causes of disability worldwide, indicated as one of the two most disabling mental disorders by the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 (Vos et al., 2020). Despite several effective pharmacological and psychosocial interventions available globally, only about one-third of depressed patients achieve remission (Xiao et al., 2021). There is a need to establish scalable clinical management practices which utilize biopsychosocial assessments, formulate a differential diagnosis, and provide evidence-based treatments for patients with MDD (Hong et al., 2021). While significant evidence for effectiveness of Measurement Based Care (MBC) is found in clinical settings from high and middle-income countries, assessments of MBC compared with usual care for the treatment of MDD are yet to be completed in low-resource settings like LMICs. The aim of this trial is to determine the efficacy and safety of MBC in patients with MDD in comparison with standard care in Pakistan. In order to reduce the variance found in treatment-as-usual and isolate the impact of MBC, standard care for this trial will limit medication choices to either paroxetine or mirtazapine.

Detailed Description
-----------------
Hypothesis: The rates of response and remission, and time to response and remission would be significantly shorter in the MBC group, without greater dropout rates and side effect burden, compared with the standard treatment group. Study design and setting This will be a multi-centre, with assessors blind to protocol and treatment group, parallel arm, randomized controlled trial (RCT). The study is a direct replication of a study conducted by Gou et al. (2015) in China. Participants Participants will be recruited from psychiatric units of teaching and non-teaching hospitals in 6 centres: Karachi (population 23 million), Lahore (population 10 million), Rawalpindi (population 3 million), Hyderabad (population 2 million) and Quetta (population 1 million) and Multan (1.8 million). Sample size The sample size of 120 participants for this exploratory trial is based on the study conducted by Guo et al.

Official Title
-----------------
A Randomized Controlled Trial of Measurement-Based Care Vs. Standard Care for Major Depressive Disorder in Pakistan

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: Measurement Based Care (MBC)
* Drug: Control/Standard-care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult outpatients age 18-65 of age Diagnosis of nonpsychotic MDD established by treating psychiatrists and confirmed by a checklist based on DSM-5 criteria at study entry Currently depressed with a score >17 on the 17-item Hamilton Depression Rating (HDRS-17) Able to communicate effectively and give written informed consent Resident of the trial catchment area. Exclusion Criteria: 1. Lifetime history of drug or alcohol dependence; 2. Diagnosis of bipolar, psychotic, obsessive-compulsive, or eating disorders confirmed with DSM-5 criteria 3. History of a lack of response or intolerance to either of the two protocol antidepressants (paroxetine and mirtazapine) 4. Currently pregnancy or breastfeeding; 5. Suicide attempts in the current depressive episode; 6. Any major medical condition contraindicating the use of the protocol antidepressants. -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 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
Interventional Model Description: Participants will be randomized in a 1:1 allocation to measurement-based vs. standard-care.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Measurement Based Care MBC<br>patients in the MBC group will receive treatment according to a schedule that includes individualized starting dosages, dosage adjustment, and medication changes to minimize side effects, maximize safety, and optimize the therapeutic benefit for each patient. | Drug: Measurement Based Care (MBC)<br>* Patients in both groups will receive either open-label paroxetine (20-50mg/day) or open-label mirtazapine (15-45mg/day), within the therapeutic dosage range recommended by the US Food and Drug Authority (Paxil -Highlights of Prescribing Medication, 2022; Remeron -Highlights of Prescribing Medication, 2022). Paroxetine, a selective serotonin reuptake inhibitor, is chosen because it has been one of the most commonly prescribed antidepressants, and mirtazapine, an alpha-2 antagonist, is chosen because it has a different mechanism of action. The treating psychiatrists will decide which of the antidepressants and dosages to prescribe, as long as they were within the study's recommended dosage ranges. patients in the MBC group will receive treatment according to a schedule that includes individualized starting dosages, dosage adjustment, and medication changes to minimize side effects, maximize safety, and optimize the therapeutic benefit for each patient.<br>|
| Active Comparator: Control/Standard-care<br>Local medical, psychiatric and family medicine services provide routine care according to their clinical judgment and available resources. Standard-care will be ascertained by the participant's treating physician. Research staff will record the nature and intensity of standard-care delivered to each participant. In current practice, MDD patients are not routinely referred for any psychological therapies in Pakistan. Standard-care in Pakistan largely comprises of pharmacotherapy. | Drug: Control/Standard-care<br>* Local medical, psychiatric and family medicine services provide routine care according to their clinical judgment and available resources. Standard-care will be ascertained by the participant's treating physician. Research staff will record the nature and intensity of standard-care delivered to each participant. In current practice, MDD patients are not routinely referred for any psychological therapies in Pakistan. Standard-care in Pakistan largely comprises of pharmacotherapy.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating (HDRS-17) - Response | is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from zero to 61. Response will be defined as a decrease of 50% from the baseline HAM-D score. | Change in scores from baseline to 3-month follow up (end of intervention) | 
| Hamilton Depression Rating (HDRS-17) - Remission | is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from zero to 61. Remission as a HAM-D score<7 | Change in scores from baseline to 3-month follow up (end of intervention) and 6-month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency, Intensity, and Burden of Side Effects Rating scale | is a self-report instrument assessing three domains of medication side effects within the past week: frequency, intensity, and burden (the degree to which side effects over the past week interfered with day-to-day functions). Each domain is rated on a 7-point (0-6) scale (frequency, ranging from no side effects to present all of the time; intensity, ranging from no side effects to intolerable; and burden, ranging from no impairment to unable to function). A low score (0-2) indicates that current treatment may continue; an intermediate score (3 or 4) suggests that side effects require attention, a high score (5 or 6) means that the current treatment is unacceptable and a decrease in dosage or a medication switch is needed. Will be administered in the MBC group only | Change in scores at each week for up to 12 weeks. | 
| Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) | A 16-item scale to measure the severity of depressive symptoms within the past week. On the QIDS-SR, higher scores indicate more severe depressive symptoms. Will be administered in the MBC group only | Change in scores at each week for up to 12 weeks. | 
| Hamilton Depression Rating (HDRS-17) - Severity | is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from zero to 61. Higher scores indicate higher severity. | Change in scores from baseline to 3-month follow up (end of intervention)and 6-month follow up | 
| Additional Side-effect Checklist | This additional side-effect checklist include some common side effects of ant-depressant medications, | Change in score from baseline to 3-month follow up and 6-month follow up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Major Depressive Disorder, Measurement Based Care MBC, Pakistan