Measurement-Based Care Vs. Standard Care for Major Depressive Disorder (MBC)

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Other: Measurement Based Care (MBC); Other: Control/Standard-care

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Hyderabad, Pakistan
    • Civil Hospital
  • Balochistan
    • Quetta, Balochistan, Pakistan
      • Bolan Medical Complex
  • Punjab
    • Lahore, Punjab, Pakistan
      • Services Hospital
    • Multān, Punjab, Pakistan
      • Nishtar Hospital
    • Rawalpindi, Punjab, Pakistan, 203393
      • Benazir Bhutto Hospital
  • Sindh
    • Karachi, Sindh, Pakistan
      • Civil Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult outpatients age 18-65 of age
2. Diagnosis of nonpsychotic MDD established by treating psychiatrists and confirmed by a checklist based on DSM-5 criteria at study entry
3. Currently depressed with a score >17 on the 17-item Hamilton Depression Rating (HDRS-17)
4. Able to communicate effectively and give written informed consent
5. 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.

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Measurement Based Care MBC; 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.	Other: Measurement Based Care (MBC); Patients in both groups will receive either open-label paroxetine (10-40mg/day) or open-label mirtazapine (7.5-45mg/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.
Active Comparator: Control/Standard-care; 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.	Other: Control/Standard-care; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating (HDRS-17) - Time to 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 HDRS-17 score.	Time from baseline to response (in weeks) (assessed upto 24 weeks).
Hamilton Depression Rating (HDRS-17) - Time to 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 HDRS-17 score<7	Time from baseline to remission (in weeks) (assessed upto 24 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 and 6-month follow up
Adverse Effect Checklist	This checklist includes some common adverse effects of antidepressant medications.	Rates of adverse effects from baseline to 6-month follow up
All-cause discontinuation	Discontinuation from participation in the study.	Time from baseline to all-cause discontinuation of antidepressant medication (assessed upto 24 weeks)

Collaborators and Investigators

• Sponsor: Pakistan Institute of Living and Learning
• Collaborators: University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Actual): May 30, 2023
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 23, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; Pakistan; Measurement Based Care MBC
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: MBC-Depression; Depression (Other Identifier: PILL)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Only anonymized data will be shared with researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No