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

Sponsor

Pakistan Institute of Living and Learning (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05431374

Collaborator

University of Toronto (Other)

120

Enrollment

Locations

Arms

14.9

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Measurement Based Care (MBC) Drug: Control/Standard-care	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized in a 1:1 allocation to measurement-based vs. standard-care.Participants will be randomized in a 1:1 allocation to measurement-based vs. standard-care.

Masking:

Single (Outcomes Assessor)

Masking Description:

This will be an assessor blind, randomized controlled trial. Due to the nature of the interventions, it will be impossible to blind clinicians in participating centres or the participants themselves. Before assessments, participants will be asked not to reveal any information about treatment to assessors. To avoid unblinding, outcome assessors will be located separately from treatment providers, and we will assign new outcome assessors in cases of unintentional unblinding

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 5, 2022

Anticipated Primary Completion Date :

May 30, 2023

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

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.	Drug: Measurement Based Care (MBC) 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.
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.	Drug: 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.

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.

Drug: Measurement Based Care (MBC)

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.

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.

Drug: Control/Standard-care

Outcome Measures

Primary Outcome Measures

Hamilton Depression Rating (HDRS-17) - Response [Change in scores from baseline to 3-month follow up (end of intervention)]
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.
Hamilton Depression Rating (HDRS-17) - Remission [Change in scores from baseline to 3-month follow up (end of intervention)]
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

Secondary Outcome Measures

Frequency, Intensity, and Burden of Side Effects Rating scale [Change in scores at each week for up to 12 weeks.]
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
Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) [Change in scores at each week for up to 12 weeks.]
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
Hamilton Depression Rating (HDRS-17) - Severity [Change in scores from baseline to 3-month follow up (end of intervention)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bolan Medical Complex	Quetta	Balochistan	Pakistan
2	Services Hospital	Lahore	Punjab	Pakistan
3	Nishtar Hospital	Multān	Punjab	Pakistan
4	Benazir Bhutto Hospital	Rawalpindi	Punjab	Pakistan	203393
5	Civil Hospital	Karachi	Sindh	Pakistan
6	Civil Hospital	Hyderabad		Pakistan