Trial Outcomes & Findings for Personalized Treatments for Depressive Symptoms in Patients With Advanced Heart Failure (NCT NCT03688100)

NCT ID: NCT03688100

Last Updated: 2024-03-19

Results Overview

PHQ-9 is used to measure depressive symptoms severity. The PHQ-9 is a self-report instrument that corresponds with the validated Primary Care Evaluation of Mental Disorders PRIME-MD clinician-administered instrument. The PHQ-9 measures all nine dimensions of depression assessed in the DSM criteria for MDD on a 0-3 scale. Minimum score = 0 (no depression). Maximum scores = 21 (worst depression)

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 494 participants
• Primary outcome timeframe: 6 months from baseline enrollment.
• Results posted on: 2024-03-19

Participant Flow

Participant milestones

Measure	Patients: Medication Management (MEDS) The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Patients: Behavioral Activation Therapy (BA) BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.	Caregivers: Medication Management (MEDS) Caregivers in the medication management group do not participate in the medication management intervention. Rather, the medication management intervention is delivered to patients and the effect of this intervention is on patient's caregivers' burden is measured by the Caregiver Burden Questionnaire.	Caregivers: Behavioral Activation Psychotherapy (BA) Caregivers in the behavioral activation group do not participate in the behavioral activation intervention. Rather, the behavioral activation intervention is delivered to patients and the effect of this intervention on patient's caregivers' burden is measured by the Caregiver Burden Questionnaire.
Overall Study STARTED	208	208	35	43
Overall Study COMPLETED	132	150	20	25
Overall Study NOT COMPLETED	76	58	15	18

Reasons for withdrawal

Measure	Patients: Medication Management (MEDS) The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Patients: Behavioral Activation Therapy (BA) BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.	Caregivers: Medication Management (MEDS) Caregivers in the medication management group do not participate in the medication management intervention. Rather, the medication management intervention is delivered to patients and the effect of this intervention is on patient's caregivers' burden is measured by the Caregiver Burden Questionnaire.	Caregivers: Behavioral Activation Psychotherapy (BA) Caregivers in the behavioral activation group do not participate in the behavioral activation intervention. Rather, the behavioral activation intervention is delivered to patients and the effect of this intervention on patient's caregivers' burden is measured by the Caregiver Burden Questionnaire.
Overall Study Lost to Follow-up	21	15	15	18
Overall Study Withdrawal by Subject	19	16	0	0
Overall Study Death	36	27	0	0

Baseline Characteristics

Personalized Treatments for Depressive Symptoms in Patients With Advanced Heart Failure

Baseline characteristics by cohort

Measure	Patients: Medication Management (MEDS) n=208 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Patients: Behavioral Activation Therapy (BA) n=208 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.	Caregivers: Medication Management (MEDS) n=35 Participants Caregivers of patients receiving the the above described Medication Management (MEDS) intervention were monitored for caregiver burden at 3, 6, and 12 months.	Caregivers: Behavioral Activation Therapy (BA) n=43 Participants Caregivers of patients receiving the the above described Behavioral Activation Psychotherapy (BA) intervention were monitored for caregiver burden at 3, 6, and 12 months.	Total n=494 Participants Total of all reporting groups
Age, Continuous MEAN AGE	61 years STANDARD_DEVIATION 16 • n=5 Participants	61 years STANDARD_DEVIATION 16 • n=7 Participants	55 years STANDARD_DEVIATION 16 • n=5 Participants	55 years STANDARD_DEVIATION 13 • n=4 Participants	61 years STANDARD_DEVIATION 16 • n=21 Participants
Age, Continuous MEDIAN AGE (IQR)	61 years n=5 Participants	64 years n=7 Participants	57 years n=5 Participants	59 years n=4 Participants	62 years n=21 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	88 Participants n=7 Participants	27 Participants n=5 Participants	30 Participants n=4 Participants	230 Participants n=21 Participants
Sex: Female, Male Male	123 Participants n=5 Participants	120 Participants n=7 Participants	8 Participants n=5 Participants	13 Participants n=4 Participants	264 Participants n=21 Participants
Race/Ethnicity, Customized Race · Caucasian/White	112 Participants n=5 Participants	121 Participants n=7 Participants	19 Participants n=5 Participants	28 Participants n=4 Participants	280 Participants n=21 Participants
Race/Ethnicity, Customized Race · Black/African-American	60 Participants n=5 Participants	62 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants	136 Participants n=21 Participants
Race/Ethnicity, Customized Race · Asian	14 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	25 Participants n=21 Participants
Race/Ethnicity, Customized Race · Other	22 Participants n=5 Participants	18 Participants n=7 Participants	8 Participants n=5 Participants	5 Participants n=4 Participants	53 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	171 Participants n=5 Participants	173 Participants n=7 Participants	24 Participants n=5 Participants	33 Participants n=4 Participants	401 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	32 Participants n=5 Participants	28 Participants n=7 Participants	7 Participants n=5 Participants	9 Participants n=4 Participants	76 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity · Missing	5 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	17 Participants n=21 Participants
Medications Angiotensin Receptor Blocker	66 Number of patients taking the medication n=5 Participants	69 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	135 Number of patients taking the medication n=21 Participants
Medications Loop Diuretic	142 Number of patients taking the medication n=5 Participants	137 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	279 Number of patients taking the medication n=21 Participants
Medications Opiate	65 Number of patients taking the medication n=5 Participants	51 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	116 Number of patients taking the medication n=21 Participants
Medications Angiotensin-Converting Enzyme Inhibitor	33 Number of patients taking the medication n=5 Participants	33 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	66 Number of patients taking the medication n=21 Participants
Medications Beta Blocker	135 Number of patients taking the medication n=5 Participants	133 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	268 Number of patients taking the medication n=21 Participants
Medications Aldosterone Antagonist	50 Number of patients taking the medication n=5 Participants	50 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	100 Number of patients taking the medication n=21 Participants
Medications Calcium Channel Blocker	48 Number of patients taking the medication n=5 Participants	49 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	97 Number of patients taking the medication n=21 Participants
Medications Digoxin	13 Number of patients taking the medication n=5 Participants	25 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	38 Number of patients taking the medication n=21 Participants
Medications Steroid	39 Number of patients taking the medication n=5 Participants	31 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	70 Number of patients taking the medication n=21 Participants
Medications Cannabinoid	7 Number of patients taking the medication n=5 Participants	5 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	12 Number of patients taking the medication n=21 Participants
Medications History of Antidepressant	60 Number of patients taking the medication n=5 Participants	26 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	86 Number of patients taking the medication n=21 Participants
Medications Anticoagulant	61 Number of patients taking the medication n=5 Participants	89 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	150 Number of patients taking the medication n=21 Participants
Medications Ivabradine	2 Number of patients taking the medication n=5 Participants	1 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	3 Number of patients taking the medication n=21 Participants
Medications Non-Loop Diuretic	3 Number of patients taking the medication n=5 Participants	2 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	5 Number of patients taking the medication n=21 Participants
Medications Statin	110 Number of patients taking the medication n=5 Participants	105 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	215 Number of patients taking the medication n=21 Participants
Medications Antiaggregant	31 Number of patients taking the medication n=5 Participants	40 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	71 Number of patients taking the medication n=21 Participants
Medications Antiarrhythmic	27 Number of patients taking the medication n=5 Participants	34 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	61 Number of patients taking the medication n=21 Participants
Medications Angiotensin Receptor Neprilysin Inhibitor	38 Number of patients taking the medication n=5 Participants	38 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	76 Number of patients taking the medication n=21 Participants
Medications Hydralazine and Nitrate	65 Number of patients taking the medication n=5 Participants	58 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	123 Number of patients taking the medication n=21 Participants
Medications Sodium-Glucose-Co-Transporter-2 Inhibitor	4 Number of patients taking the medication n=5 Participants	8 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	12 Number of patients taking the medication n=21 Participants
Medications ACE + ARB + Entresto	105 Number of patients taking the medication n=5 Participants	107 Number of patients taking the medication n=7 Participants	0 Number of patients taking the medication n=5 Participants	0 Number of patients taking the medication n=4 Participants	212 Number of patients taking the medication n=21 Participants
Location of Recruitment Inpatient	107 Participants n=5 Participants	99 Participants n=7 Participants	17 Participants n=5 Participants	22 Participants n=4 Participants	245 Participants n=21 Participants
Location of Recruitment Outpatient	101 Participants n=5 Participants	109 Participants n=7 Participants	18 Participants n=5 Participants	21 Participants n=4 Participants	249 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6 months from baseline enrollment.

Population: Intention-to-treat: We analyzed all participants in both arms who were randomized to their respective intervention

PHQ-9 is used to measure depressive symptoms severity. The PHQ-9 is a self-report instrument that corresponds with the validated Primary Care Evaluation of Mental Disorders PRIME-MD clinician-administered instrument. The PHQ-9 measures all nine dimensions of depression assessed in the DSM criteria for MDD on a 0-3 scale. Minimum score = 0 (no depression). Maximum scores = 21 (worst depression)

Outcome measures

Measure	Medication Management Group n=208 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Behavioral Activation Therapy n=208 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.
Depressive Symptom Severity as Measured by the Patient Health Questionnaire (PHQ-9) Depression Scale Results at 6 Months Follow up PHQ-9 at Baseline	14.31 score on a scale Standard Deviation 3.60	14.54 score on a scale Standard Deviation 3.45
Depressive Symptom Severity as Measured by the Patient Health Questionnaire (PHQ-9) Depression Scale Results at 6 Months Follow up PHQ-9 at 6 months	8.09 score on a scale Standard Deviation 6.06	7.53 score on a scale Standard Deviation 5.74

SECONDARY outcome

Timeframe: 3 month, 6 month, and 12 months from baseline enrollment

Population: Intention to treat: We analyzed all participants in both arms who were randomized to their respective intervention

The SF-12v2 is a 12-item questionnaire used to assess Health-related Quality of Life (HRQoL) from the patient's perspective. The SF-12v2 consists of 12 questions from the SF-36 that evaluate the same eight health domains: physical function, the role-physical, bodily pain, general health, vitality, social function, the role-emotional, and mental health. The Physical Component Summary (PCS) and Mental Component Summary (MCS) scores are norm-based scores ranging from 0 to 100 calculated from the responses to the 12 questions using scoring software from QualityMetric.com. In the general US population, the mean normal score is 50, with a standard deviation (SD) of 10. Higher scores indicate better outcomes with better HRQoL. Health-related Quality of Life - Physical Health as measured by SF-12 physical component and Health

Outcome measures

Measure	Medication Management Group n=208 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Behavioral Activation Therapy n=208 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results SF-12v2 Physical Component Score at Baseline	35.56 score on a scale Standard Deviation 7.74	35.89 score on a scale Standard Deviation 9.26
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results SF-12v2 Physical Component Score at 3-months	37.46 score on a scale Standard Deviation 10.17	37.69 score on a scale Standard Deviation 10.60
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results SF-12v2 Physical Component Score at 6-months	37.12 score on a scale Standard Deviation 10.99	38.82 score on a scale Standard Deviation 11.09
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results SF-12v2 Physical Component Score at 12-months	37.72 score on a scale Standard Deviation 10.81	37.89 score on a scale Standard Deviation 11.74
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results SF-12v2 MentalComponent Score at Baseline	37.22 score on a scale Standard Deviation 9.23	36.87 score on a scale Standard Deviation 9.16
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results SF-12v2 Mental Component Score at 3-months	47.63 score on a scale Standard Deviation 10.77	48.25 score on a scale Standard Deviation 11.08
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results SF-12v2 Mental Component Score at 6-months	46.85 score on a scale Standard Deviation 12.55	47.33 score on a scale Standard Deviation 10.97
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results SF-12v2 Mental Component Score at 12-months	47.41 score on a scale Standard Deviation 12.07	47.04 score on a scale Standard Deviation 9.91

SECONDARY outcome

Timeframe: 3 month, 6 month, and 12 months from baseline enrollment

Population: Intention to treat: We analyzed all participants in both arms who were randomized to their respective intervention

The KCCQ is a 23-item, self-administered instrument that quantifies 6 domains and yields 2 summary scores. The 6 domains are physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The 2 summary scores are the Clinical Summary Score and the Overall Summary Score. The Clinical Summary score includes total symptom and physical function scores to correspond with NYHA Classification. The Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores. Domain scores and summary scores are scaled from the raw item scores using a software available from the authors (SPERTUSJ@UMKC.EDU) to a range from 0 (worst) to 100 (best), in which higher scores reflect better heart-failure-specific quality of life and health status. Heart failure-specific quality of life are measured by the KCCQ Overall Summary Score and the Clinical Summary Score .

Outcome measures

Measure	Medication Management Group n=208 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Behavioral Activation Therapy n=208 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.
Change From Baseline on the Kansas City Cardiomyopathy Questionnaire (KCCQ ) Scale Results. KCCQ Overall Summary Score at 3-months	60.57 score on a scale Standard Deviation 23.03	62.03 score on a scale Standard Deviation 25.69
Change From Baseline on the Kansas City Cardiomyopathy Questionnaire (KCCQ ) Scale Results. KCCQ Overall Summary Score at 6-months	61.43 score on a scale Standard Deviation 24.48	64.35 score on a scale Standard Deviation 26.89
Change From Baseline on the Kansas City Cardiomyopathy Questionnaire (KCCQ ) Scale Results. KCCQ Overall Summary Score at 12-months	65.48 score on a scale Standard Deviation 24.83	63.24 score on a scale Standard Deviation 25.88
Change From Baseline on the Kansas City Cardiomyopathy Questionnaire (KCCQ ) Scale Results. KCCQ Clinical Summary Score at 3-months	64.16 score on a scale Standard Deviation 24.88	64.01 score on a scale Standard Deviation 26.76
Change From Baseline on the Kansas City Cardiomyopathy Questionnaire (KCCQ ) Scale Results. KCCQ Clinical Summary Score at 6-months	63.39 score on a scale Standard Deviation 25.92	66.15 score on a scale Standard Deviation 27.17
Change From Baseline on the Kansas City Cardiomyopathy Questionnaire (KCCQ ) Scale Results. KCCQ Clinical Summary Score at 12-months	67.02 score on a scale Standard Deviation 24.43	64.00 score on a scale Standard Deviation 27.19

SECONDARY outcome

Timeframe: 3 month, 6 month, and 12 months from baseline enrollment

Population: The number analyzed in each row differs from the overall number analyzed because of missing caregiver questionnaire data at each timepoint of 3-months, 6-months, and 12-months

The Caregiver Burden Questionnaire - Heart Failure Version 3.0 (CBQ-HF) is a quantitative survey of 26 questions covering the past four weeks of the caregiver's experience is evaluated as caregiver burden. The scale uses a 5-point Likert severity scale (Not at all=0, A little=1, Somewhat=2, Quite a lot=3, A lot=4) assessing 4 domains of physical, emotional/psychological, social and lifestyle burdens. The score is summed from all the questions for each domain, and then summed to a total score that ranges from 0 (no burden) to 104 (worst burden), in which higher scores reflect worse outcomes of higher burden on the caregiver. We will measure the caregiver burden measured by the CBQ-HF.

Outcome measures

Measure	Medication Management Group n=35 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Behavioral Activation Therapy n=43 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.
Change From Baseline on the Caregiver Burden Questionnaire-Heart Failure (CBQ-HF) Scale Results. CBQ-HF Overall Score at Baseline	68.06 score on a scale Standard Deviation 20.04	65.14 score on a scale Standard Deviation 20.96
Change From Baseline on the Caregiver Burden Questionnaire-Heart Failure (CBQ-HF) Scale Results. CBQ-HF Overall Score at 3-months	61.52 score on a scale Standard Deviation 19.72	57.70 score on a scale Standard Deviation 21.62
Change From Baseline on the Caregiver Burden Questionnaire-Heart Failure (CBQ-HF) Scale Results. CBQ-HF Overall Score at 6-months	57.38 score on a scale Standard Deviation 17.96	55.27 score on a scale Standard Deviation 18.13
Change From Baseline on the Caregiver Burden Questionnaire-Heart Failure (CBQ-HF) Scale Results. CBQ-HF Overall Score at 12-months	63.19 score on a scale Standard Deviation 23.63	60.39 score on a scale Standard Deviation 24.98

SECONDARY outcome

Timeframe: 3 month, 6 month, and 12 months from baseline enrollment

Population: Using a Zero Inflated Poisson (ZIP) Model, at 3, 6, and 12 months, the mean ratios of ED visits were compared for patients with heart failure who received BA to those who received MEDS.

We recorded the number of emergency department visits.

Outcome measures

Measure	Medication Management Group n=208 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Behavioral Activation Therapy n=208 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.
Mean Number of Emergency Department Visits Mean ED visits at 3-months	0.90 Mean ED visits Interval 0.0 to 1.0	0.55 Mean ED visits Interval 0.0 to 1.0
Mean Number of Emergency Department Visits Mean ED visits at 6-months	1.51 Mean ED visits Interval 0.0 to 2.0	1.31 Mean ED visits Interval 0.0 to 2.0
Mean Number of Emergency Department Visits Means ED visits at 12-months	2.43 Mean ED visits Interval 0.0 to 3.0	1.87 Mean ED visits Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: 3 month, 6 month, and 12 months from baseline enrollment

Population: Using a Zero Inflated Poisson (ZIP) Model, at 3, 6, and 12 months, the mean ratios of Hospital Admissions were compared for patients with heart failure who received BA to those who received MEDS.

We recorded the number of readmissions to the hospital.

Outcome measures

Measure	Medication Management Group n=208 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Behavioral Activation Therapy n=208 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.
Mean Number of Readmissions (Hospitalization) Mean Hospital Readmissions at 3-months	0.86 Mean Hospital Readmissions Interval 0.0 to 1.0	0.67 Mean Hospital Readmissions Interval 0.0 to 1.0
Mean Number of Readmissions (Hospitalization) Mean Hospital Readmissions at 6-months	1.48 Mean Hospital Readmissions Interval 0.0 to 2.0	1.30 Mean Hospital Readmissions Interval 0.0 to 2.0
Mean Number of Readmissions (Hospitalization) Mean Hospital Readmissions at 12-months	2.20 Mean Hospital Readmissions Interval 0.0 to 3.0	2.00 Mean Hospital Readmissions Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: 3 month, 6 month, and 12 months from baseline enrollment

Population: Using a Zero Inflated Poisson (ZIP) Model, the ratio of means were compared for total days in the hospital for BA vs. MEDS, at 3, 6, and 12 months respectively.

We recorded the number of total days in the hospital if they were hospitalized.

Outcome measures

Measure	Medication Management Group n=208 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Behavioral Activation Therapy n=208 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.
If Hospitalized, Mean Number of Total Days in the Hospital Mean Number of Total Days in the Hospital at 12-months	15.19 Mean Number ofTotal Days in the Hospital Interval 0.0 to 16.0	11.11 Mean Number ofTotal Days in the Hospital Interval 0.0 to 16.0
If Hospitalized, Mean Number of Total Days in the Hospital Mean Number of Total Days in the Hospital at 3-months	5.50 Mean Number ofTotal Days in the Hospital Interval 0.0 to 6.0	3.84 Mean Number ofTotal Days in the Hospital Interval 0.0 to 6.0
If Hospitalized, Mean Number of Total Days in the Hospital Mean Number of Total Days in the Hospital at 6-months	8.79 Mean Number ofTotal Days in the Hospital Interval 0.0 to 9.0	7.18 Mean Number ofTotal Days in the Hospital Interval 0.0 to 9.0

SECONDARY outcome

Timeframe: 3 month, 6 month, and 12 months from baseline enrollment

We recorded mortality data on the patients.

Outcome measures

Measure	Medication Management Group n=208 Participants The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Behavioral Activation Therapy n=208 Participants BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.
Mortality Was Also Measured Total Number of Deaths at 3-months	16 Participants	7 Participants
Mortality Was Also Measured Total Number of Deaths at 6-months	24 Participants	15 Participants
Mortality Was Also Measured Total Number of Deaths at 12-months	36 Participants	27 Participants

Adverse Events

Patients: Medication Management (MEDS)

Serious events: 36 serious events

Other events: 0 other events

Deaths: 36 deaths

Patients: Behavioral Activation Therapy (BA)

Serious events: 27 serious events

Other events: 0 other events

Deaths: 27 deaths

Serious adverse events

Measure	Patients: Medication Management (MEDS) n=208 participants at risk The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Medication Management: Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter. Caregivers did not receive active treatment, however they were assessed for caregiver burden using the Caregiver Burden Questionnaire at 3, 6, and 12 months.	Patients: Behavioral Activation Therapy (BA) n=208 participants at risk BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Behavioral Activation Therapy: The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement. Caregivers did not receive active treatment, however they were assessed for caregiver burden using the Caregiver Burden Questionnaire at 3, 6, and 12 months.
General disorders All-Cause Mortality	17.3% 36/208 • Number of events 36 • 1 year We collected information about all-cause mortality, serious adverse events, and other adverse events, using a standardized data collection form and summary form where a description of the event was provided. All-cause mortality, serious adverse events, and other (not including serious) adverse events were not monitored/assessed for caregivers. Adverse events were monitored/assessed without regard to the specific adverse event term.	13.0% 27/208 • Number of events 27 • 1 year We collected information about all-cause mortality, serious adverse events, and other adverse events, using a standardized data collection form and summary form where a description of the event was provided. All-cause mortality, serious adverse events, and other (not including serious) adverse events were not monitored/assessed for caregivers. Adverse events were monitored/assessed without regard to the specific adverse event term.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Waguih IsHak

Cedars-Sinai Medical Center

Phone: 310-423-3515

Email: Waguih.IsHak@cshs.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place