Trial Outcomes & Findings for Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits (NCT NCT04352101)

Last Updated: 2023-12-29

Results Overview

Targeted FC is calculated as the degree of correlation in activity between a 3mm3 radius sphere in VS and the vmPFC cluster identified as being reward-sensitive in neuroimaging meta-analyses and as used to define vmPFC in previous work. Subject-level correlations for degree of vmPFC-VS FC is Fisher's Z transformed {Z(R)=0.5ln\[(1+R)/(1-R)\]}, a standard method for calculating fMRI functional connectivity, whereby greater Z-scores reflected stronger correlated functional magnetic resonance imaging (fMRI) activity (i.e., higher VS-vmPFC connectivity). For each study timepoint, Z-scores will be extracted and the change in mean FC values compared to baseline will be calculated. The central value is 0, and the standard deviation depends on the sample variance. Increasing values indicate increasing connectivity between the indicated brain regions (VS and vmPFC). There are no relevant thresholds, and there is no direct interpretation of results in terms of clinical improvement.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

18 participants

Primary outcome timeframe

Baseline, Week 4, Week 8

Results posted on

2023-12-29

Participant Flow

Participants were recruited from the Emory Clinic in Atlanta, Georgia, USA. Participant enrollment began September 23, 2020 and the final follow-up assessment occurred July 25, 2022.

Participant milestones

Participant milestones
Measure	Bupropion Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion extended release (XL) for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Overall Study STARTED	10	8
Overall Study COMPLETED	8	7
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Bupropion Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion extended release (XL) for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Overall Study Physician Decision	2	1

Baseline Characteristics

Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bupropion n=10 Participants Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram n=8 Participants Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.	Total n=18 Participants Total of all reporting groups
Age, Continuous	39.6 years STANDARD_DEVIATION 10.0 • n=5 Participants	41.5 years STANDARD_DEVIATION 10.3 • n=7 Participants	40.4 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4, Week 8

Population: This analysis includes participants with available and analyzable fMRI scans both at baseline and post-treatment.

Outcome measures

Outcome measures
Measure	Bupropion n=7 Participants Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram n=5 Participants Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Change in Targeted Ventromedial Prefrontal Cortex-Ventral Striatal (vmPFC-VS) Functional Connectivity (FC) Baseline to Week 4	0.02 Z-score Standard Deviation 0.14	-0.13 Z-score Standard Deviation 0.16
Change in Targeted Ventromedial Prefrontal Cortex-Ventral Striatal (vmPFC-VS) Functional Connectivity (FC) Baseline to Week 8	0.02 Z-score Standard Deviation 0.20	0.09 Z-score Standard Deviation 0.19

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 8

Population: One participant in the Bupropion group was excluded prior to completing this task, and another did not complete the task due to shoulder pain during the task. One participant in the Escitalopram group did not complete the task at the Week 4 visit because the visit was seen virtually (due to illness) and neuropsychological testing was not performed.

The Effort-Expenditure for Rewards Task (EEfRT) is a computer-based multi-trial game to assess motivation. Participants are given an opportunity to choose different task difficulty levels to obtain monetary rewards (easy tasks have low rewards while hard tasks have higher rewards). Each trial has a high, medium, or low probability of success, and this information is given to the participant when they are deciding between easy and hard tasks. The task lasts for 20 minutes, and first 50 trials are analyzed. The proportion of hard-task choices across each level of probability is calculated. Possible values range between 0 to1 with 1 being a better outcome indicating the mean probability of making a hard (high effort) choice. Lower proportions of hard task choices indicate decreased motivation.

Outcome measures

Outcome measures
Measure	Bupropion n=8 Participants Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram n=8 Participants Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Proportion of Hard-Task Choices During the Effort-Expenditure for Rewards Task (EEfRT) Baseline	0.392 proportion of hard-task choices Standard Deviation 0.257	0.450 proportion of hard-task choices Standard Deviation 0.290
Proportion of Hard-Task Choices During the Effort-Expenditure for Rewards Task (EEfRT) Week 2	0.450 proportion of hard-task choices Standard Deviation 0.316	0.385 proportion of hard-task choices Standard Deviation 0.275
Proportion of Hard-Task Choices During the Effort-Expenditure for Rewards Task (EEfRT) Week 4	0.348 proportion of hard-task choices Standard Deviation 0.207	0.321 proportion of hard-task choices Standard Deviation 0.215
Proportion of Hard-Task Choices During the Effort-Expenditure for Rewards Task (EEfRT) Week 8	0.360 proportion of hard-task choices Standard Deviation 0.229	0.323 proportion of hard-task choices Standard Deviation 0.158

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8

Population: This analysis includes participants who were still participating in the study at the indicated study visit.

The SHAPS-C is a 14-item clinician-administered scale assessing the amount of pleasure during common daily activities that the participant has experienced in the past week. Responses are given on a scale of 1 to 4 where 1 = lots of pleasure and 4 = no pleasure. Total scores range from 14 to 56 with lower scores indicating greater enjoyment of activities.

Outcome measures

Outcome measures
Measure	Bupropion n=10 Participants Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram n=8 Participants Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Snaith-Hamilton Pleasure Scale (SHAPS-C) Score Baseline	39.400 Score on a scale Standard Deviation 6.535	38.625 Score on a scale Standard Deviation 2.200
Snaith-Hamilton Pleasure Scale (SHAPS-C) Score Week 2	36.222 Score on a scale Standard Deviation 6.629	33.375 Score on a scale Standard Deviation 4.534
Snaith-Hamilton Pleasure Scale (SHAPS-C) Score Week 4	33.778 Score on a scale Standard Deviation 9.680	27.250 Score on a scale Standard Deviation 3.196
Snaith-Hamilton Pleasure Scale (SHAPS-C) Score Week 6	35.375 Score on a scale Standard Deviation 7.963	25.250 Score on a scale Standard Deviation 4.559
Snaith-Hamilton Pleasure Scale (SHAPS-C) Score Week 8	32.125 Score on a scale Standard Deviation 9.125	24.857 Score on a scale Standard Deviation 6.890

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8

Population: This analysis includes participants who were still participating in the study at the indicated study visit. One participant in the Bupropion group did not complete this assessment at the Week 4 visit.

The MAP-SR is an 18-item self-report inventory that has been validated in psychiatric populations and is designed to disentangle motivational and consummatory components of everyday activities over a 24-hr period. Responses are given on a 5-point scale where 0 = no pleasure or motivation and 4 = extreme pleasure or motivation. Total scores range from 0 to 72 and higher scores indicate greater motivation and pleasure during everyday activities.

Outcome measures

Outcome measures
Measure	Bupropion n=10 Participants Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram n=8 Participants Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Motivation and Pleasure Scale-Self-Report (MAP-SR) Score Baseline	27.800 Score on a scale Standard Deviation 7.829	28.000 Score on a scale Standard Deviation 8.211
Motivation and Pleasure Scale-Self-Report (MAP-SR) Score Week 2	29.333 Score on a scale Standard Deviation 8.846	34.875 Score on a scale Standard Deviation 8.493
Motivation and Pleasure Scale-Self-Report (MAP-SR) Score Week 4	35.250 Score on a scale Standard Deviation 9.254	42.500 Score on a scale Standard Deviation 11.199
Motivation and Pleasure Scale-Self-Report (MAP-SR) Score Week 6	37.250 Score on a scale Standard Deviation 8.876	44.750 Score on a scale Standard Deviation 9.852
Motivation and Pleasure Scale-Self-Report (MAP-SR) Score Week 8	38.000 Score on a scale Standard Deviation 10.529	45.714 Score on a scale Standard Deviation 9.232

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8

Population: This analysis includes participants who were still participating in the study at the indicated study visit.

The IDS-SR is a 30-item self-reported measurement of depression severity. Responses are given on a 4-point scale where 0 = no problems and 3 = severe problems. Total scores are based on 28 items and range from 0 to 84 with higher scores indicating more severe symptoms of depression.

Outcome measures

Outcome measures
Measure	Bupropion n=10 Participants Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram n=8 Participants Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Inventory of Depressive Symptomatology - Self-Report (IDS-SR) Baseline	38.800 Score on a scale Standard Deviation 9.942	42.250 Score on a scale Standard Deviation 7.906
Inventory of Depressive Symptomatology - Self-Report (IDS-SR) Week 2	30.222 Score on a scale Standard Deviation 8.729	30.250 Score on a scale Standard Deviation 9.407
Inventory of Depressive Symptomatology - Self-Report (IDS-SR) Week 4	23.556 Score on a scale Standard Deviation 11.577	21.500 Score on a scale Standard Deviation 9.258
Inventory of Depressive Symptomatology - Self-Report (IDS-SR) Week 6	25.000 Score on a scale Standard Deviation 11.464	16.250 Score on a scale Standard Deviation 11.235
Inventory of Depressive Symptomatology - Self-Report (IDS-SR) Week 8	23.875 Score on a scale Standard Deviation 11.532	18.143 Score on a scale Standard Deviation 12.734

Adverse Events

Bupropion

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Escitalopram

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Andrew H. Miller, MD

Emory University

Phone: 404-727-8260

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Bupropion n=10 participants at risk Participants randomized to take bupropion for 8 weeks. Participants took 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.	Escitalopram n=8 participants at risk Participants randomized to take escitalopram for 8 weeks. Participants took 10mg/d of escitalopram for two weeks, then the dose increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Endocrine disorders Nocturnal perspiration	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Skin and subcutaneous tissue disorders Itching	20.0% 2/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Lightheadedness	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Headache	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	12.5% 1/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Dry mouth	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Cardiac disorders Chest pain	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Vascular disorders High blood pressure	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Blood and lymphatic system disorders Enlarged lymph nodes	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Musculoskeletal and connective tissue disorders Pain in limb	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Psychiatric disorders Stress	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Insomnia	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Gastrointestinal disorders Nausea	20.0% 2/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	37.5% 3/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Vivid dreams	10.0% 1/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Psychiatric disorders Anxious mood	20.0% 2/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	0.00% 0/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Gastrointestinal disorders Diarrhea	0.00% 0/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	12.5% 1/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Sleep disturbance	0.00% 0/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	12.5% 1/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Fatigue	0.00% 0/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	25.0% 2/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Drowsiness	0.00% 0/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	12.5% 1/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Musculoskeletal and connective tissue disorders Tightness in jaw	0.00% 0/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	12.5% 1/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
General disorders Nightmares	0.00% 0/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	12.5% 1/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.
Reproductive system and breast disorders Decreased libido	0.00% 0/10 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.	12.5% 1/8 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 8.