Trial Outcomes & Findings for Neurobiological Underpinnings of Placebo Response in Depression (NCT NCT02562430)

Last Updated: 2026-05-14

Results Overview

The HAM-D-32 (Hamilton Depression Rating Scale) scores can range between 0 and 124, with higher scores indicating more severe depression. Total score was reported here.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

76 participants

Primary outcome timeframe

8 weeks

Results posted on

2026-05-14

Participant Flow

In phase 1, participants were randomized to placebo or Wellbutrin XL for 4 weeks. Then, in Phase 2, participants that received placebo in Phase 1 were randomized again to either placebo or Wellbutrin XL, while participants that received Wellbutrin XL in Phase 1 continued Wellbutrin XL for another 4 weeks.

Participant milestones

Participant milestones
Measure	Active Treatment (Phase 1 and 2) This includes participants who received Bupropion XL in phase 1 and phase 2 of the study. 12.5 % of eligible participants were randomized to this group in phase 1 of the study.	Placebo (Phase 1 and 2) This group consisted of participants who were randomized to the placebo group during phase 1 and phase 2 of the study. 87.5% of eligible participants were randomized to receive placebo in phase 1 of the study.	Placebo (Phase 1), Active Treatment (Phase 2) This group consisted of participants who were randomized to the placebo group during phase 1 of the study, and then were randomized to receive Bupropion XL during the second phase of the study. 87.5% of eligible participants were randomized to receive placebo in phase 1 of the study.
Phase 1 STARTED	10	7	59
Phase 1 COMPLETED	9	7	52
Phase 1 NOT COMPLETED	1	0	7
Phase 2 STARTED	9	7	52
Phase 2 COMPLETED	8	3	46
Phase 2 NOT COMPLETED	1	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Treatment (Phase 1 and 2) This includes participants who received Bupropion XL in phase 1 and phase 2 of the study. 12.5 % of eligible participants were randomized to this group in phase 1 of the study.	Placebo (Phase 1 and 2) This group consisted of participants who were randomized to the placebo group during phase 1 and phase 2 of the study. 87.5% of eligible participants were randomized to receive placebo in phase 1 of the study.	Placebo (Phase 1), Active Treatment (Phase 2) This group consisted of participants who were randomized to the placebo group during phase 1 of the study, and then were randomized to receive Bupropion XL during the second phase of the study. 87.5% of eligible participants were randomized to receive placebo in phase 1 of the study.
Phase 1 Lost to Follow-up	0	0	4
Phase 1 Withdrawal by Subject	1	0	2
Phase 1 Medication Change: No longer eligible	0	0	1
Phase 2 Adverse Event	0	0	1
Phase 2 Lack of Efficacy	0	1	1
Phase 2 Lost to Follow-up	0	1	4
Phase 2 Physician Decision	1	1	0
Phase 2 Withdrawal by Subject	0	1	0

Baseline Characteristics

Four participants in the placebo group did not report their age.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Treatment (Phase 1 and 2) n=10 Participants This includes participants who received Bupropion XL in phase 1 and phase 2 of the study. 12.5 % of eligible participants were randomized to this group in phase 1 of the study.	Placebo (Phase 1 and 2) n=7 Participants This group consisted of participants who were randomized to the placebo group during phase 1 and phase 2 of the study. 87.5% of eligible participants were randomized to receive placebo in phase 1 of the study.	Placebo (Phase 1) to Active Treatment (Phase 2) n=48 Participants This group consisted of participants who were randomized to the placebo group during phase 1 of the study, and then were randomized to receive Bupropion XL during the second phase of the study. 87.5% of eligible participants were randomized to receive placebo in phase 1 of the study.	Total n=65 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=1512 Participants • Four participants in the placebo group did not report their age.	0 Participants n=504 Participants • Four participants in the placebo group did not report their age.	3 Participants n=2016 Participants • Four participants in the placebo group did not report their age.	3 Participants n=99 Participants • Four participants in the placebo group did not report their age.
Age, Categorical Between 18 and 65 years	10 Participants n=1512 Participants • Four participants in the placebo group did not report their age.	7 Participants n=504 Participants • Four participants in the placebo group did not report their age.	45 Participants n=2016 Participants • Four participants in the placebo group did not report their age.	62 Participants n=99 Participants • Four participants in the placebo group did not report their age.
Age, Categorical >=65 years	0 Participants n=1512 Participants • Four participants in the placebo group did not report their age.	0 Participants n=504 Participants • Four participants in the placebo group did not report their age.	0 Participants n=2016 Participants • Four participants in the placebo group did not report their age.	0 Participants n=99 Participants • Four participants in the placebo group did not report their age.
Sex: Female, Male Female	4 Participants n=1512 Participants • Four participants in the placebo group at baseline did not report gender.	4 Participants n=504 Participants • Four participants in the placebo group at baseline did not report gender.	26 Participants n=2016 Participants • Four participants in the placebo group at baseline did not report gender.	34 Participants n=99 Participants • Four participants in the placebo group at baseline did not report gender.
Sex: Female, Male Male	6 Participants n=1512 Participants • Four participants in the placebo group at baseline did not report gender.	3 Participants n=504 Participants • Four participants in the placebo group at baseline did not report gender.	22 Participants n=2016 Participants • Four participants in the placebo group at baseline did not report gender.	31 Participants n=99 Participants • Four participants in the placebo group at baseline did not report gender.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=1512 Participants	0 Participants n=504 Participants	1 Participants n=2016 Participants	1 Participants n=99 Participants
Race (NIH/OMB) Asian	2 Participants n=1512 Participants	0 Participants n=504 Participants	5 Participants n=2016 Participants	7 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=1512 Participants	0 Participants n=504 Participants	1 Participants n=2016 Participants	1 Participants n=99 Participants
Race (NIH/OMB) Black or African American	1 Participants n=1512 Participants	1 Participants n=504 Participants	3 Participants n=2016 Participants	5 Participants n=99 Participants
Race (NIH/OMB) White	7 Participants n=1512 Participants	5 Participants n=504 Participants	33 Participants n=2016 Participants	45 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=1512 Participants	0 Participants n=504 Participants	3 Participants n=2016 Participants	3 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=1512 Participants	1 Participants n=504 Participants	2 Participants n=2016 Participants	3 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=1512 Participants	0 Participants n=504 Participants	10 Participants n=2016 Participants	10 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=1512 Participants	7 Participants n=504 Participants	37 Participants n=2016 Participants	53 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=1512 Participants	0 Participants n=504 Participants	1 Participants n=2016 Participants	2 Participants n=99 Participants
HAM-D 32	23.38 Total score STANDARD_DEVIATION 11.77 • n=1512 Participants	23.96 Total score STANDARD_DEVIATION 11.66 • n=504 Participants	23.71 Total score STANDARD_DEVIATION 11.73 • n=2016 Participants	23.38 Total score STANDARD_DEVIATION 11.77 • n=99 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: This analysis includes all participants who completed the final study visit (visit 10, 8 weeks after baseline).

The HAM-D-32 (Hamilton Depression Rating Scale) scores can range between 0 and 124, with higher scores indicating more severe depression. Total score was reported here.

Outcome measures

Outcome measures
Measure	Phase 1: Active Treatment n=8 Participants This includes participants who received Bupropion XL in phase 1 of the study. 12.5 % of eligible participants were randomized to this group in phase 1 of the study.	Phase 1: Placebo n=50 Participants This group consisted of participants who were randomized to the placebo group during phase 1 of the study. 87.5% of eligible participants were randomized to receive placebo in phase 1 of the study.	Phase 2: Active Treatment n=12 Participants This group consisted of participants who were randomized to receive Bupropion XL in phase 1 and phase 2 of the study, and participants who were randomized to receive placebo during phase 1 of the study, and then were randomized to receive Bupropion XL during phase 2 of the study.	Phase 2: Placebo n=46 Participants This group consisted of participants who were randomized to receive placebo in phase 1 and phase 2 of the study.
HAM-D 32	33.2 Total score Standard Deviation 8.6	16.50 Total score Standard Deviation 8.6	16.00 Total score Standard Deviation 8.6	16.7 Total score Standard Deviation 8.6

Adverse Events

Phase 1: Active Treatment

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase 1: Placebo

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Phase 2: Active Treatment

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Phase 2: Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Cristina Cusin

Massachusetts General Hospital

Phone: 617-724-5510

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase 1: Active Treatment n=10 participants at risk This includes participants who received Bupropion XL in phase 1 of the study. 12.5 % of eligible participants were randomized to this group in phase 1 of the study.	Phase 1: Placebo n=59 participants at risk This group consisted of participants who were randomized to the placebo group during phase 1 of the study. 87.5% of eligible participants were randomized to receive placebo in phase 1 of the study.	Phase 2: Active Treatment n=62 participants at risk This group consisted of participants who were randomized to receive Bupropion XL in phase 1 and phase 2 of the study, and participants who were randomized to receive placebo during phase 1 of the study, and then were randomized to receive Bupropion XL during phase 2 of the study.	Phase 2: Placebo n=7 participants at risk This group consisted of participants who were randomized to receive placebo in phase 1 and phase 2 of the study.
Gastrointestinal disorders Increased appetite	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/59 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/62 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Nervous system disorders Headache/Migraine	10.0% 1/10 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	11.9% 7/59 • Number of events 9 • All events from the enrollment to discontinuation or study completion (at week 8).	8.1% 5/62 • Number of events 5 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Nervous system disorders Auditory/visual sensory changes	10.0% 1/10 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/59 • All events from the enrollment to discontinuation or study completion (at week 8).	1.6% 1/62 • Number of events 3 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Psychiatric disorders Insomnia (any type, incl. middle insomnia)	10.0% 1/10 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	5.1% 3/59 • Number of events 3 • All events from the enrollment to discontinuation or study completion (at week 8).	6.5% 4/62 • Number of events 9 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Psychiatric disorders Anxiety / panic / restlessness	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	1.7% 1/59 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	3.2% 2/62 • Number of events 2 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Psychiatric disorders Mood swings	10.0% 1/10 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/59 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/62 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
General disorders Fatigue / increased fatigue	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	1.7% 1/59 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	1.6% 1/62 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	14.3% 1/7 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).
Musculoskeletal and connective tissue disorders Lower back pain	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/59 • All events from the enrollment to discontinuation or study completion (at week 8).	4.8% 3/62 • Number of events 4 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	6.8% 4/59 • Number of events 5 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/62 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Infections and infestations Upper Respiratory Infection	10.0% 1/10 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	3.4% 2/59 • Number of events 3 • All events from the enrollment to discontinuation or study completion (at week 8).	4.8% 3/62 • Number of events 3 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Infections and infestations Folliculitis	10.0% 1/10 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/59 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/62 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Social circumstances Increased stress due to family emergency	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	1.7% 1/59 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/62 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Social circumstances Car accident sequelae	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	1.7% 1/59 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/62 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Surgical and medical procedures Self-catheterization	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/59 • All events from the enrollment to discontinuation or study completion (at week 8).	1.6% 1/62 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Gastrointestinal disorders Constipation	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	1.7% 1/59 • All events from the enrollment to discontinuation or study completion (at week 8).	9.7% 6/62 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Gastrointestinal disorders Nausea	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/59 • All events from the enrollment to discontinuation or study completion (at week 8).	4.8% 3/62 • Number of events 3 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Gastrointestinal disorders Diarrhea	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	1.7% 1/59 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	1.6% 1/62 • Number of events 2 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).
Gastrointestinal disorders Lack of appetite / decreased appetite	0.00% 0/10 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/59 • All events from the enrollment to discontinuation or study completion (at week 8).	1.6% 1/62 • Number of events 1 • All events from the enrollment to discontinuation or study completion (at week 8).	0.00% 0/7 • All events from the enrollment to discontinuation or study completion (at week 8).