Stimulant Enhancement of Well-Being Therapy for Depression

Not Applicable

Terminated

Conditions: Major Depressive Disorder

Interventions: Drug: Amphetamine/dextroamphetamine
Drug: Placebo
Behavioral: Well-being therapy

Registration Number: NCT01478113

Lead Sponsor: Massachusetts General Hospital

Brief Summary: This study aims to identify a novel enhancement strategy for residual symptoms of major depressive disorder (MDD) Dopamine (DA) has been viewed as a "pleasure neurotransmitter" for over 30 years. Yet recent data from animal and human studies suggest that dopamine has greater effects on "wanting" than on "liking." Therefore, the investigators of this study have hypothesized that amphetamine/d-amphetamine (AMPH), a medication which increases dopamine transmission in the reward centers of the brain, may have a more powerful antidepressant effect in combination with well-being therapy (WBT), a specific type of cognitive-behavioral therapy, which helps individuals with depression to increase their contact with natural rewards and decrease reward-interfering thoughts.

The investigators will test their hypothesis by randomizing 40 individuals with residual symptoms of depression, already taking an antidepressant that affects serotonin (e.g. Prozac, Paxil), to 8 weeks of treatment with either WBT in combination with AMPH, or WBT with pill placebo. The effectiveness of each treatment will be measured using a reliable scale, called the Hamilton Depression Rating Scale.

The investigators have also hypothesized that people assigned to the stimulant/WBT group will have greater improvements in functioning, well-being, and positive affectivity than those the people assigned to the WBT/placebo group.

Detailed Description: The study will have 11 visits occur over 8 weeks with study visits scheduled weekly or biweekly.

Detailed Description:

The study visit occurrences are as follows:

1. Week 0- Screening Visit

2. Week 1- Baseline Visit

3. Week 2- one phone visit and one clinic visit in one week

4. Week 3- one phone visit and one clinic visit in one week

5. Week 4- one visit in one week

6. Week 5- one visit in one week

7. Week 6- one visit in one week

8. Week 7- one visit in one week

9. Week 8- one visit in one week

WBT description Four licensed therapists, who have been trained and certified in WBT, will provide weekly sessions of 30 to 50 minutes in duration. Therapists will follow the procedures outlined in the WBT manual. The initial sessions (weeks 0-2) will be focused on identifying and contextualizing episodes of well-being. The intermediate sessions (weeks 3-5) will be focused on modifying cognitions and behaviors, which lead to premature interruption of well-being, and optimizing cognitions and behaviors, which have been idiographically linked to enhanced well-being. Final sessions (weeks 6-8) will apply the Psychological Well-Being scales (PWB) to refine treatment according to Ryff's dimensions of well-being. Additional principles and techniques of WBT include reappraisal, mood-charting, scheduling of activities, shaping, problem-solving, and assertiveness training.

Medication Schedule Participants will receive treatment with the stimulant, amphetamine/d-amphetamine, or matched placebo.

Participants will start at 1 pill (placebo or 5 mg amphetamine/d-amphetamine) in the morning and 1 pill (placebo or 5 mg amphetamine/d-amphetamine) at noon. The treatment will then be flexibly adjusted up or down by a study clinician based on participant's response. Dose ranges will be 1-3 pills (placebo or 5 mg amphetamine) in the morning and 1-3 pills (placebo or 5 mg amphetamine) at noon.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
WBT + amphetamine/dextroamphetamine	Amphetamine/dextroamphetamine	In the active group, participants will receive treatment with Well-being therapy and amphetamine-dextroamphetamine.
WBT + amphetamine/dextroamphetamine	Well-being therapy	In the active group, participants will receive treatment with Well-being therapy and amphetamine-dextroamphetamine.
WBT + placebo	Placebo	In the placebo group, participants will receive treatment with Well-being therapy and pill placebo.
WBT + placebo	Well-being therapy	In the placebo group, participants will receive treatment with Well-being therapy and pill placebo.

Primary Outcome Measures

Name	Time	Method
Change in Hamilton-Depression Rating Scale(SIGH-D)-17 Items	Baseline and visit 11/week 8 of treatment, or between baseline and early termination visit.	Comparison between the 2 groups of the percentage of subjects in remission, as defined by a HAM-D-17 score of \< 8 at endpoint visit 11/week 8 of treatment, or early termination visit.
Change in Hamilton-Depression Rating Scale(SIGH-D)-31 Item	Baseline to Visit 11 (which is week 8 of treatment) or Early Termination Visit.	Comparison between the 2 groups of the percentage of participants who have responded to the treatment (response is defined here as a 50% or greater improvement on the HAM-D-31 score) between Baseline and Visit 11 or Early Termination Visit.

Secondary Outcome Measures

Name	Time	Method
Change in Functioning on Short Form-12(SF-12)	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	Functional improvement: Comparison between the 2 groups of changes on the SF-12 scale at Baseline and Visit 11/Early termination visit.
Change in Psychological Well-being Scale (PWB)	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	Well-being improvement: Comparison between the 2 groups of changes on the PWB at Baseline and Visit 11/Early Termination.
Change in the Snaith-Hamilton Pleasure Scale (SHAPS)	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	Improvement of anhedonia: Comparison between the 2 groups of changes on the SHAPS at Baseline and Visit 11/Early Termination.
Change in Behavioral Inhibition/Activation Scale (BIS/BAS)	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	Improvement of deficits in behavioral activation: Comparison between the 2 groups of changes on the BIS/BAS at Baseline and Visit 11/Early Termination.
Change in Positive and Negative Affective Scale (PANAS)	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	Improvement of deficits in positive affectivity: Comparison between the 2 groups of changes on the PANAS at Baseline and Visit 11/Early Termination.