Stimulant Enhancement of Well-Being Therapy for Depression

Major Depressive Disorder Clinical Trial

Official title:

Stimulant Enhancement of Well-Being Therapy for Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01478113
• Other study ID #: 2011P002148
• Secondary ID: 2011D002171
• Status: Recruiting
• Phase: N/A
• First received: September 26, 2011
• Last updated: September 17, 2012
• Start date: February 2012
• Est. completion date: January 2014

Study information

• Verified date: September 2012
• Source: Massachusetts General Hospital
• Contact: Max Martinson, BS
• Phone: 617-726-8727
• Email: mmartinson[@]partners.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria

1. Outpatients between 18 and 60 years of age.

2. Experiencing residual symptoms after 8 weeks of SSRI therapy, with at least 4 weeks at a stable dose of the current agent prior to randomization.

3. Fulfillment of DSM-IV diagnostic criteria for MDD during the present episode of illness with continuing residual symptoms.

4. A score of 14 to 26 on the 31-item Hamilton Depression Rating Scale (HAM-D-31) at screening and randomization.

5. A Clinical Global Impression of Severity (CGI-S) score of 3 or 4 at screening and randomization.

Exclusion Criteria

1. Treatment within 4 weeks of randomization with any non-SSRI antidepressant, antipsychotic, mood stabilizer, standing benzodiazepine, stimulant, or stimulant-like agent.

1. Allowed exception 1: Concomitant benzodiazepines, at a stable dose, that have been taken for at least one year with no history of abuse.

2. Allowed exception 2: Effexor, duloxetine (Cymbalta) or milnacipran (Savella) can serve as main SSRI treatment.

3. Allowed exception 3: Combinations of SSRIs (ex. Zoloft & Lexapro concomitantly) are acceptable as main SSRI treatment.

2. If a subject endorses "yes" or "agree" of any item from 12 to 23 on the CHRT, it would indicate active suicidality and would be exclusionary.

3. Significant suicide risk.

4. Current treatment-resistant episode of MDD.

5. A primary diagnosis of an Axis I disorder other than MDD.

6. History of a psychotic disorder, dysthymia, antisocial personality disorder, BPD, or mental retardation.

7. History of a substance use disorder, with the exception of nicotine dependence, within 12 months prior to screening.

8. History of stimulant abuse, prescription drug abuse, and eating disorders.

9. Initial insomnia at screening that is not adequately controlled by medications. Subjects with recent history of unstable insomnia as defined by active or poorly controlled symptoms of insomnia within the past 1 month will be excluded.

10. Co-morbid medical conditions including a structural heart defect or rhythm abnormality that might be exacerbated by stimulant therapy; hypertension as measured by a resting sitting systolic blood pressure of > 149mmHg or diastolic blood pressure > 95mmHg; tachycardia as measured by a sitting pulse rate of >100 bpm or <50 bpm after resting for 5 minutes.

11. Allergy, hypersensitivity, intolerance, or history of non-responsivity to stimulant medications.

12. History of non-responsivity to CBT or well-being therapy.

13. Women who are pregnant or breastfeeding.

14. Glaucoma or hyperthyroidism

15. Current concomitant therapy is only permitted if it is supportive therapy (not specifically CBT) and has been ongoing for at least one year. However, if a subject has been in therapy for less than one year and wishes to discontinue or take a hiatus from their current therapy before coming in for a screening visit, this will be allowed. Additionally, subjects may not enter into other talk therapies for the duration of this study.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Amphetamine-dextroamphetamine (AMPH)
The amphetamine-dextroamphetamine will be in a pill formulation. The dosage of the amphetamine-dextroamphetamine will be flexibly adjusted up or down by a study clinician based on the 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.
• Placebo
The placebo will match the dextroamphetamine in form, dosage, frequency, and duration.

Behavioral:
• Well-being therapy
Therapy sessions will last between 30-50 minutes. The sessions will take place at every visit after the screening visit.

Locations

Country	Name	City	State
United States	Depression Clinical and Research Program	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
David P. Soskin,M.D.	Harvard University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hamilton-Depression Rating Scale(SIGH-D)-17 items	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.	Baseline and visit 11/week 8 of treatment, or between baseline and early termination visit.	No
Primary	Change in Hamilton-Depression Rating Scale(SIGH-D)-31 item	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.	Baseline to Visit 11 (which is week 8 of treatment) or Early Termination Visit.	No
Secondary	Change in Psychological Well-being Scale (PWB)	Well-being improvement: Comparison between the 2 groups of changes on the PWB at Baseline and Visit 11/Early Termination.	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	No
Secondary	Change in the Snaith-Hamilton Pleasure Scale (SHAPS)	Improvement of anhedonia: Comparison between the 2 groups of changes on the SHAPS at Baseline and Visit 11/Early Termination.	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	No
Secondary	Change in Behavioral inhibition/activation scale (BIS/BAS)	Improvement of deficits in behavioral activation: Comparison between the 2 groups of changes on the BIS/BAS at Baseline and Visit 11/Early Termination.	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	No
Secondary	Change in Positive and Negative Affective Scale (PANAS)	Improvement of deficits in positive affectivity: Comparison between the 2 groups of changes on the PANAS at Baseline and Visit 11/Early Termination.	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	No
Secondary	Change in functioning on Short Form-12(SF-12)	Functional improvement: Comparison between the 2 groups of changes on the SF-12 scale at Baseline and Visit 11/Early termination visit.	Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.	No