Stimulant Enhancement of Well-Being Therapy for Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Massachusetts General Hospital
Sponsor:
Collaborator:
Harvard University
Information provided by (Responsible Party):
David P. Soskin,M.D., Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01478113
First received: September 26, 2011
Last updated: September 17, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention
Major Depressive Disorder
Drug: Amphetamine-dextroamphetamine (AMPH)
Drug: Placebo
Behavioral: Well-being therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Stimulant Enhancement of Well-Being Therapy for Depression

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in Hamilton-Depression Rating Scale(SIGH-D)-17 items [ Time Frame: Baseline and visit 11/week 8 of treatment, or between baseline and early termination visit. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Visit 11 (which is week 8 of treatment) or Early Termination Visit. ] [ Designated as safety issue: No ]
    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:
  • Change in Psychological Well-being Scale (PWB) [ Time Frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit. ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit. ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit. ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit. ] [ Designated as safety issue: No ]
    Improvement of deficits in positive affectivity: Comparison between the 2 groups of changes on the PANAS at Baseline and Visit 11/Early Termination.

  • Change in functioning on Short Form-12(SF-12) [ Time Frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit. ] [ Designated as safety issue: No ]
    Functional improvement: Comparison between the 2 groups of changes on the SF-12 scale at Baseline and Visit 11/Early termination visit.


Estimated Enrollment: 40
Study Start Date: February 2012
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Well-being therapy with amphetamine/dextroamphetamine
In the active group, participants will receive treatment with Well-being therapy and amphetamine-dextroamphetamine.
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.
Other Names:
  • Adderall
  • Adderall XR
Behavioral: Well-being therapy
Therapy sessions will last between 30-50 minutes. The sessions will take place at every visit after the screening visit.
Other Names:
  • Well-being therapy
  • WBT
Placebo Comparator: Well-being therapy with placebo
In the placebo group, participants will receive treatment with Well-being therapy and pill placebo.
Drug: Placebo
The placebo will match the dextroamphetamine in form, dosage, frequency, and duration.
Other Names:
  • Placebo
  • Sugar-pill
Behavioral: Well-being therapy
Therapy sessions will last between 30-50 minutes. The sessions will take place at every visit after the screening visit.
Other Names:
  • Well-being therapy
  • WBT

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478113

Contacts
Contact: Max Martinson, BS 617-726-8727 mmartinson@partners.org
Contact: David Soskin, MD 617-643-0877 dsoskin@partners.org

Locations
United States, Massachusetts
Depression Clinical and Research Program Recruiting
Boston, Massachusetts, United States, 02114
Contact: Max Martinson, BS    617-726-8727    mmartinson@partners.org   
Contact: David Soskin, MD    617-643-0877    dsoskin@partners.org   
Principal Investigator: Maurizio Fava, MD         
Principal Investigator: David Soskin, MD         
Sponsors and Collaborators
David P. Soskin,M.D.
Harvard University
Investigators
Principal Investigator: Maurizio Fava, MD Massachusetts General Hospital and Harvard Medical School
Principal Investigator: David Soskin, MD Massachusetts General Hospital and Harvard Medical School
  More Information

No publications provided

Responsible Party: David P. Soskin,M.D., Staff Psychiatrist, Depression Clinical & Research Program (DCRP), Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01478113     History of Changes
Other Study ID Numbers: 2011P002148, 2011D002171
Study First Received: September 26, 2011
Last Updated: September 17, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Major Depressive Disorder
Therapy
Medication study
Depression
Therapy study

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Amphetamine
Central Nervous System Stimulants
Dextroamphetamine
Adderall
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Dopamine Uptake Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014