Stimulant Enhancement of Well-Being Therapy for Depression

NCT01478113 | Terminated Results

• 2 other identifiers: 2011P0021482011D002171
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; Therapy; Medication study; Depression; Therapy study

Outcome Measures

Primary Outcomes (2)

• 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.

• 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.

Secondary Outcomes (5)

• Change in Psychological Well-being Scale (PWB)

  Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.

• Change in the Snaith-Hamilton Pleasure Scale (SHAPS)

  Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.

• Change in Behavioral Inhibition/Activation Scale (BIS/BAS)

  Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.

• Change in Positive and Negative Affective Scale (PANAS)

  Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.

• Change in Functioning on Short Form-12(SF-12)

  Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.

Study Arms (2)

WBT + amphetamine/dextroamphetamine

ACTIVE COMPARATOR

In the active group, participants will receive treatment with Well-being therapy and amphetamine-dextroamphetamine.

Drug: Amphetamine/dextroamphetamine; Behavioral: Well-being therapy

WBT + placebo

PLACEBO COMPARATOR

In the placebo group, participants will receive treatment with Well-being therapy and pill placebo.

Drug: Placebo; Behavioral: Well-being therapy

Interventions

Amphetamine/dextroamphetamine DRUG

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.

Also known as: Adderall, Adderall XR

WBT + amphetamine/dextroamphetamine

Placebo DRUG

The placebo will match the dextroamphetamine in form, dosage, frequency, and duration.

Also known as: Sugar-pill

WBT + placebo

Well-being therapy BEHAVIORAL

Therapy sessions will last between 30-50 minutes. The sessions will take place at every visit after the screening visit.

Also known as: WBT

WBT + amphetamine/dextroamphetamine; WBT + placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Outpatients between 18 and 60 years of age.
• 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.
• Fulfillment of DSM-IV diagnostic criteria for MDD during the present episode of illness with continuing residual symptoms.
• A score of 14 to 26 on the 31-item Hamilton Depression Rating Scale (HAM-D-31) at screening and randomization.
• A Clinical Global Impression of Severity (CGI-S) score of 3 or 4 at screening and randomization.

You may not qualify if:

• Treatment within 4 weeks of randomization with any non-SSRI antidepressant, antipsychotic, mood stabilizer, standing benzodiazepine, stimulant, or stimulant-like agent.
• Allowed exception 1: Concomitant benzodiazepines, at a stable dose, that have been taken for at least one year with no history of abuse.
• Allowed exception 2: Effexor, duloxetine (Cymbalta) or milnacipran (Savella) can serve as main SSRI treatment.
• Allowed exception 3: Combinations of SSRIs (ex. Zoloft \& Lexapro concomitantly) are acceptable as main SSRI treatment.
• Significant suicide risk.
• Current treatment-resistant episode of MDD.
• A primary diagnosis of an Axis I disorder other than MDD.
• History of a psychotic disorder, dysthymia, antisocial personality disorder, BPD, or mental retardation.
• History of a substance use disorder, with the exception of nicotine dependence, within 12 months prior to screening.
• History of stimulant abuse, prescription drug abuse, and eating disorders.
• 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.
• 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.
• Allergy, hypersensitivity, intolerance, or history of non-responsivity to stimulant medications.
• History of non-responsivity to CBT or well-being therapy.
• Women who are pregnant or breastfeeding.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Harvard Medical School (HMS and HSDM): collaborator

Study Sites (1)

Depression Clinical and Research Program

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

SLI381; Adderall

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Limitations and Caveats

This study was shut down due to original PI leaving the institution and due to lack of continued funding. As such, we were not able to enroll a sufficient number of patients to analyze data/answer study hypothesis/achieve study aims.

Results Point of Contact

• Title: Maren Nyer
• Organization: Massachusetts General Hospital

mnyer@partners.org

617-643-4897

Study Officials

• Maurizio Fava, MD

  Massachusetts General Hospital and Harvard Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Psychologist

Study Record Dates

• First Submitted: September 26, 2011
• First Posted: November 23, 2011
• Study Start: February 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2015
• Last Updated: April 26, 2017
• Results First Posted: April 26, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)