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Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment in Major Depressive Disorder.

This study has been completed.
Sponsor:
Collaborator:
Shire
Information provided by (Responsible Party):
J. Alexander Bodkin, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01148979
First received: June 21, 2010
Last updated: April 19, 2017
Last verified: April 2017
  Purpose
This study aims to test the effect of a newly-approved stimulant medication, lisdexamfetamine dimesylate (Vyvanse), on specific residual symptoms of depression found in some patients who are undergoing treatment with, but have only partially responded to, a selective-serotonin reuptake inhibitor (SSRI) or selective-norepinephrine reuptake inhibitor (SNRI) antidepressant. Specifically, the investigators hypothesize that symptoms potentially related to deficient dopaminergic activity, such as lassitude, apathy, reduced positive affect and impaired executive function, in particular, will improve. This protocol is designed to test the hypothesis that this cluster of co-occurring residual symptoms sometimes found in treated depression will respond as a group to adjunctive psychostimulant therapy. The investigators propose to demonstrate this cluster of residual depressive symptoms and to measure the effect of stimulant therapy on it. The investigators hope to better understand the specific symptoms in this clinical population that are likely to improve with stimulant therapy.

Condition Intervention Phase
Major Depressive Disorder
Drug: Lisdexamfetamine Dimesylate (Vyvanse)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
This is a double-blind, placebo-controlled, crossover study in which each subject will act as their own control after being randomly assigned to placebo or Lisdexamfetamine Dimesylate (Vyvanse) for the first 4 weeks of study treatment, then receiving the other for the second 4 weeks of treatment. The two 4-week treatment periods are separated by a washout of 2 weeks.
Masking: Participant, Investigator
Masking Description:
Both the study participant and the study investigators making evaluations are blinded to which treatment arm the participants are assigned to (i.e., whether they are receiving placebo or Vyvanse at any given point). Placebo and active medication capsules look identical.
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo-Controlled, Randomized Trial of Adjunctive Lisdexamfetamine Dimesylate in Residual Symptoms of Major Depressive Disorder Partially Responsive to Selective Serotonin or Norepinephrine Reuptake Inhibitor Monotherapy

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Change From Baseline in the Dysphoric Apathy/Retardation Sub-factor (MDAR) of Montgomery-Asberg Depression Rating Scale (MADRS) at 4 Weeks. [ Time Frame: Baseline to 4 weeks of treatment ]
    The Montgomery-Asberg Depression Rating Scale Dysphoric Apathy Retardation subfactor (MDAR) is a 5-item subscale of the clinician-administered 10-item Montgomery-Asberg Depression Rating Scale (MADRS). MDAR score can range from 0-30 with a higher score representing a greater severity of depressive symptoms.


Enrollment: 35
Study Start Date: September 2010
Study Completion Date: October 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adjunct Lisdexamfetamine (Vyvanse)
Participants receive Lisdexamfetamine Dimesylate 20-50 mg capsule each morning for 4 weeks. After a washout period of 2 weeks, they receive Placebo capsule (matching Lisdexamfetamine Dimesylate (Vyvanse) capsule) each morning for 4 weeks.
Drug: Lisdexamfetamine Dimesylate (Vyvanse)
Lisdexamfetamine Dimesylate (Vyvanse) capsules dose ranging from 20mg to 50 mg.
Other Name: Vyvanse
Placebo Comparator: Adjunct Placebo
Participants receive Placebo capsule (matching Lisdexamfetamine Dimesylate (Vyvanse) 20-50 mg capsule) each morning for 4 weeks. After a washout period of 2 weeks, they receive Lisdexamfetamine Dimesylate capsule each morning for 4 weeks.
Drug: Placebo
Lisdexamfetamine Dimesylate (Vyvanse)-matched placebo capsules.
Other Name: Sugar pill

Detailed Description:
This protocol is designed to test the hypothesis that a cluster of co-occurring residual symptoms sometimes found in treated depression will respond as a group to psychostimulant therapy. This cluster includes apathy, reduced drive, fatigue, impaired executive function and other cognitive measures, and low positive affect. We propose to measure this cluster of symptoms in a population of residually depressed subjects demonstrating them, and then to measure the effect of stimulant therapy on this cluster, and each constituent symptom, as well as to measure its effect on subjects' overall functional impairment, and to document treatment emergent adverse effects. The goal is to gather data about the response of these residual symptoms to stimulant therapy. Since each subject will be exposed to active treatment and matched placebo, a benefit to individual participants will be to learn if their specific symptom burden is ameliorated by stimulant therapy, and what adverse effects may emerge for them. We hope to develop an understanding of the specific symptoms in this clinical population that are likely to improve with stimulant therapy. We also hope to be able to characterize the side effect burden of stimulant therapy in this clinical population.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Meeting diagnostic criteria for major depression during the present episode of illness, currently with at least mild improvement by report (CGI-I ≥3) but with continuing residual symptoms.
  2. A score of ≥10 on MADRS items 1,2,6,7 and 8, (the MADRS Dysphoric Apathy/Retardation factor, Parker et al., 2003) at screening and randomization. These 5 items are: Apparent sadness, Reported sadness, Concentration difficulties, Lassitude, and Inability to feel. A score of ≥3 will be required for at least 2 of these items.
  3. A score of 3 or 4 on the Clinical Global Impression of Severity (CGI-S) at screening and randomization.
  4. At randomization subjects must have received therapeutic dosages of approved SSRI or SNRI agents for at least 8 weeks, with the last 4 weeks at a constant dosage.
  5. Females of Child-bearing Potential (FOCP) must have a negative serum beta Human Chorionic Gonadotropin (B-hCG) pregnancy test at the screening visit and a negative urine pregnancy test at the baseline visit, and agree to use one of the following methods of birth control: oral contraceptives, contraceptive implants, injectable contraceptives, IUDs, double-barrier contraception, sexual abstinence or vasectomized partner(s).

Exclusion Criteria:

  1. Treatment within 4 weeks of randomization with any non-SSRI/SNRI antidepressant (trazodone is permitted up to 100 mg at night for sleep); any antipsychotic agent; any mood stabilizer; any standing benzodiazepine regimen other than at low doses for sleep (≤ 1 mg lorazepam HS or the equivalent); or a standing regimen of any other agent that may affect cognitive function (e.g., psychostimulants, including modafinil or R-modafinil).
  2. Any current or past psychotic disorder, Bipolar I or II disorder, Current panic disorder, History of ADHD, Antisocial Personality Disorder or Borderline Personality Disorder, Mental retardation or any dementing disorder.
  3. Covi Anxiety Scale score greater than Raskin Depression Scale score at Screening, to exclude subjects with more prominent anxiety than depression
  4. MADRS Sleep (item 4), or Appetite (item 5) >3 at screening or randomization
  5. Initial insomnia at screening that is not adequately controlled by sleep medication (trazodone up to 100 mg HS for sleep and/or ≤ 1 mg lorazepam HS or the equivalent).
  6. Medical conditions that might be exacerbated by Vyvanse treatment, such as uncontrolled hypertension or angina; or conditions that would make study findings hard to interpret, such as hyperthyroidism
  7. History of seizure (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or family history of Tourette's Disorder.
  8. Known cardiac structural abnormality or any other condition that may affect cardiac performance
  9. Any clinically significant ECG or laboratory abnormality at Screening
  10. Current abnormal thyroid function, as defined by abnormal TSH at Screening (Treatment with a stable dose of thyroid medication for at least 3 months is permitted if TSH is normal at screening).
  11. Suicide attempt within the past 2 years or a history of any homicidal behavior.
  12. MADRS Suicidal thoughts (item 10) >4 at any study visit, or if a patient is considered by the investigator to be at clinical risk of suicide at any time in the course of the study.
  13. resting sitting systolic blood pressure >149mmHg or diastolic blood pressure > 95mmHg. Subjects may be on monotherapy with anti-hypertensive medication.
  14. documented allergy, hypersensitivity, intolerance, or non-responsivity to methylphenidate or amphetamines.
  15. Subject has a history of a substance use disorder (abuse or dependence, as defined by DSM-IV-TR™), with the exception of nicotine dependence, within 6 months prior to screening.
  16. Subject has glaucoma
  17. Subject is taking other medications that have central nervous system (CNS) effects or affect performance, such as sedating antihistamines and decongestant
  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: NCT01148979

Locations
United States, Massachusetts
McLean Hospital
Belmont, Massachusetts, United States, 02478
Sponsors and Collaborators
Mclean Hospital
Shire
Investigators
Principal Investigator: J. Alexander Bodkin Bodkin, MD Mclean Hospital
  More Information

Publications:

Responsible Party: J. Alexander Bodkin, Director, Clinical Psychopharmacology Research Program, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01148979     History of Changes
Other Study ID Numbers: 2010-P-000871
Study First Received: June 21, 2010
Results First Received: March 8, 2017
Last Updated: April 19, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Mclean Hospital:
Major Depressive Disorder
Cognitive Impairment
Partial Response
Residual Symptoms

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depressive Disorder, Major
Cognition Disorders
Mood Disorders
Mental Disorders
Neurocognitive Disorders
Depression
Pathologic Processes
Behavioral Symptoms
Lisdexamfetamine Dimesylate
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on May 23, 2017