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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Mclean Hospital
Sponsor:
Collaborator:
Shire
Information provided by (Responsible Party):
J. Alexander Bodkin, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01148979
First received: June 21, 2010
Last updated: March 2, 2014
Last verified: March 2014
  Purpose

This study aims to test the effect of a newly-approved stimulant medication, lisdexamfetamine (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 psychostimulant therapy. The investigators 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 investigators hope to better understand the specific symptoms in this clinical population that are likely to improve with stimulant therapy. The investigators also hope to be able to characterize the side effect burden of stimulant therapy in this clinical population.


Condition Intervention Phase
Major Depressive Disorder
Drug: Lisdexamfetamine Dimesylate 20-50 mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo-Controlled, Randomized Trial of Adjunctive, Flexibly-Dosed Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment In Major Depressive Disorder (MDD) Partially Responsive to Selective Serotonin Reuptake Inhibitor (SSRI) or Selective Norepinephrine Reuptake Inhibitor (SNRI) Monotherapy

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Change in the dysphoric apathy/retardation sub-factor of Montgomery-Asberg Depression Rating Scale (MADRS). [ Time Frame: Weekly, from Baseline to week 4 of treatment ] [ Designated as safety issue: No ]
    The study's Primary endpoint will be the change in the dysphoric apathy/retardation sub-factor of Montgomery-Asberg Depression Rating Scale (MADRS), to be administered at every visit.


Estimated Enrollment: 40
Study Start Date: September 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar Pill Drug: Lisdexamfetamine Dimesylate 20-50 mg

Subjects given 30 mg study drug (Vyvanse vs. matched placebo) at baseline to take each morning. If 30 mg intolerable before next scheduled appointment, they can return to clinic and exchange 30 mg tablets for 20 mg tablets. Visit 3 dosage range is 20-40 mg/d. Now subjects have been taking either 30 or 20 mg of study medication per day. If clinical effects insufficient and side effects tolerable, subject's dose will be raised by 10 mg/d to 30 or 40 mg/d. If subjects receiving more than 20 mg/d experience uncomfortable side effects, their dose may be reduced to 20 mg at that visit. Visit 4 dosage range is 20-50 mg, study drug dose may be moved up or down by 10 mg based on clinical judgment, minimum of 20 mg, maximum of 50 mg/d. Study drug dosage must not change over the last 2 weeks (end of 4 weeks on study drug).

Arms: Sugar Pill , Lisdexamfetamine Dimesylate 20-50mg Other Names:
 Vyvanse

Other Name: Vyvanse
Experimental: Lisdexamfetamine Dimesylate 20-50mg Drug: Lisdexamfetamine Dimesylate 20-50 mg

Subjects given 30 mg study drug (Vyvanse vs. matched placebo) at baseline to take each morning. If 30 mg intolerable before next scheduled appointment, they can return to clinic and exchange 30 mg tablets for 20 mg tablets. Visit 3 dosage range is 20-40 mg/d. Now subjects have been taking either 30 or 20 mg of study medication per day. If clinical effects insufficient and side effects tolerable, subject's dose will be raised by 10 mg/d to 30 or 40 mg/d. If subjects receiving more than 20 mg/d experience uncomfortable side effects, their dose may be reduced to 20 mg at that visit. Visit 4 dosage range is 20-50 mg, study drug dose may be moved up or down by 10 mg based on clinical judgment, minimum of 20 mg, maximum of 50 mg/d. Study drug dosage must not change over the last 2 weeks (end of 4 weeks on study drug).

Arms: Sugar Pill , Lisdexamfetamine Dimesylate 20-50mg Other Names:
 Vyvanse

Other Name: Vyvanse

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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 HS 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.

    Covi Anxiety Scale score greater than Raskin Depression Scale score at Screening, to exclude subjects with more prominent anxiety than depression

  3. MADRS Sleep (item 4), or Appetite (item 5) >3 at screening or randomization
  4. 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).
  5. 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
  6. History of seizure (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or family history of Tourette's Disorder.
  7. Known cardiac structural abnormality or any other condition that may affect cardiac performance
  8. Any clinically significant ECG or laboratory abnormality at Screening
  9. 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).
  10. Suicide attempt within the past 2 years or a history of any homicidal behavior.
  11. 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.
  12. resting sitting systolic blood pressure >149mmHg or diastolic blood pressure > 95mmHg. Subjects may be on monotherapy with anti-hypertensive medication.
  13. documented allergy, hypersensitivity, intolerance, or non-responsivity to methylphenidate or amphetamines.
  14. 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.
  15. Subject has glaucoma
  16. 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

Contacts
Contact: J. Alexander Bodkin, MD 617-855-3186 abodkin@mclean.harvard.edu

Locations
United States, Massachusetts
McLean Hospital Recruiting
Belmont, Massachusetts, United States, 02478
Contact: J. Alexander Bodkin, MD    617-855-3186    abodkin@mclean.harvard.edu   
Principal Investigator: J. Alexander Bodkin, MD         
Sponsors and Collaborators
Mclean Hospital
Shire
Investigators
Principal Investigator: J. Alexander Bodkin Bodkin, MD Mclean Hospital
  More Information

No publications provided

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
Last Updated: March 2, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Cognition Disorders
Depressive Disorder
Depressive Disorder, Major
Disease
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Mood Disorders
Depression
Behavioral Symptoms
Pathologic Processes
Dextroamphetamine
Serotonin Uptake Inhibitors
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Serotonin Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014