Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment in Major Depressive Disorder.
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Lisdexamfetamine Dimesylate (Vyvanse); Placebo
Intervention description: Lisdexamfetamine Dimesylate (Vyvanse) capsules dose ranging from 20mg to 50 mg.; Lisdexamfetamine Dimesylate (Vyvanse)-matched placebo capsules.
Intervention MeSH terms: Lisdexamfetamine Dimesylate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
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: Double (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.
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Major Depressive Disorder; Cognitive Impairment; Partial Response; Residual Symptoms

Summary:

      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.
    

Eligibility 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