Magnetic Resonance Imaging Study of Lisdexamfetamine for Bipolar Depression
Condition: Bipolar Depression
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder
Intervention: Lisdexamfetamine; Placebo
Intervention description: Start at 20 mg daily. Increased to a maximum of 40 mg daily. Can be decreased in 10 mg increments.; Subjects will receive placebo matched to lisdexamfetamine.
Intervention MeSH terms: Lisdexamfetamine Dimesylate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 2.0
Sex: All
Minimum age: 21 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: lisdexamfetamine; vyvanse; bipolar disorder; depression; stimulant; magnetic resonance spectroscopy; functional magnetic resonance imaging; neuropsychological testing

Summary:

      There have been reports that stimulants may be effective for bipolar depression without
      triggering mania. This study will examine whether lisdexamfetamine can improve depressive
      symptoms over the course of eight weeks. Lisdexamfetamine is a prodrug stimulant that is
      currently approved for attention deficit hyperactivity disorder (ADHD). Participants take the
      study drug or placebo in addition to a mood stabilizer. The study includes functional
      magnetic resonance imaging and magnetic resonance spectroscopy to determine whether the
      medication alters the response to affective stimuli or glutamate, glutamine, or gamma
      aminobutyric acid (GABA) levels. Neuropsychological testing is also included to determine
      whether the study drug improves memory and attention in this population. The primary
      hypothesis is that lisdexamfetamine is clinically effective in this population. The secondary
      hypothesis is that it will result in an increased response to affective stimuli and altered
      neurotransmitter levels in the anterior cingulate cortex.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged 21 to 50 years.

          -  Diagnosed with Bipolar Disorder I or II disorder.

          -  Currently in the depressive phase of the illness.

          -  Montgomery Asberg Depression Rating Scale (MADRS) score greater than 15.

          -  Medication regimen (Lamotrigine, Valproate, Lithium, either alone or in combination
             with atypical antipsychotics, or typical antipsychotics) at stable doses for at least
             one month.

          -  Has an established residence and phone.

          -  Capable of providing informed consent.

        Exclusion Criteria:

          -  Met Diagnostic and Statistical Manual 4th edition (DSM-IV-TR) criteria for rapid
             cycling within the 6 months prior to enrolling in the study.

          -  Meets DSM-IV-TR criteria for Schizophrenia, Schizoaffective disorder, Post-Traumatic
             Stress disorder, Obsessive-Compulsive disorder, or Eating disorder. Co-morbid anxiety
             disorders are not a reason for exclusion.

          -  History of psychotic symptoms at any point during the subject's illness.

          -  Met DSM-IV-TR criteria for alcohol or substance (except for nicotine) dependence or
             abuse within the past 6 months.

          -  Lifetime history of amphetamine abuse or dependence.

          -  Subject has a lifetime history of stimulant-induced mania

          -  History of seizures, including febrile seizures in childhood.

          -  Young Mania Rating Scale (YMRS) greater than 8.

          -  History of significant coronary artery disease, angina, untreated or inadequately
             treated thyroid disease (less than 1 month chemically euthyroid), type I diabetes,
             autoimmune disease, glaucoma, hypertension, seizures, or other medical condition(s)
             which in the opinion of the principal investigator is likely to significantly impact
             the subject's mood or potential response to the study medication.

          -  Electrocardiogram (ECG) with significant arrhythmias or conduction abnormalities,
             which in the opinion of the physician investigator preclude study participation;
             uncontrolled hypertension (>160/100) or tachycardia (heart rate >110).

          -  Female subjects who are peri or post-menopausal.

          -  Subjects taking Ritalin or other stimulants, theophylline, steroids, atomoxetine,
             cholinesterase inhibitors, memantine, modafinil, warfarin, anticonvulsants, clonidine,
             theophylline, monoamine oxidase inhibitors, and pseudoephedrine, or other medications
             that are likely to significantly interact (either pharmacokinetically or
             pharmacodynamically) with the subject's mood or Lisdexamfetamine.

          -  Subject regularly (more than 4 days per week) ingests more than four caffeine
             containing drinks per day.

          -  Pregnancy.

          -  In women of childbearing potential, an unwillingness to avoid pregnancy for the
             duration of the study.

          -  Active suicidal ideation.

          -  History of homicidal ideation.

          -  Allergy or other clinical condition which prohibits the use of all of the approved
             mood stabilizers or Lisdexamfetamine.

          -  Metal in the body (e.g. history of working as a sheet metal worker) or pacemaker which
             is a contra-indication to magnetic resonance imaging (MRI).

          -  Significant claustrophobia.