Imaging Dopamine Release in Depression
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Pramipexole
Intervention description: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day.
Intervention MeSH terms: Pramipexole
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Major depressive disorder; MDD; depression; pramipexole

Summary:

      This study aims to determine whether ventral striatal dopamine release is a mechanism of
      reward motivation in major depression, whether dopamine release is low in depression, and
      whether DA release and reward motivation predict response to dopamine-targeted treatment with
      pramipexole.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Weight between 44 kg and 115 kg

          -  Meets DSM-IV criteria for principal diagnosis of MDD, current major depressive
             episode, without psychotic features

          -  Score of >16 and <29 on 17-item Hamilton Rating Scale for Depression

          -  Psychotropic-naïve, as defined by lifetime <2 weeks treatment with antidepressants,
             anxiolytics or antipsychotics

          -  Able to tolerate a treatment-free period during study participation

          -  Able to provide informed consent

        Exclusion Criteria:

          -  A principal diagnosis of any current Axis I psychiatric disorder other than the MDD

          -  Lifetime diagnosis of any psychotic disorder, bipolar disorder, mental retardation,
             attention deficit/hyperactivity disorder, or substance use disorders (including
             nicotine use disorders)

          -  Serious suicidal risk or history of violent behavior which would make participation in
             the protocol unsafe

          -  Any tobacco use in the prior three months (if not already excluded for
             abuse/dependence by #1)

          -  Illicit drug use in the prior three months, as evidenced by history or urine
             toxicology screen

          -  Women who are pregnant, nursing, postmenopausal, or using hormonal methods of birth
             control

          -  Women who are not using an effective birth control method or sexual abstinence during
             the ten days before the scan

          -  Any medical or neurological problem that might affect interpretation of findings or
             safety of participation (e.g., blood dyscrasias, lymphomas, hypersplenism,
             endocrinopathies, renal failure or chronic obstructive lung disease, malignancy,
             neurological diseases of the brain, history of seizures or head trauma), low
             hemoglobin (Hb < 12 gm/dL in males, Hb < 10.5 gm/dL in females))

          -  Blood donation within 4 weeks of study

          -  Metal implants or paramagnetic objects in the body that might affect safety of
             undergoing MRI (e.g., heart pacemaker, shrapnel, bullets, surgical prostheses or
             surgical clips), as determined in consultation with a neuroradiologist and according
             to the guidelines set forth in the reference: "Guide to MR procedures and metallic
             objects" Shellock; Lippincott Williams and Wilkins, NY, 2001

          -  More than one major risk factor for coronary artery disease (e.g. hyperlipidemia,
             sedentary lifestyle). Smokers are already excluded by #4 above, and diabetics by #8
             above

          -  Systolic blood pressure > 140 or diastolic blood pressure > 90 based on at least two
             readings at rest

          -  History of untoward reaction to amphetamine or other stimulant medication, or
             pramipexole

          -  Any psychotropic treatment in the past 3 weeks (or depot medication in the past 6
             months), except for lorazepam,which may be administered as needed prior to imaging day

          -  Current, past or anticipated exposure to radiation in the workplace, or participation
             in nuclear medicine procedures, including research protocols (In case of previous
             exposure to activity due to research studies, subjects will be eligible if all
             conditions listed below are fulfilled: 1) The injected dose and dosimetry of the
             radiotracer are known; 2) Except for research studies, the subject has not been
             exposed to radiation (workplace and medical); 3) Adding prior exposure to the exposure
             due to the study will result in a yearly cumulative exposure lower than the FDA limit
             for research studies

          -  Family history of schizophrenia in parents, siblings, or children

          -  Ongoing cognitive-behavioral or interpersonal psychotherapy for depression (Supportive
             therapy is not an exclusion)

          -  Ongoing treatment with cimetidine