Imaging the Nucleus Accumbens in Major Depressed Patients 'Treated With Pramipexole

Patients who meet DSM-IV criteria for major depression(using the SCID),have a Hamilton
Depression Rating Scale score of at least 18, and who are not complete responders to
antidepressant medications will be invited to participate in an open label study with
pramipexole. Patients who are not complete responders to an adequate trial of an
antidepressant (see inclusion criteria below) will be openly treated with pramipexole for 8
weeks. Participants must be between the ages of 20-55 and will include both men and women.
Patient's mood will be assessed each visit using the Hamilton Depression (HDRS) and will
also complete a series of questionnaires. This will include the physical and social
anhedonia scales (Chapman et al., 1976; Eckblad et al., 1982), the Snaith-Hamilton Pleasure
Scale (SHAPS; Franken et al., 2007; Snaith et al., 1995), the Mood and Anxiety Symptom
Questionnaire Short Form (MASQ; Watson, Weber, et al., 1995; Watson, Clark, et al., 1995),
and the Positive and Negative Affect Scale (Watson & Clark, 1991)among others. No other
adjunctive agents will be allowed during the eight weeks of the study. Patients will be seen
for four weeks on a weekly basis, then biweekly thereafter.

Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg
three times a day for the second week, and 0.5 mg three times a day for the third week. The
dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a
target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1)
achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2)
intolerable side effects; or 3) completion of the 8-week study. Participants will be seen
weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia
will assessed at each visit.

Depressed participants will also undergo functional MRI and neuropsychological testing
twice, once at baseline and once after completion of the medication. 20 healthy control
subjects with no history of Axis I disorders and who score less than 5 on the HDRS will
participate in the baseline MRI, neuropsychological testing, and clinical
ratings/questionnaires.

Inclusion Criteria:

1. Must meet DSM-IV criteria for Major Depressive Disorder

2. HAM-D score >18 on a 21-item assessment at eligibility

3. On at least an adequate dose of fluoxetine (40 mg/day), paroxetine (40 mg/day)
paroxetine CR (50mg), sertraline (150 mg/day), citalopram (40 mg/day), escitalopram
(20 mg/day), venlafaxine (150 mg/day), mirtazapine (30 mg/day), or duloxetine (60
mg/day) for at least 6 weeks (monotherapy).

4. 20-55 years of age

Exclusion Criteria:

1. Substance abuse in the past 6 months

2. ECT in the past 6 months

3. On a MAOI, tricyclic antidepressant, lithium, an antipsychotic, thyroid augmentation,
2 antidepressants simultaneously or lamotrigine

4. History of any psychosis including psychotic depression

5. History of Bipolar I, Bipolar II, or Bipolar NOS illness, or concurrent symptoms of
mania or hypomania that do not meet the criteria for any bipolar disorder

6. History of compulsive gambling

7. Pregnant females or females of childbearing years not using adequate birth control in
the opinion of the investigators

8. Known sensitivity to Pramipexole

9. Significant suicide risk in the opinion of the investigators

10. Significant medical conditions that would preclude safe participation in the study in
the opinion of the investigators

11. Psychoactive drugs other than one of the antidepressants listed on Inclusion criteria
#4. (A non-barbiturate sedative or hypnotic or benzodiazepine such as trazodone
50mg/day, zolpidem 10mg/day, lorazepam 3mg/day or clonazepam 2mg/day will be allowed
if it has been in use for at least 1 month prior to the baseline visit.)

12. Significant abnormalities are observed in screening laboratory evaluation.