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

• Intolerable side effects occur [ Time Frame: throughout the 8 weeks ] [ Designated as safety issue: Yes ]
  
• Hamilton Depression Rating Scale [ Time Frame: 8 weeks: > 50% reduction in score from baseline ] [ Designated as safety issue: Yes ]
  

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.