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

Phase 4

Terminated

Conditions: Depression

Interventions: Drug: Pramipexole

Registration Number: NCT01066897

Lead Sponsor: Stanford University

Brief Summary: We hope to learn how a brain circuit that is important to the understanding of depression, anhedonia and positive affect responds to a novel pharmaceutical treatment for depression and related symptoms. Adults who have a diagnosis of major depression and are not completely responsive to antidepressant medication will be sought out for participation; as will an equal number of adults not suffering from the disorder. Those suffering from depression will be given pramipexole, an investigational medication for eight weeks during which information will be collected about mood, cognition, and brain function. Adults not suffering from depression will also be evaluated with these measures.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Must meet DSM-IV criteria for Major Depressive Disorder
HAM-D score >18 on a 21-item assessment at eligibility
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).
20-55 years of age

Exclusion Criteria

Substance abuse in the past 6 months
ECT in the past 6 months
On a MAOI, tricyclic antidepressant, lithium, an antipsychotic, thyroid augmentation, 2 antidepressants simultaneously or lamotrigine
History of any psychosis including psychotic depression
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
History of compulsive gambling
Pregnant females or females of childbearing years not using adequate birth control in the opinion of the investigators
Known sensitivity to Pramipexole
Significant suicide risk in the opinion of the investigators
Significant medical conditions that would preclude safe participation in the study in the opinion of the investigators
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.)
Significant abnormalities are observed in screening laboratory evaluation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pramipexole	Pramipexole	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Discontinued Study Due to Side-effects of the Medication	throughout the 8 weeks
% Change in Hamilton Depression Rating Scale From Baseline to week8	Baseline and weeks 8	Utilized the Hamilton Depression Rating Scale, 21-item version to assess depressive symptoms, with a range of 0-63. Higher scores equals more depression. For the change score, where higher equals greater improvement in depressive symptoms. Healthy controls were not utilized in this analysis, as no week 8 ratings for health controls were obtained.
Change in Mesolimbic Reward System Activity From Pre to Post Treatment (8 Weeks)	baseline and Week 8	Because of the limited number of depressed patients who completed the study (n=5) and noisy/unusable imaging data at various time points, this data was unable to be examined.

Secondary Outcome Measures

Name	Time	Method
Mesolimibic Reward Activity Baseline Differences in Depression vs Healthy Controls	Baseline	Because of the small number of depressed patients and noisy/unusable data, analyses were not run.