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

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.

Study Overview

• Status: Terminated
• Conditions: Depression
• Intervention / Treatment: Drug: Pramipexole

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Pramipexole; Patients will received increasing dose of pramipexole
No Intervention: Healthy Controls; Non depressed, non-intervention comparison group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline and weeks 8
Change in Mesolimbic Reward System Activity From Pre to Post Treatment (8 Weeks)	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.	baseline and Week 8

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Alliance for Research on Schizophrenia and Depression
• Investigators: Principal Investigator: Jennifer Keller, Stanford University

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: February 9, 2010
• First Submitted That Met QC Criteria: February 9, 2010
• First Posted (Estimate): February 10, 2010

Study Record Updates

• Last Update Posted (Actual): May 16, 2017
• Last Update Submitted That Met QC Criteria: April 11, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: SU-02042010-4902; 17847