Depression
Conditions
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.
Interventions
DRUGPramipexole
Patients will received increasing dose of pramipexole
Sponsors
National Alliance for Research on Schizophrenia and Depression
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Pramipexole: Patients will received increasing dose of pramipexole | 7 |
| Healthy Controls Non depressed, non treatment comparison group from baseline | 9 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | stopped study after developing the flu. | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Pramipexole | Total | Healthy Controls |
|---|---|---|---|
| Age, Continuous | 44.00 years STANDARD_DEVIATION 14.12 | 38.81 years STANDARD_DEVIATION 14.41 | 34.78 years STANDARD_DEVIATION 14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 12 Participants | 5 Participants |
| Region of Enrollment United States | 7 Participants | 16 Participants | 9 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
% 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.
Time frame: Baseline and weeks 8
Population: For two drop outs, used LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole | % Change in Hamilton Depression Rating Scale From Baseline to week8 | .46 percentage reduction in depression score | Standard Deviation 0.42 |
Comparison: For the 2 dropouts, used LOCF.p-value: 0.067t-test, 2 sided
Primary
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.
Time frame: baseline and Week 8
Population: 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.
Primary
Number of Participants Who Discontinued Study Due to Side-effects of the Medication
Time frame: throughout the 8 weeks
Population: \# of participants who dropped out due to medication side-effects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pramipexole | Number of Participants Who Discontinued Study Due to Side-effects of the Medication | 2 Participants |
| Healthy Controls Who Did Not Take Medication | Number of Participants Who Discontinued Study Due to Side-effects of the Medication | 0 Participants |
p-value: 0.002Chi-squared
Secondary
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.
Time frame: Baseline
Population: Because of the small number of depressed patients and noisy/unusable data, analyses were not run.