Bipolar Disorder, Major Depression
Conditions
Keywords
Bipolar, Depression, Mania, Hypomania, fMRI, antidepressant
Brief summary
The purpose of the study is to find out what parts of the brain have increased or decreased activity and connectivity in individuals who have bipolar disorder, major depression, or no history of mood disorder. Another purpose of this study is to use MRI images to determine which young adults with major depression may be at greater risk for developing mild or more severe symptoms of mania which suggests a diagnosis of bipolar disorder.
Detailed description
The study involves two phases, phase one includes the screening visit and MRI. The second phase, for depression participants, involves in person follow ups for up to two years. The second phase, for healthy and bipolar participants, involves phone follow ups, every three months for up to two years. The purpose of this study is listed above. We plan to enroll 200 participants total.
Interventions
Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.
Sponsors
The Cleveland Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
FOR BIPOLAR DEPRESSED PATIENTS: 1. Ages 15 - 30 years (inclusive) and able to give voluntary informed consent (parents must also sign consent for subjects under 18) 2. Satisfy criteria for Diagnostic and Statistical Manual 4th edition (DSM-IV-TR) for Bipolar I or II disorder 3. Satisfy criteria for DSM-IV depressive episode-current 4. 17-item Hamilton Depression Rating Scale \> 15 but \< 25; 5. Young Mania Rating Scale score \< 10 6. Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire. 7. Able to be managed as outpatients during the study as ascertained by the following - i. Clinical Global Severity Scale \< 5 i.e. moderately ill; ii. No significant suicidal or homicidal ideation or grossly disabled. INCLUSION CRITERIA FOR ALL UNIPOLAR DEPRESSED PATIENTS: 1. Ages 15 - 30 years and able to give voluntary informed consent (Parental consent must also be obtained for those under 18 years old). 2. Satisfy criteria for DSM-IV-TR Major Depressive Episode using a Structured Interview 3. Never met criteria for mania or hypomania 4. 17-item Hamilton Depression Rating Scale score (HDRS) \> 15 and \< 25. 5. Young Mania Rating Scale (YMRS) score \< 10 6. Satisfy safety criteria to undergo an MRI scan 7. Able to be managed as outpatients during the study as ascertained by the following - i. Clinical Global Severity Scale \< 5 i.e. moderately ill; ii. No significant suicidal or homicidal ideation or grossly disabled ADDITIONAL INCLUSION CRITERIA FOR HIGH RISK UD (HRUD) PATIENTS BESIDE THE INCLUSION CRITERIA FOR UD: At least one of the following: 1. Family history of bipolar disorder in at least one first degree relative 2. History of any sub-threshold hypomania symptoms 3. History of mood episode related psychotic symptoms ADDITIONAL INCLUSION CRITERIA FOR LOW RISK UD (HRUD) PATIENTS BESIDE THE INCLUSION CRITERIA FOR UD: 1. No family history of BD in a first or a second degree relative 2. No past history of any sub-threshold hypomania symptoms 3. No history of psychotic symptoms
Exclusion criteria
FOR DEPRESSION AND BIPOLAR SUBJECTS: 1. Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, pervasive developmental disorder. 2. History of receiving electroconvulsive therapy in the past 1 year 3. Use of neuroleptics, mood stabilizers or benzodiazepines in the past 2 weeks. 4. Use of antidepressants in the past 2 weeks. 5. If on fluoxetine in the past, then should not have been on this medication for 5 weeks. 6. Acutely suicidal or homicidal or requiring inpatient treatment. 7. Meeting DSM-IV criteria for other substance/alcohol dependence within the past 6 months or abuse in the past 3 months, excluding caffeine or nicotine. The criteria will be evaluated by interview and urinary toxicology screening. The use of caffeine or nicotine will be recorded. 8. Use of alcohol in the past 1 week before the MRI scan. 9. No serious acute or chronic medical or neurological illness, including previously known HIV positive status (due to possible CNS involvement) as assessed by history, physical examination and laboratory examination including EKG, CBC and blood chemistry. 10. Current pregnancy or breast feeding. 11. Metallic implants or other contraindication to MRI. INCLUSION CRITERIA FOR HEALTHY CONTROLS: Healthy subjects matched for age, gender and ethnicity will be included 1. Ages 15 - 30 years (inclusive) and able to give voluntary informed consent (Parental consent must also be obtained for those under 18 years old) 2. No current or past history of psychiatric illness or substance abuse or dependence. 3. No current or past history of psychiatric illness or substance abuse or dependence in a first degree relative.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HAM-D 17 Item: Hamilton Depression Rating Scale | 24 months | Hamilton depression rating scale (17-item HAM-D): Scores can range from 0 to 52: No depression (0-7); Mild depression (8-16); Moderate depression (17-23); and Severe depression (≥24). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| YMRS: Young Mania Rating Scale | 24 months | Young Mania Rating Scale: Scores can range from 0 to 60: In Remission/No Mania (0-8); Mild (9-12); Moderate (13-18); Severe (19-25); Very Severe (\>25) |
Countries
United States
Participant flow
Pre-assignment details
After enrollment 3 subject were excluded form the study since it was later discovered that they did not meet the criteria.
Participants by arm
| Arm | Count |
|---|---|
| High Risk Depression Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.
Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months. | 51 |
| Low Risk Depression Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant..
Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months. | 56 |
| Healthy Control There is no intervention, but rather phone follow ups conducted as check ins to determine the continued eligibility of the healthy control participant. | 49 |
| Bipolar Bipolar participants are checked in with via phone conversations every three months, and have the opportunity to be scheduled for non-study visits to manage their symptoms. | 33 |
| Total | 189 |
Baseline characteristics
| Characteristic | Low Risk Depression | Healthy Control | High Risk Depression | Bipolar | Total |
|---|---|---|---|---|---|
| Age, Continuous | 25.27 years STANDARD_DEVIATION 3.661 | 24.24 years STANDARD_DEVIATION 3.339 | 22.67 years STANDARD_DEVIATION 3.433 | 23.52 years STANDARD_DEVIATION 3.784 | 23.99 years STANDARD_DEVIATION 3.655 |
| Race/Ethnicity, Customized African American | 6 Participants | 4 Participants | 13 Participants | 7 Participants | 30 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 8 Participants | 1 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Caucasian | 50 Participants | 37 Participants | 37 Participants | 26 Participants | 150 Participants |
| Region of Enrollment United States | 56 participants | 49 participants | 51 participants | 33 participants | 189 participants |
| Sex: Female, Male Female | 38 Participants | 28 Participants | 40 Participants | 22 Participants | 128 Participants |
| Sex: Female, Male Male | 18 Participants | 21 Participants | 11 Participants | 11 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 56 | 0 / 49 | 0 / 33 |
| other Total, other adverse events | 3 / 51 | 4 / 56 | 0 / 49 | 0 / 33 |
| serious Total, serious adverse events | 5 / 51 | 3 / 56 | 0 / 49 | 0 / 33 |
Outcome results
Primary
HAM-D 17 Item: Hamilton Depression Rating Scale
Hamilton depression rating scale (17-item HAM-D): Scores can range from 0 to 52: No depression (0-7); Mild depression (8-16); Moderate depression (17-23); and Severe depression (≥24).
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk Depression | HAM-D 17 Item: Hamilton Depression Rating Scale | 6.6 score on a scale | Standard Deviation 6.62 |
| Low Risk Depression | HAM-D 17 Item: Hamilton Depression Rating Scale | 4.91 score on a scale | Standard Deviation 4.11 |
| Healthy Control | HAM-D 17 Item: Hamilton Depression Rating Scale | 2.333 score on a scale | Standard Deviation 2.732 |
| Bipolar | HAM-D 17 Item: Hamilton Depression Rating Scale | 3.75 score on a scale | Standard Deviation 4.992 |
Secondary
YMRS: Young Mania Rating Scale
Young Mania Rating Scale: Scores can range from 0 to 60: In Remission/No Mania (0-8); Mild (9-12); Moderate (13-18); Severe (19-25); Very Severe (\>25)
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk Depression | YMRS: Young Mania Rating Scale | 0.2 score on a scale | Standard Deviation 0.561 |
| Low Risk Depression | YMRS: Young Mania Rating Scale | 0 score on a scale | Standard Deviation 0 |
| Healthy Control | YMRS: Young Mania Rating Scale | 0 score on a scale | Standard Deviation 0 |
| Bipolar | YMRS: Young Mania Rating Scale | 1.75 score on a scale | Standard Deviation 3.5 |