Depression
Conditions
Keywords
Depressive Disorder, Major, Cerebrovascular Disorders, Risk Factors, Nimodipine
Brief summary
This study will examine whether combined use of an antidepressant medication and the medication nimodipine reduces risk of depression relapse in patients with vascular depression.
Detailed description
Depressed elderly patients often show signs of cerebrovascular disease, commonly known as a stroke. Some scientists theorize that having cerebrovascular disease may affect depression in older adults in one of three ways: by causing depression, by making it more likely that people who have been depressed have a relapse, or by maintaining certain depressive symptoms in those already depressed. The combination of depression and cerebrovascular disease in older adults is referred to as vascular depression and is associated with psychomotor slowing, functional impairment, and cognitive impairment. Additionally, the likelihood of improvement or remission is lower in vascular depression and is more difficult to treat over time. Nimodipine (NIM) is FDA approved to reduce incidence and severity of problems with blood flow resulting from a particular type of stroke. In addition to improving blood flow in the brain following a stroke, NIM also protects neurons from injury or degeneration and has cognitive and functional benefits. These positive effects of NIM may make it useful for treatment of vascular depression. In a previous study of people with vascular depression, pairing NIM with the antidepressant fluoxetine showed greater improvements in depression treatment outcomes, higher likelihood of full remission, and less incidence of depression recurrence than using fluoxetine alone. This study will examine whether pairing NIM with other antidepressants will reduce recurrence of vascular depression. Participation in this study will last 56 weeks and will be divided into two phases. In the first phase, participants will receive antidepressant medication without NIM. Participants will begin taking escitalopram but may be switched to duloxetine or have lorazepam added to their regimen, depending on individual treatment effectiveness and side effects. The first phase will last between 6 and 24 weeks, ending when the individual participant either responds to medication or experiences 24 weeks of nonresponse. During the first phase, participants will attend weekly study visits, during which researchers will assess medication effectiveness and monitor side effects. At the beginning of the second phase, participants will be randomly assigned to receive either NIM or a placebo in addition to continuing with the antidepressant medication already helping them. Participants will take NIM or the placebo for 8 months, undergoing weekly study visits for the first month and monthly study visits for the last 7 months. During these visits, researchers will monitor the participants' health and reactions to their medications. After 4, 16, and 32 weeks, an EKG test will be performed, and after 16 and 32 weeks, cognitive and physical tests will be performed again. After the 8 months, participants will attend three weekly study visits while their use of medication is lowered and then ended. For information on a related study, please follow this link: http://clinicaltrials.gov/show/NCT00177424
Interventions
DRUGNimodipine
Nimodipine will be initiated at one, 30-mg tablet three times a day for 1 week, increased to 2 tablets three times a day for 1 week, and then increased to three tablets three times a day for the remaining 30 weeks of the study. Participants who cannot tolerate the maximum dose of 270 mg/day will be maintained at the highest tolerable dose.
DRUGPlacebo
Placebo will be given in doses matching those of nimodipine.
Sponsors
National Institute of Mental Health (NIMH)
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Current DSM-IV (Diagnostic and Statistical Manual) diagnosis of major depression * Score greater than 15 on the 24-item Hamilton Depression Rating Scale (HDRS24) * Significant cerebrovascular disease risk factors, as defined by the presence of more than three of the following: 1. Arterial hypertension, defined by a systolic blood pressure higher than 140 mm Hg or a diastolic blood pressure higher than 90 mm Hg, or by both a self-reported hypertension diagnosis and use of antihypertensive medication 2. Diabetes mellitus, defined by a fasting blood glucose level higher than 126 mg/dl or treatment with hypoglycemic agents or insulin in the year before study entry 3. Obesity, defined by a current body mass index (BMI) greater than 30 4. Hyperlipidemia, defined by either a confirmed prior diagnosis or a current fasting cholesterol level higher than 200 mg/dl 5. Current smoker * Able to swallow oral medication * Identification of a family member or friend willing and able to participate as a source of corroborating information * Able to speak English * A hearing capacity adequate to respond to a raised conversational voice
Exclusion criteria
* Current diagnosis of major depression with psychosis, schizophrenia, bipolar disorder, schizophreniform disorder, schizoaffective disorder, schizotypal disorder, or obsessive compulsive disorder * Meets DSM-IV criteria for dementia or has a score of 17 or lower on the Mini Mental State Examination * Met DSM-IV criteria for drug or alcohol dependence within the past 6 months * Not responsive to therapeutic trials of either escitalopram or duloxetine for the current major depressive episode * Acute, severe, or unstable medical disorder likely to interfere with treatment, such as untreated thyroid disorder * History of epilepsy * Clinically reported stroke within the past year * First-degree heart block, determined after correcting for age * Symptomatic hypotension or symptomatic orthostatic hypotension * History of nontolerance or allergy to both escitalopram and duloxetine therapy, including history of selective serotonin reuptake inhibitor (SSRI)-related syndrome of inappropriate anti-diuretic hormone secretion (SIADH) * Significant allergy to NIM or other ingredients contained in the study medication * Taken monoamine oxidase inhibitors (MAOIs) within the 2 weeks prior to the first administration of double-blind study medication * Requires treatment with amiodarone, protease inhibitors, dalfopristin or quinupristin, valproic acid, triazole antifungal agents (e.g., itraconazole), reserpine, methyldopa, guanethidine, or clonidine during the course of the study * May require drugs known to interact with NIM during the course of the study * Refusal to allow the research team to contact participant's primary medical provider * Planning to become pregnant during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (24 Item) [Phase I Primary Outcome] | End of Phase I (at 24 weeks) | Hamilton Depression Rating Scale (24 item) measures symptoms of major depression. We report total score which is the sum of all items. Total score range is 0 to 76 with higher scores indicating more severe depression. We reports scores at end of Phase I for subjects completing the phase. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Antidepressant In Phase 1, all participants will be placed on antidepressant medication. In Phase 2, participants will continue with their antidepressant medication and also receive receive either nimodipine or placebo. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase I | Adverse Event | 1 |
| Phase I | Physician Decision | 2 |
| Phase I | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Open Label Antidepressant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 66.2 years STANDARD_DEVIATION 8.7 |
| Cumulative Illness Rating Scale (Geriatric) total | 8.3 units on a scale STANDARD_DEVIATION 2 |
| Hamilton Depression Rating Scale (24 item) | 20.5 units on a scale STANDARD_DEVIATION 2.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Hamilton Depression Rating Scale (24 Item) [Phase I Primary Outcome]
Hamilton Depression Rating Scale (24 item) measures symptoms of major depression. We report total score which is the sum of all items. Total score range is 0 to 76 with higher scores indicating more severe depression. We reports scores at end of Phase I for subjects completing the phase.
Time frame: End of Phase I (at 24 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Antidepressant | Hamilton Depression Rating Scale (24 Item) [Phase I Primary Outcome] | 9.5 units on a scale | Standard Deviation 0.7 |