Effectiveness of Nimodipine Plus Antidepressant Medication in Treating Vascular Depression

Phase 4

Terminated

Conditions: Depression

Interventions: Drug: Nimodipine
Drug: Placebo

Registration Number: NCT00781326

Lead Sponsor: University of Pittsburgh

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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 9

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open Label Antidepressant	Placebo	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.
Open Label Antidepressant	Nimodipine	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.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures