Clinical trial NCT00045773: Treatment Outcome of Vascular Depression
Official title: Treatment Outcome of Vascular Depression
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Depressive Disorder
Depression
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Duke University
First posted: 2002-09-11
Enrollment: 208
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults 60+ with major depression.

Brief summary: This 12-week study will evaluate the effectiveness of sertraline (Zoloft®) for treatment of depression associated with small vascular lesions in the brain (vascular depression).

Detailed description: Major late life depression (LLD) is an important health problem with a large and growing number of affected individuals. A significant subset of patients with LLD, particularly those with vascular depression, have abnormalities in certain parts of the brain that are evident on MRI scans and may be associated with poor acute and long-term response to antidepressant treatment. Studies have also indicated that LLD patients frequently have frontal lobe dysfunction. A longitudinal study with the antidepressant nortriptyline has demonstrated that frontal lobe dysfunction is associated with poor acute response and a greater risk for recurrence of LLD. However, it is not known if this finding applies to other antidepressants. This study will be the first clinical trial to simultaneously test the effects of specific brain and psychological factors on course of response, remission rate, and other measures of health outcomes in people with LLD.

Participants are treated with sertraline for 12 weeks. During this period, participants undergo cognitive testing, MRI, electrocardiogram (EKG), and laboratory tests. Study visits occur every 2 weeks.

Eligibility criteria: Inclusion Criteria:

1. Ages 60+
2. DSM-IV criteria for MDD
3. Hamilton Depression Rating Scale score \>18
4. No MRI contraindications, e.g. foreign metallic implants, pacemaker
5. Medication free of any psychotropic drug except as otherwise noted for set washout period (see D.2.1)
6. Mini Mental Status Exam score \<21
7. No unstable medical disorders (requiring immediate medical attention)
8. Ability to give informed consent
9. English speaking

Exclusion Criteria:

1. Age \<60
2. Does not meet DSM-IV criteria for MDD
3. Hamilton Depression Rating Scale score \<18
4. MRI contraindications e.g. foreign metallic implants, pacemaker
5. Psychotropic drug use other than zolpidem and lorazepam, prn within 2 weeks of entry
6. Mini Mental Status Exam score \>21, or known primary neurological disorders including Dementia of the Alzheimer type, Parkinson's Disease, multiple sclerosis, seizure disorder.
7. Unstable medical disorders, uncorrected hypothyroidism, or any condition that in the investigators opinion makes the patients unsuitable for a trial
8. Cannot give informed consent
9. Does not speak English

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Washington University Psychiatrist
name: Yvette I. Sheline, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Murali Doraiswamy, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sheline YI, Black KJ, Lin DY, Christensen GE, Gado MH, Brunsden BS, Vannier MW. Stereological MRI volumetry of the frontal lobe. Psychiatry Res. 1996 Oct 7;67(3):203-14. doi: 10.1016/0925-4927(96)02831-4.
citation: Sheline Y, Loenze E, Cross D, et al., (1996) Quantifying white matter lesions in elderly women with depression. Presented at the Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico.
citation: Sheline YI, Freedland KE, Carney RM. How safe are serotonin reuptake inhibitors for depression in patients with coronary heart disease? Am J Med. 1997 Jan;102(1):54-9. doi: 10.1016/s0002-9343(96)00374-9.
citation: Sheline Y.I. Neuroanatomical changes associated with unipolar major depression. The Neuroscientist 4:331-334, 1998
citation: Sheline YI, Price JL, Vaishnavi SN, Mintun MA, Barch DM, Epstein AA, Wilkins CH, Snyder AZ, Couture L, Schechtman K, McKinstry RC. Regional white matter hyperintensity burden in automated segmentation distinguishes late-life depressed subjects from comparison subjects matched for vascular risk factors. Am J Psychiatry. 2008 Apr;165(4):524-32. doi: 10.1176/appi.ajp.2007.07010175. Epub 2008 Feb 15.
citation: Sheline YI, Barch DM, Garcia K, Gersing K, Pieper C, Welsh-Bohmer K, Steffens DC, Doraiswamy PM. Cognitive function in late life depression: relationships to depression severity, cerebrovascular risk factors and processing speed. Biol Psychiatry. 2006 Jul 1;60(1):58-65. doi: 10.1016/j.biopsych.2005.09.019. Epub 2006 Jan 18.
citation: Sheline YI, Pieper CF, Barch DM, Welsh-Bohmer K, McKinstry RC, MacFall JR, D'Angelo G, Garcia KS, Gersing K, Wilkins C, Taylor W, Steffens DC, Krishnan RR, Doraiswamy PM. Support for the vascular depression hypothesis in late-life depression: results of a 2-site, prospective, antidepressant treatment trial. Arch Gen Psychiatry. 2010 Mar;67(3):277-85. doi: 10.1001/archgenpsychiatry.2009.204.