Vascular depression in the elderly has been shown to be more refractory to treatment and to have a poorer outcome than non-vascular depression. This study will examine the effectiveness of rapid-transcranial magnetic stimulation over 3 weeks followed by therapeutic blood levels of nortriptyline in the treatment of vascular depression and maintenance of remission over 12 weeks. Patients who have failed at least one treatment for vascular depression will be randomized using double blind controls to treatment with rapid transcranial magnetic stimulation (rTMS) followed by nortriptyline or sham rTMS followed by nortriptyline. We have developed techniques for the uniform administration of rTMS in anatomical location and spatial alignment of the stim coil. We predict that patients given rTMS will have a higher response rate to treatment than placebo rIMS and that over the 9 weeks of nortriptyline they will maintain a lower Ham-D score than the patients given nortriptyline alone. Prior to beginning nortriptyline treatment patients will be genotyped using P450 oligonucleotide microassays for substitutions that affect the CYP2D6 enzyme, which metabolizes nortriptyline. We predict that the patient with null alleles will metabolize nortriptyline so slowly that their side effects ratings will be very high and they will drop out of the study. Patients with alleles encoding extensive or rapid metabolism will relapse because they will be unable to maintain a steady nortriptyline level. Outcome measures will involve response rate to each treatment, relapse rates for each treatment, the size, number, or location of the vascular lesion or the amount of regional brain atrophy or other demographic or prior historical data. We will also examine outcome related to treatment as measured by improvement in activities of daily living, quality of life and cognitive function. We predict that patients given rIMS will improve their cognitive function more than sham treated patients and that the amount of frontal brain atrophy will correlate with both response of depression (i.e. more atrophy lower response rate) and cognitive function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH063405-02
Application #
6528945
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Rudorfer, Matthew V
Project Start
2001-09-18
Project End
2006-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
2
Fiscal Year
2002
Total Cost
$438,969
Indirect Cost
Name
University of Iowa
Department
Psychiatry
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Capizzano, Aristides A; Jorge, Ricardo E; Robinson, Robert G (2010) Limbic metabolic abnormalities in remote traumatic brain injury and correlation with psychiatric morbidity and social functioning. J Neuropsychiatry Clin Neurosci 22:370-7
Narushima, Kenji; McCormick, Laurie M; Yamada, Thoru et al. (2010) Subgenual cingulate theta activity predicts treatment response of repetitive transcranial magnetic stimulation in participants with vascular depression. J Neuropsychiatry Clin Neurosci 22:75-84
Robinson, Robert G; Tenev, Veselin; Jorge, Ricardo E (2009) Citalopram for continuation therapy after repetitive transcranial magnetic stimulation in vascular depression. Am J Geriatr Psychiatry 17:682-7
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Narushima, K; Kosier, J T; Robinson, R G (2003) A reappraisal of poststroke depression, intra- and inter-hemispheric lesion location using meta-analysis. J Neuropsychiatry Clin Neurosci 15:422-30

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