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.
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