The purpose of this study is to determinate if accelerated rTMS treatment over 1.5 days is effective for ameliorating depression in Parkinson's disease.

Objective: The goal of this study is to investigate a new approach to administering repetitive transcranial magnetic stimulation (rTMS) in patients with refractory depression. (Please Note: The original requirement for comorbid Parkinson's disease has been dropped from this study).

Research Plan: This inpatient study will provide an initial test for the hypothesis that accelerated rTMS is an effective treatment for depression. Followup testing will help delineate the time course of response.

Methods: The rTMS treatment site over left dorsolateral prefrontal cortex will be 5.5cm anterior to the hand motor area. Treatments consisting of 1000 total pulses at 10 Hz and 100% motor threshold will be administered hourly for 1.5 days, totaling 15 sessions. A comprehensive test battery will be administered just before and after treatment, at 3 weeks, and at 6 weeks after treatment.

Clinical Relevance: We expect that accelerated rTMS treatments will lessen the degree of depression to the same extent as rTMS treatments of longer duration, but far more rapidly. A much shorter hospitalization would be more easily tolerated. In addition, reducing the duration of hospitalization substantially reduces burdens and costs to hospital, staff, and caregivers, while more rapidly enhancing function and quality of life.

Inclusion Criteria:

• Age 18-80 years.
• Patients who meet DSM-IV criteria for Major Depressive Episode, severe, treatment resistant, with or without psychotic features.
• Consent to treatment with rTMS.

Exclusion Criteria:

• Patients with Delirium or Substance Dependence within the last 6 months. Patients will be screened initially with the Michigan Alcohol Screening Test (MAST) and Mini-Mental Status Examination and further evaluated if clinically indicated.
• Patients with other significant central neurological disorders including increased intracranial pressure, brain mass, epileptic seizures, stroke, transient ischemic attack within two years, cerebral aneurysm, dementia, multiple sclerosis or other major CNS dysfunction.
• Pregnant women.
• Patients with cardiac pacemakers, other intracardiac lines, cochlear implants, aneurism clips, or other intracranial implants with the exception of dental fillings.
• Patients with significant heart disease or with acute, unstable medical conditions that require stabilization (e.g., uncontrolled hypertension, bleeding) prior to treatment.
• Patients who require continued treatment with antipsychotics including clozapine and risperidone, benzodiazepines, lithium or anticonvulsants. Patients will be allowed to continue on a stable dose of antidepressants and use zolpidem, since the latter is not felt to affect seizure threshold.
• Patients who are unable to ambulate independently and complete the assessment protocol.