The major aim of this study is to carry out a sequential Phase I trial of prefrontal transcranial magnetic brain stimulation (TMS) and electroconvulsive therapy (ECT) in patients with Parkinson's disease (PD) and severe depression. Depression complicates PD in up to 50% of cases, leading to further deterioration of motor performance and quality of life; but antidepressant medication fails or produces intolerable side effects in 25-30% of patients. Case reports and uncontrolled trials suggest that ECT is effective in ameliorating simultaneously the mood and motor symptoms of PD. Only a few small studies of ECT in PD have been prospective or randomized, the assessment protocols have been limited, and the results have been variable. TMS is a new, promising, alternative treatment for refractory depression, which appears to be easier and safer than ECT. Requiring no hospitalization, anesthesia, or recovery time, TMS is now being investigated as an alternative therapy for mood disorders. TMS has not been studied in depressed patients with PD or in other serious central nervous system diseases.

This study extends our past and present research in PD, depression, ECT, and TMS. We will comprehensively evaluate the effects of left prefrontal TMS on mood, motor, and neuropsychological function, together with quality of life indices in depressed PD patients. All patients will initially receive treatment with TMS. Those who fail to benefit will proceed to ECT. Comprehensive evaluation will be continued for another eight weeks in both the TMS-only and ECT groups. The key issues addressed by these studies include: (1) the potential benefit of TMS on mood and movement in depressed PD patients, and (2) the tightness of the association between mood and motor function after TMS and ECT. Overall, these studies will provide important preliminary data on the relationships among mood, cognitive and motor function in PD, and their influence on quality of life. The results will help in directing future applications of TMS as an alternative therapy for brain disorders, and will further elucidate the relative benefits of both TMS and ECT in depressed PD patients. A positive effect from TMS should be an impetus towards randomized, placebo-controlled trials.

Inclusion Criteria:

• Have a diagnosis of idiopathic Parkinson's Disease and meet DSM-IV criteria for Major Depressive Episode, severe, with or without psychotic features, or for Mood Disorder secondary to PD with major depression-like episode.
• Have demonstrated an inadequate clinical response to at least one antidepressant medication in adequate dosage for at least six weeks, or an adverse event requiring discontinuation.