The purpose of this study is to determine whether repetitive transcranial magnetic
stimulation is effective in the treatment of major depression that is refractory to medical
Despite the utility of modern psychotropic medications, depression remains a medical problem
with major societal impact. Electroconvulsive therapy (ECT) is an effective somatic
treatment for depression. However, ECT has disadvantages, including risks attendant with
general anesthesia and significant cognitive side effects (e.g. confusion and memory loss).
An effective but safer somatic therapy for depression could help many patients.
The brain can be stimulated non-invasively by using time-varying magnetic fields to induce
electrical currents within the cerebral cortex, a technique known as transcranial magnetic
stimulation. Preliminary investigations have provided promising evidence of improved mood
associated with high frequency repetitive transcranial magnetic stimulation (rTMS) of left
prefrontal cortex in patients with medication-resistant major depression. However, the role
of stimulus laterality in the effects of prefrontal rTMS have not been tested
systematically. Furthermore, previous studies have likely been confounded by inadequate
patient blinding and by a lack of standardization of psychotropic medication treatment.
Therefore, we propose to use a carefully controlled clinical trial to directly test the
hypothesis that the effects of prefrontal rTMS on mood are related to the laterality of
magnetic stimulation. We also intend to improve blinding in comparison to previous studies
by: 1) employing a parallel-group study design comparing real and simulated rTMS, as opposed
to a crossover study design; 2) using specially constructed sham magnetic coils which can be
placed directly on the scalp surface, to more effectively simulate rTMS; and 3) using trains
of weak electrical impulses to simulate the cutaneous scalp stimulation associated with
rTMS. We will minimize confounding effects of medications and antidepressant withdrawal by:
1) requiring all patients fail a monitored clinical selective serotonin reuptake inhibitor
(SSRI) trial prior to rTMS; and 2) continuing SSRI treatment during the rTMS phase of the
trial. Demonstration of therapeutic efficacy of rTMS in this rigorously controlled clinical
trial would provide a foundation for further investigation and development of this novel
potential treatment modality.
- Meets DSM-IV criteria for major depressive episode without psychotic features
- Has a total score of 18 or higher on the Hamilton Rating Scale for Depression
- Has failed to respond to at least two separate trials of treatment for at least 4
weeks with therapeutic dosages of antidepressant medication (including at least one
SSRI) or has been intolerant of at least three different antidepressant medications
(including at least one SSRI).
- Taking medications that may lower seizure threshold
- History of neurological illness, epilepsy or seizure disorder, intracranial tumor, or
major head trauma leading to loss of consciousness of any duration.
- Evidence of central nervous system disease based on baseline complete neurological
examination, EEG and contrast-enhanced computerized tomography or magnetic resonance
imaging of the brain
- History of implanted pacemaker or medication pump, metal plate in skull, or metal
objects in the eye or skull.
- Axis II diagnosis of cluster A (paranoid, schizoid, or schizotypal) or cluster B
(antisocial, borderline, histrionic, or narcissistic) personality disorder
- Axis II diagnosis of mental retardation
- History of schizophrenia, schizoaffective disorder, other functional psychosis,
rapid-cycling bipolar illness, or alcohol or drug abuse within the past year.
- Need for rapid clinical response due to conditions such as inanition, psychosis, or
- A medical condition that is not well controlled, such as diabetes or hypertension, or
concomitant medical or nutritional problems necessitating hospitalization
- Patients taking anticonvulsant mood stabilizers (e.g., carbamazepine, valproic acid).
- Patients otherwise unable to grant informed consent.
- Patients who are pregnant.