Duration between two stimulation trains. Chen et al have demonstrated that shorter (<1 second) inter-train intervals increase seizure risk with higher frequencies (such as 20 Hz) and intensities (>100% of motor threshold) of stimulation.9 Based on their studies with healthy volunteers, they recommended several “safe” ranges (such as 5 seconds at 110% of motor threshold). Most trials use 30- to 60-second inter-train intervals.
Most treatments continue 2 to 4 weeks, Monday through Friday, although more frequent treatments are being studied.
EFFICACY FOR DEPRESSION
Most studies of rTMS in depression have compared real rTMS to a sham control or electroconvulsive therapy (ECT).
In earlier studies, the sham procedure typically involved tilting the coil away from the skull. This method has been questioned, however, because of evidence of neuronal depolarization.10
More recent sham coils mimic the real coils’ sound and sensation, without magnetic stimulation.
Despite these methodologic problems and some mixed results, depressed patients receiving rTMS show more favorable results than those receiving sham rTMS.11,12 Several meta-analyses have attempted to quantify rTMS’ efficacy for depression:
- Holtzheimer et al concluded that rTMS was statistically superior to sham rTMS, but the clinical significance of these findings was modest in a population of mostly outpatients with less-severe depression.13
- Burt et al found a statistically strong antidepressant effect, but its magnitude varied and few of the studies yielded a substantial clinical response or remission. The team also noted that rTMS’ long-term efficacy or adverse effects are unknown.14
- Kozel et al concluded that left prefrontal rTMS rendered a significant antidepressant effect with measurable clinical improvement.15
- Gershon et al16 supported an antidepressant effect for rTMS when compared with sham rTMS or ECT.
Ongoing rTMS research includes subjects with many types of mild to severe psychiatric illnesses, including major depression, obsessive-compulsive disorder, and psychosis. Typically, patients referred for experimental approaches have not responded to or tolerated available treatments. Exclusion criteria used by most rTMS studies are listed in the Table.
Table
Medical conditions that preclude use of rTMS
| Serious medical conditions History of seizures Increased intracranial pressure Serious head trauma |
| Myocardial infarction within the past 6 months |
| Pregnancy or childbearing potential (unless reliable contraception is being used) |
| Intracranial metallic implants |
| Pacemakers or other implanted devices |
rTMS vs. ECT. Four randomized, controlled trials have compared rTMS with ECT for treating severely ill, often medication-resistant patients.17-20 Although their methodologies differed, all four studies concluded that rTMS and ECT offer similar efficacy, except that rTMS may be less effective for treating psychotic depression.
One study found ECT more effective than rTMS for psychotic depression, although the patients who received ECT were also treated with antipsychotics and/or antidepressants.17 Our study,19 which did not use these agents, has not corroborated this observation. Preliminary data also indicate comparable relapse rates following acute ECT and rTMS when subjects are followed on maintenance medication.21
ADVERSE EFFECTS
The potential adverse effects of new treatments must always be considered. Thus far, rTMS appears to produce minimal, relatively benign complications, including:
- mild discomfort at the stimulation site
- localized muscle twitching during stimulation
- mild post-treatment headaches—believed caused by muscle contractions—which usually respond to aspirin or acetaminophen
- treatment stimulation-related seizures (rarely).8
The rTMS device makes a loud clicking noise, and subjects wear protective ear plugs during treatment.
Patient experience. The first rTMS session—during which the patient’s motor threshold is determined—can last up to 45 minutes. Subsequent sessions are usually 15 to 20 minutes. Patients are typically apprehensive before the first session but become more relaxed with experience and tolerate the treatments easily.
During the procedure, many patients describe a tapping sensation on the forehead, and some experience slight muscle twitching around the eye or corner of the mouth. As the coil warms, the skin it touches sometimes flushes pink, although this does not seem to bother our patients. They can return to their daily routines immediately after a session.
rTMS for major depression. In our experience, rTMS may help patients with major depression. For example, one patient diagnosed with a major depressive episode with psychotic features was referred to our study comparing rTMS with ECT.19 Her depression had lasted several months, with partial response to ECT treatments. She signed informed consent and was randomly assigned to receive rTMS treatment.
At study admission, the patient’s Hamilton Depression Rating Scale (HDRS) score was 48, indicating moderate to severe depression. Following 10 rTMS sessions, her HDRS score had dropped to 2, with remission of symptoms. No follow-up results were documented.
Cognitive effects. Whereas mood disorders are associated with medication-independent neuropsychological deficits, most studies have found no adverse cognitive effects with rTMS.22 Indeed, some of our rTMS patients have improved in certain cognitive tests, although this may be explained by test-retest effects or better attention and concentration associated with mood improvement.