Only 28% to 33% of patients with major depression experience remission after their first antidepressant treatment, according to results of the Sequenced Treatment Alternative to Relieve Depression (STAR*D) trial.1 Therapeutic options include switching to an alternate antidepressant, augmentation with a second antidepressant, psychotherapy, mood stabilizers, or second-generation antipsychotics.
In October 2008, the FDA approved a new option: transcranial magnetic stimulation (NeuroStar TMS Therapy), a neuro-modulation approach indicated for patients with major depressive disorder (MDD) who failed 1 adequate antidepressant trial in the current episode (Table 1).
Table 1
Transcranial magnetic stimulation: Fast facts
| Brand name: NeuroStar TMS Therapy |
| Class: Class II medical device |
| Indication: Treatment of major depressive disorder in adults who failed to achieve satisfactory improvement from 1 prior antidepressant medication at or above the minimal effective dose and duration in the current depressive episode |
| Approval date: October 7, 2008 |
| Availability: Limited number of treatment centers; see www.NeuroStarTMS.com |
| Manufacturer: Neuronetics, Inc. |
| Recommended dose: 75 10-Hz, 4-second trains; 26-second intertrain interval; administered over the left dorsolateral prefrontal cortex; 5 days a week, up to 6 weeks |
How it works
TMS delivers intense intermittent magnetic pulses produced by an electrical charge into a ferromagnetic coil. The intensity of the pulse is similar to that of MRI (1.5 to 2 tesla); however, in MRI the magnetic field is constantly on, whereas in TMS the field is exceptionally brief (milliseconds).
For depression treatment, the coil is usually placed on the scalp over the left dorsolateral prefrontal cortex (DLPFC). Pulses are delivered in a rapid, repetitive train, causing neuronal depolarization in a small area of the cerebral cortex and distal effects in other neurocircuits.
For depression, standard outpatient treatment consists of 5 daily sessions per week for up to 6 weeks. Each session takes approximately 40 minutes, and patients typically return to normal daily activities without difficulty. Initially, NeuroStar TMS will be available in a limited number of treatment centers (see Related Resource).
Intensity of treatment is individualized by adjusting parameters that affect delivery of the magnetic pulses. Motor threshold (MT) is the level of stimulation required to produce movement in a contralateral target muscle, such as the abductor pollicis brevis that causes contraction of the thumb. Once this level is determined, pulses are administered at an intensity relative to the MT (such as 120%). Single TMS pulses are used to find the relevant area of the motor cortex, whereas repetitive pulses are applied over the left DLPFC for therapy.
Frequency of stimulation is measured in cycles per second or hertz (Hz). Stimulation train is the duration during which pulses are administered, and the intertrain interval (ITI) is the time between stimulation trains. Other parameters include site of stimulation and number of treatments per day, week, and course. Recommended treatment levels appear in (Table 2).
Table 2
TMS depression treatment parameters
| Parameter | Definition | Recommended treatment level | |
|---|---|---|---|
| Motor threshold | Level of stimulation required to produce contractions in the contralateral target muscle (abductor pollicis brevis, which causes contraction of the thumb) | 120% | |
| Frequency of stimulation | Measured in cycles per second or hertz (Hz) | 10 Hz | |
| Stimulation train | Duration of the stimulation | 4 seconds | |
| Intertrain interval | Time between stimulation trains | 26 seconds | |
| Site of stimulation | Where in the brain the stimulation will occur | Left dorsolateral prefrontal cortex | |
| Number of treatments | How many times the patient receives stimulation/treatment | 5 days per week for up to 6 weeks | |
| Total stimulation time | Number of stimulations given in a session | 3,000 stimulations per session | |
| TMS: transcranial magnetic stimulation | |||
Efficacy
George et al2 first reported TMS for depression in 1995. Initial small, open-label studies examined a variety of treatment intensities, durations, and stimulation sites. Several sham-controlled studies further refined treatment parameters. These studies generally found TMS efficacious, but questioned the robustness of the clinical effect.
To better assess the antidepressant effect of TMS, studies employed larger samples and more aggressive treatment parameters. Avery et al3 randomized 68 patients to 15 sessions of active or sham TMS over the left DLPFC. Each treatment consisted of 32 10-Hz, 5-second trains at 110% MT with a 25-second ITI. At 1 and 2 weeks after treatment, 31% of subjects in the active treatment group showed a significant decrease in symptoms—defined as ≥50% reduction in Hamilton Depression Rating Scale (HDRS) score—versus 6% in the sham group. In addition, 20% of subjects in the active TMS group achieved remission (defined as HDRS score
The largest trial of TMS monotherapy (N=301) for moderately treatment-resistant major depression was completed in 2007.4 This 3-phase study began with a 4- to 6-week, randomized, double-blind activeversus-sham TMS procedure, followed by 6 weeks of open-label TMS in initial nonresponders. The third phase reintroduced TMS over 6 months as needed to augment maintenance antidepressant medication.