• Mood Disorders

Daily left prefrontal repetitive transcranial magnetic stimulation (TMS) demonstrated therapeutic effects in patients with major depressive disorder (MDD), according to a recent study by George and colleagues. TMS is a brain intervention that alters activity within specific regions of the brain using electrical current. There has been some controversy regarding the reliability of previous sham studies that have investigated TMS, because some feel that sham TMS controls do not adequately mimic active TMS treatment. Thus, the concern was that controls were too obvious to investigators and study participants. The current study was designed with that potential flaw in mind, and the sham control was formatted to closely emulate the somatosensory experience of active treatment, including the sound of the device during administration and the pulsing sensation to the scalp.

This prospective, multicenter, randomized, active sham-controlled (1:1 randomization) trial included 190 patients with unipolar nonpsychotic MDD who were free of antidepressant, antipsychotic, and anticonvulsant medication for at least 2 weeks prior to baseline evaluation. Patients received active repetitive TMS (n=92) to the left prefrontal cortex (10-Hz pulses for 4 seconds with 26-second intervals between pulses for a total of 37.5 minutes per session; total of 3000 pulses per session) using a figure-eight solid-core coil or sham TMS (n=98), which consisted of a similar coil with a metal insert that blocked the magnetic field and scalp electrodes that simulated the active TMS sensation. Treatment was standardized at 120% magnetic field intensity relative to the individual patient's resting motor threshold. Patients received 3 weeks of daily weekday treatment during the fixed-dose phase, followed by 3 additional weeks of blinded treatment for improvers. The two groups were well matched at baseline with regard to demographics and clinical characteristics. Of the 190 intent-to-treat patients, 154 completed and 120 were fully adherent.

The primary outcome was remission rate for the two treatment arms using logistical regression and controlling for age, treatment resistance, study site, and duration of the current depressive episode. Secondary outcomes included response rates, as determined by Hamilton Scale for Depression (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression Severity of Illness Scale (CGI-S), and Inventory of Depressive Symptoms-Self Report (IDS). Investigators also evaluated spontaneous adverse events that were related to repetitive TMS to assess for safety.

Patients who received active TMS treatment demonstrated a significant treatment effect compared with control (OR, 4.2; 95% CI, 1.32 to 13.24; p=0.02). Fourteen percent of patients in the TMS arm remitted versus 5% in the sham arm. The number that was needed to treat was 12. Patients who underwent TMS demonstrated significant improvement in MADRS (p=0.01), CGI-S (p=0.01), and IDS (p=0.001) scores compared with sham control (Table 1).

IIt is important to note that site differences were found during the course of this study. In fact, most remitters (83%) and patients who were found to be less treatment-resistant (66.4%) originated at two of the four study sites. While site and resistance status did not appear to influence primary study results, interpretation of these variables did impact regression estimates.

There was no significant difference in spontaneous adverse events according to treatment arm. Five patients who were receiving TMS withdrew from study participation due to adverse events (one because of syncope after 14 treatments and four because of pain or headaches after initial treatment). No seizures or suicides were documented. The most common adverse events that were reported were headache, discomfort at stimulation site, and insomnia for both groups.

Overall, TMS was associated with more favorable outcomes compared with sham control. Daily left prefrontal TMS therapy was shown to have significantly greater antidepressant effects and was well tolerated in patients with unipolar depression. Safety profiles were similar between the two groups.

• © 2010 MD Conference Express