Patients with a major depressive episode responding to treatment with repetitive transcranial magnetic stimulation (rTMS) are resistant to the effects of rapid tryptophan depletion.

Repetitive transcranial magnetic stimulation (rTMS) appears to be efficacious in the treatment of major depression based on the results of controlled studies, but little is known about its antidepressant mechanism of action. Mood sensitivity following rapid tryptophan depletion (RTD) has been demonstrated in depressed patients responding to SSRI antidepressants and phototherapy, but not in responders to electroconvulsive therapy (ECT). We sought to study the effects of RTD in patients with major depression responding to a course of treatment with rTMS. Twelve subjects treated successfully with rTMS monotherapy underwent both RTD and sham depletion in a double-blind crossover design. Depressive symptoms were assessed using both a modified Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The differential change in depression scores across the procedures was compared. No significant difference in mood symptoms was noted between RTD and the sham-depletion procedure on either continuous measures of depression, or in the proportions of subjects that met predefined criteria for a significant degree of mood worsening. Responders to rTMS are resistant to the mood perturbing effects of RTD. This suggests that rTMS does not depend on the central availability of serotonin to exert antidepressant effects in major depression.

Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond.

Neuromodulation appears to be emerging gradually as a new therapeutic field in psychiatric treatment. It encompasses neuropsychiatric medical devices, such as vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and electroconvulsive therapy (ECT). As a therapeutic approach to affective disorders, neuromodulation shifts the focus from the monoamine synapse to neural circuitry of the brain, which is dysregulated in depression. This neural circuitry has been elaborated on over the course of 15 years of neuroimaging research in mood disorders and is now believed to encompass disturbances in a frontolimbic network. These include reduced metabolism and blood flow in the prefrontal cortex and anterior cingulate and pathologically increased activity in the subgenual cingulate and amygdala.VNS is an implanted device that has established efficacy in pharmaco-resistant epilepsy. It was approved by the FDA for the treatment of severe, recurrent unipolar and bipolar depression in July of 2005. VNS adopts a bottom-up approach to modulating the neural circuitry of depression by stimulating vagal afferent fibers in the neck, which carry impulses to the brain stem to target there the locus ceruleus and dorsal raphe nucleus. Now that VNS has moved beyond the experimental phase and into the clinic, psychiatrists are faced with deciding who is an appropriate patient for this surgical implant and how to integrate VNS into existing treatment in order to optimize both efficacy and safety.This review of VNS will assess the efficacy and safety data that led to the FDA approval. We will also review for the busy clinician how VNS is likely to translate into clinical practice as a treatment option for patients in need who are suffering from severe depression.

Long-term maintenance therapy for major depressive disorder with rTMS.

OBJECTIVE: There is growing evidence to support the short-term antidepressant effects of repetitive transcranial magnetic stimulation (rTMS), but few published data pertain to the maintenance treatment of patients with DSM-IV-diagnosed major depressive disorder who have responded acutely to rTMS. We describe long-term maintenance therapy for major depressive disorder with rTMS. METHOD: Repetitive transcranial magnetic stimulation was applied in 10 adults over the left prefrontal cortex at 100% of motor threshold, most often at a frequency of 10 Hz for sessions consisting of 40 trains at 5 seconds per train (2000 pulses per session), for periods ranging from 6 months to 6 years. Session frequency averaged 1 to 2 per week. The study was conducted in the TMS lab of an academic medical center. RESULTS: Seven of the 10 subjects experienced either marked or moderate benefit, which was sustained without the addition of concomitant antidepressant medication in 3 cases. There were no serious adverse events reported by any participant. The seizure rate for the 1831 reported rTMS sessions was zero. CONCLUSIONS: These data, while open label, suggest that maintenance rTMS may be a safe and effective treatment modality in some patients with unipolar depression. Further research into the long-term safety and efficacy of rTMS is warranted.