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Objective: Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression. Methods: Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6–8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods. Results: Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment. Conclusions: Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

Objective: To examine changes in motor cortical excitability in adolescent subjects receiving 30 sessions of high-frequency prefrontal repetitive transcranial magnetic stimulation (rTMS). Methods: Eight adolescents with treatment-resistant major depressive disorder (MDD) enrolled in an open augmentation trial of 10 Hz rTMS. Resting motor thresholds were obtained by the visualization of movement method with a maximum likelihood threshold hunting computer algorithm at baseline and after every five sessions of rTMS. Motor threshold was recorded as the percentage of total machine output at each measurement. Results: Motor threshold data from baseline, weeks 2, 4, and 5 were included in a mixed model repeated measure analysis to examine a change in least square mean effect over time. The omnibus effect did not reach statistical significance (F=1.25, p=0.32). However, multiple comparisons from the overall model demonstrated a decrease in the least square mean motor threshold. The mean contrast from baseline to week 5 approached significance (p=0.07). Moreover, a post-hoc analysis with a Wilcoxon signed ranks test demonstrated a significant decrease at week 5 (p=0.03). Conclusions: This suggests that high-frequency rTMS may increase cortical excitability in adolescents with treatment-resistant MDD.

Electroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements. To compare the efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT. This multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold. All three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43-66%) with right unilateral, 61% with bifrontal (95% CI 50-71%) and 64% (95% CI 53-75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments. Each electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.

Depression is a common disorder that is becoming better understood as an illness that can be chronic, recurrent, and refractory to treatment. Depression can produce substantial suffering and profoundly affect a patient's self-esteem, relationships, and functional capacity. The improved adverse-effect profile and safety from overdose of selective serotonin reuptake inhibitors (SSRIs) have led to treatment of milder forms of depression and thus increased treatment of depression overall. This article synthesizes several previously published reviews and psychopharmacology resources and addresses practical issues related to initiating, monitoring, continuing, and discontinuing SSRIs. Precautions related to SSRI use and important considerations for various types of depression are discussed.

Severe mental illnesses often remain chronic and refractory to medication, leading to substantial morbidity and mortality. For more than 60 years, electroconvulsive therapy has been the only nonpharmacological psychiatric procedure available to treat severe or medication-refractory major depressive disorder and other psychiatric conditions. Memory dysfunction remains the most serious adverse effect, and current research focuses on attempts to ameliorate this complication. Transcranial magnetic stimulation and vagus nerve stimulation, 2 new neuropsychiatric technologies, are emerging as possible additions to our therapeutic armamentarium. Besides providing therapeutic benefits, these 3 methods may help elucidate the pathophysiology of psychiatric illness.

Major depression is a common medical illness, which is projected to be second only to ischemic heart disease for global disease burden by 2020. Depression is often a recurrent illness and can be difficult to treat. Because an estimated 20% to 40% of patients fail to respond to antidepressant medications and psychotherapy, new treatment options for depression are needed. ABOUT THE AUTHORS Shirlene M. Sampson, MD, MSc, is with the Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN. H. Brent Solvason, MD, PhD, is with the Department of Psychiatry, Stanford University, Palo Alto, CA. Mustafa Husain, MD, is with the Department of Psychiatry, University of Texas Southwestern, Dallas, TX. Address correspondence to: Shirlene M. Sampson, MD, MSc, Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905; fax 507-284-4158; or email sampson.shirlene@mayo.edu . Dr. Sampson is a research grant recipient for Neuronetics Inc. , developer of NeuroStar TMS (transcranial magnetic stimulation) System. Drs. Solvason and Husain disclosed no relevant financial relationships. EDUCATIONAL OBJECTIVES Discuss technical considerations in performing transcranial magnetic stimulation (TMS). Discuss safety issues related to the use of TMS. Assess how to approach screening patients for possible TMS treatment for depression.

BackgroundElectroconvulsive therapy (ECT) is an effective treatment for majordepression. Optimising efficacy and minimising cognitive impairment aregoals of ongoing technical refinements.AimsTo compare the efficacy and cognitive effects of a novel electrodeplacement, bifrontal, with two standard electrode placements, bitemporaland right unilateral in ECT.MethodThis multicentre randomised, double-blind, controlled trial (NCT00069407)was carried out from 2001 to 2006. A total of 230 individuals with majordepression, bipolar and unipolar, were randomly assigned to one of threeelectrode placements during a course of ECT: bifrontal at one and a halftimes seizure threshold, bitemporal at one and a half times seizurethreshold and right unilateral at six times seizure threshold.ResultsAll three electrode placements resulted in both clinically andstatistically significant antidepressant outcomes. Remission rates were55% (95% CI 43–66%) with right unilateral, 61% with bifrontal (95% CI50–71%) and 64% (95% CI 53–75%) with bitemporal. Bitemporal resulted in amore rapid decline in symptom ratings over the early course of treatment.Cognitive data revealed few differences between the electrode placementson a variety of neuropsychological instruments.ConclusionsEach electrode placement is a very effective antidepressant treatmentwhen given with appropriate electrical dosing. Bitemporal leads to morerapid symptom reduction and should be considered the preferred placementfor urgent clinical situations. The cognitive profile of bifrontal is notsubstantially different from that of bitemporal.