John P. O’Reardon

Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial

BACKGROUND We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center.

INTRODUCTION Transcranial magnetic stimulation (TMS) is a US Food and Drug Administration-approved treatment for major depressive disorder (MDD) in patients who have not responded to 1 adequate antidepressant trial in the current episode. In a retrospective cohort study, we examined the effectiveness and safety of TMS in the first 100 consecutive patients treated for depression (full DSM-IV criteria for major depressive episode in either major depressive disorder or bipolar disorder) at an academic medical center between July 21, 2008, and March 25, 2011. METHOD TMS was flexibly dosed in a course of up to 30 sessions, adjunctive to current medications, for 85 patients treated for acute depression. The primary outcomes were response and remission rates at treatment end point as measured by the Clinical Global Impressions-Improvement scale (CGI-I) at 6 weeks. Secondary outcomes included change in the Hamilton Depression Rating Scale (HDRS); Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR); Beck Depression Inventory (BDI); Beck Anxiety Inventory (BAI); and the Sheehan Disability Scale (SDS). Enduring benefit was assessed over 6 months in patients receiving maintenance TMS treatment. Data from 12 patients who received TMS as maintenance or continuation treatment after prior electroconvulsive therapy (ECT) or TMS given in a clinical trial setting were also reviewed. RESULTS The clinical cohort was treatment resistant, with a mean of 3.4 failed adequate trials in the current episode. Thirty-one individuals had received prior lifetime ECT, and 60% had a history of psychiatric hospitalization. The CGI-I response rate was 50.6% and the remission rate was 24.7% at 6 weeks. The mean change was -7.8 points in HDRS score, -5.4 in QIDS-SR, -11.4 in BDI, -5.8 in BAI, and -6.9 in SDS. The HDRS response and remission rates were 41.2% and 35.3%, respectively. Forty-two patients (49%) entered 6 months of maintenance TMS treatment. Sixty-two percent (26/42 patients) maintained their responder status at the last assessment during the maintenance treatment. TMS treatment was well tolerated, with a discontinuation rate of 3% in the acute treatment phase. No serious adverse events related to TMS were observed during acute or maintenance treatment. CONCLUSIONS Adjunctive TMS was found to be safe and effective in both acute and maintenance treatment of patients with treatment-resistant depression.

Transcranial magnetic stimulation maintenance as a substitute for maintenance electroconvulsive therapy: a case series.

Background Transcranial magnetic stimulation (TMS) is an efficacious, well-tolerated, noninvasive brain stimulation treatment for major depressive disorder. Electroconvulsive therapy (ECT) is an effective maintenance treatment for depression but is not tolerated by some patients and declined by others. Objective We evaluated the effectiveness of TMS as a substitution strategy for successful maintenance ECT. Methods A consecutive clinical case series (n = 6) of maintenance ECT patients were transitioned to maintenance TMS because of adverse effects from ECT or because of specific patient request and preference. Patients were in either full remission or had clinical response to ECT at the time of transition. Primary outcome was the change in the Beck Depression Inventory (BDI) score from initiation of TMS maintenance sessions to the last observation time point. Relapse of depressive symptoms was also documented. Results Mean age of patients was 64 years, and most were female (n = 5). The majority (5 of 6) were diagnosed with major depressive disorder. Reasons for transition from ECT to TMS were, in order of frequency, cognitive adverse effects, fear of general anesthesia, time burden, lack of remission with ECT, and stigma associated with ECT. The mean frequency of TMS sessions was 1 every 3.5 weeks. Based on BDI scores, all patients maintained or improved their clinical status achieved with ECT at 3 and 6 months of TMS treatment. At last observation (range, 7–23 months), 4 patients maintained or improved their clinical status (total BDI score remained constant or decreased by 1–8 points). Two patients had a relapse after 8 and 9 months. Stimulation was well tolerated with adverse effects limited to headache and scalp discomfort. Conclusions In this case series, TMS was effective and safe when used as a substitution strategy for successful maintenance ECT.

Guidelines for the Management of Depression During Pregnancy

Guidelines regarding the treatment of depression during pregnancy were recently published by the American Psychiatric Association and the American College of Obstetricians and Gynecologists. We provide a commentary on these guidelines.

Vagus Nerve Stimulation (VNS)

Vagus nerve stimulation (VNS) appears to be a safe and reasonably effective treatment modality and represents a new addition to the toolbox of the clinician in treating patients with severe, recurrent unipolar, and bipolar affective disorders. VNS is a bottom-up approach (brain stem to cortex) in treating depression. It modulates the neural circuitry of depression by stimulating vagal afferent fibers in the neck, which carry impulses to the brain stem and target structures involved in mood regulation, including the noradrenergic locus ceruleus and the serotonergic dorsal raphe nucleus.