E. Baron Short

The expanding evidence base for rTMS treatment of depression.

Purpose of review Daily left prefrontal transcranial magnetic stimulation (TMS) for several weeks was first proposed as an acute treatment for depression in the early 1990s, and was Food and Drug Administration (FDA) approved in 2008. In the past year, several important studies have been published that extend our understanding of this novel treatment approach. Recent findings The first round of multisite clinical trials with TMS addressed whether prefrontal rTMS has efficacy and were conducted in carefully selected depressed patients who were antidepressant medication free. Several more recent studies assess the clinical effectiveness of TMS and report that about 35–40% of real-world patients who are commonly taking adjunctive antidepressants reach remission with a modest side effect profile. There are also new studies examining the durability of the TMS-induced antidepressant effect. Fifty-eight percent of TMS remitters remain remitted at 3-month follow-up. Summary These recent studies suggest that daily left prefrontal TMS over several weeks as a treatment for depression not only appears to have efficacy in rigorous randomized controlled trials, but is effective in real-world settings, with remission in 30–40% of patients. The TMS antidepressant effect, once achieved, appears to be as durable as with other antidepressant medications or interventions. Much more research is needed, particularly with issues such as the TMS coil location, stimulation intensity and frequency, and dosing strategy.

Regional Brain Activation during Meditation Shows Time and Practice Effects: An Exploratory FMRI Study

Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions of 12 min and performed four sessions of a 6 min control task. Individual and group t-maps were generated of overall meditation response versus control response and late meditation response versus early meditation response for each subject and time courses were plotted. For the overall group (n = 13), and using an overall brain analysis, there were no statistically significant regional activations of interest using conservative thresholds. A region of interest analysis of the entire group time courses of DLPFC and ACC were statistically more active throughout meditation in comparison to the control task. Moreover, dividing the cohort into short (n = 8) and long-term (n = 5) practitioners (>10 years) revealed that the time courses of long-term practitioners had significantly more consistent and sustained activation in the DLPFC and the ACC during meditation versus control in comparison to short-term practitioners. The regional brain activations in the more practised subjects may correlate with better sustained attention and attentional error monitoring. In summary, brain regions associated with attention vary over the time of a meditation session and may differ between long- and short-term meditation practitioners.

Efficacy of Transcranial Direct Current Stimulation and Repetitive Transcranial Magnetic Stimulation for Treating Fibromyalgia Syndrome: A Systematic Review

Objective:  To systematically review the literature to date applying repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) for patients with fibromyalgia syndrome (FMS).

Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: A randomized, controlled pilot study

Summary Ten sessions of adjunctive transcranial magnetic stimulation to the left prefrontal cortex may significantly reduce fibromyalgia pain compared to baseline pain. ABSTRACT Transcranial magnetic stimulation (TMS) of the prefrontal cortex can cause changes in acute pain perception. Several weeks of daily left prefrontal TMS has been shown to treat depression. We recruited 20 patients with fibromyalgia, defined by American College of Rheumatology criteria, and randomized them to receive 4000 pulses at 10 Hz TMS (n = 10), or sham TMS (n = 10) treatment for 10 sessions over 2 weeks along with their standard medications, which were fixed and stable for at least 4 weeks before starting sessions. Subjects recorded daily pain, mood, and activity. Blinded raters assessed pain, mood, functional status, and tender points weekly with the Brief Pain Inventory, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire. No statistically significant differences between groups were observed. Patients who received active TMS had a mean 29% (statistically significant) reduction in pain symptoms in comparison to their baseline pain. Sham TMS participants had a 4% nonsignificant change in daily pain from their baseline pain. At 2 weeks after treatment, there was a significant improvement in depression symptoms in the active group compared to baseline. Pain reduction preceded antidepressant effects. TMS was well tolerated, with few side effects. Further studies that address study limitations are needed to determine whether daily prefrontal TMS may be an effective, durable, and clinically useful treatment for fibromyalgia symptoms.

Brain stimulation for the treatment of psychiatric disorders

Purpose of review There has been a resurgence of interest in brain stimulation techniques as therapies for psychiatric disorders. Various names are used for this class of treatments: neuromodulation, somatic therapies, brain stimulation techniques. The methods in this class range from non-invasive (transcranial magnetic stimulation) to invasive brain surgery (deep brain stimulation). Recent findings Within the past year, the results of several large multicenter trials have been published, clearing the way for US Food and Drug Administration approval of vagus nerve stimulation for recurrent treatment-resistant depression and a pending consideration of approving transcranial magnetic stimulation for the treatment of depression. Summary This article reviews the most important recent clinically relevant manuscripts in this rapidly expanding new field.

Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders

Vagus nerve stimulation is an interesting new approach to treating neuropsychiatric diseases within the class of brain-stimulation devices sometimes labeled ‘neuromodulators’. With vagus nerve stimulation, a battery-powered generator implanted in the chest wall connects to a wire wrapped around the vagus nerve in the neck, and sends intermittent pulses of electricity along the nerve directly into the brain. This mechanism takes advantage of the natural role of the vagus nerve in conveying information into the brain concerning homeostatic information (e.g., hunger, chest pain and respirations). Vagus nerve stimulation therapy is US FDA approved for the adjunctive treatment of epilepsy and has recently been FDA approved for the treatment of medication-resistant depression. Owing to its novel route into the brain, it has no drug–drug interactions or systemic side effects. This treatment also appears to have high long-term tolerability in patients, with low rates of patients relapsing on vagus nerve stimulation or becoming tolerant. However, alongside the excitement and enthusiasm for this new treatment, a lack of Class I evidence of efficacy in treating depression is currently slowing down adoption by psychiatrists. Much more research is needed regarding exactly how to refine and deliver the electrical pulses and how this differentially affects brain function in health and disease.

Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: An open label pilot study

Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33-36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD on day five (p = .01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed.

Interventional psychiatry: how should psychiatric educators incorporate neuromodulation into training?

ObjectiveInterventional psychiatry is an emerging subspecialty that uses a variety of procedural neuromodulation techniques in the context of an electrocircuit-based view of mental dysfunction as proximal causes for psychiatric diseases.MethodsThe authors propose the development of an interventional psychiatry-training paradigm analogous to those found in cardiology and neurology.ResultsThe proposed comprehensive training in interventional psychiatry would include didactics in the theory, proposed mechanisms, and delivery of invasive and noninvasive brain stimulation.ConclusionsThe development and refinement of this subspecialty would facilitate safe, effective growth in the field of brain stimulation by certified and credentialed practitioners within the field of psychiatry while also potentially improving the efficacy of current treatments.

Reward circuit DBS improves Parkinson's gait along with severe depression and OCD.

ABSTRACT A 59-year-old Caucasian man with a past history of Parkinson’s disease (PD) status post-bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), who also had treatment-resistant (TR) obsessive–compulsive disorder (OCD), and treatment-resistant depression (TRD), presented for further evaluation and management of his TR OCD. After an unsuccessful attempt to treat his OCD by reprogramming his existing STN DBS, he was offered bilateral ventral capsule/ventral striatum (VC/VS) DBS surgery. In addition to the expected improvement in OCD symptoms, he experienced significant improvement in both PD-related apathy and depression along with resolution of suicidal ideation. Furthermore, the patient’s festinating gait dramatically improved. This case demonstrates that DBS of both the STN and VC/VS appears to have an initial signal of safety and tolerability. This is the first instance where both the STN and the VC/VS DBS targets have been implanted in an individual and the first case where a patient with PD has received additional DBS in mood-regulatory circuitry.

Expanded Safety and Efficacy Data for a New Method of Performing Electroconvulsive Therapy: Focal Electrically Administered Seizure Therapy.

Objective Electroconvulsive therapy (ECT) is the most rapid and effective antidepressant treatment but with concerns about cognitive adverse effects. A new form of ECT, focal electrically administered seizure therapy (FEAST), was designed to increase the focality of stimulation and better match stimulus parameters with neurophysiology. We recently reported on the safety and feasibility of FEAST in a cohort (n = 17) of depressed patients. We now report on the safety, feasibility, preliminary efficacy, and cognitive effects of FEAST in a new cohort. Methods Open-label FEAST was administered to 20 depressed adults (6 men; 3 with bipolar disorder; age 49.1 ± 10.6 years). Clinical and cognitive assessments were obtained at baseline and end of course. Time to orientation recovery was assessed at each treatment. Nonresponders switched to conventional ECT. Results Participants tolerated the treatment well with no dropouts. Five patients (25%) transitioned from FEAST to conventional ECT due to inadequate response. After FEAST (mean, 9.3 ± 3.5 sessions; range, 4–14), there was a 58.1% ± 36.0% improvement in Hamilton Rating Scale for Depression scores compared with that in the baseline (P < 0.0001); 13 (65%) of 20 patients met response criteria, and 11 (55%) of 20 met remission criteria. Patients achieved reorientation (4 of 5 items) in 4.4 ± 3.0 minutes (median, 4.5 minutes), timed from eyes opening. There was no deterioration in neuropsychological measures. Conclusions These findings provide further support for the safety and efficacy of FEAST. The remission and response rates were in the range found using conventional ECT, and the time to reorientation may be quicker. However, without a randomized comparison group, conclusions are tentative.