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.

The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial.

BACKGROUND: Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) over several weeks is an FDA approved treatment for major depression. Although rTMS is generally safe when administered using the FDA guidelines, there are a number of side effects that can make it difficult for patients to complete a course of rTMS. Many patients report that rTMS is painful, although patients appear to accommodate to the initial painfulness. The reduction in pain is hypothesized to be due to prefrontal stimulation and is not solely explained by accommodation to the stimulation. METHODS: In a recent 4 site randomized controlled trial (using an active electrical sham stimulation system) investigating the antidepressant effects of daily left dorsolateral prefrontal rTMS (Optimization of TMS, or OPT-TMS), the procedural painfulness of TMS was assessed before and after each treatment session. Computerized visual analog scale ratings were gathered before and after each TMS session in the OPT-TMS trial. Stimulation was delivered with an iron core figure-8 coil (Neuronetics) with the following parameters: 10 Hz, 120% MT (EMG-defined), 4 s pulse train, 26 s inter-train interval, 3000 pulses per session, one 37.5 min session per day. After each session, procedural pain (pain at the beginning of the TMS session, pain toward the middle, and pain toward then end of the session) ratings were collected at all 4 sites. From the 199 patients randomized, we had usable data from 142 subjects for the initial 15 TMS sessions (double-blind phase) delivered over 3 weeks (142 × 2 × 15 = 4260 rating sessions). RESULTS: The painfulness of real TMS was initially higher than that of the active sham condition. Over the 15 treatment sessions, subjective reports of the painfulness of rTMS (during the beginning, middle and end of the session) decreased significantly 37% from baseline in those receiving active TMS, with no change in painfulness in those receiving sham. This reduction, although greatest in the first few days, continued steadily over the 3 weeks. Overall, there was a decay rate of 1.56 VAS points per session in subjective painfulness of the procedure in those receiving active TMS. DISCUSSION: The procedural pain of left, prefrontal rTMS decreases over time, independently of other emotional changes, and only in those receiving active TMS. These data suggest that actual TMS stimulation of prefrontal cortex maybe related to the reduction in pain, and that it is not a non-specific accommodation to pain. This painfulness reduction softly corresponds with later clinical outcome. Further work is needed to better understand this phenomenon and whether acute within-session or over time painfulness changes might be used as short-term biomarkers of antidepressant response.

Decreasing procedural pain over time of left prefrontal rTMS for depression: initial results from the open-label phase of a multi-site trial (OPT-TMS).

BACKGROUND: There is much interest in whether daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) over several weeks may become a clinically useful antidepressant treatment. Although rTMS appears largely safe, many patients report that this procedure is somewhat painful, which may restrict its ultimate appeal and utility. We analyzed interim results from the open-label phase of a multi-site randomized trial of rTMS as a treatment for depression to investigate whether the procedural pain of left prefrontal rTMS changes over time. METHODS: Patients with unipolar depression who had failed to respond during at least three weeks of the sham-controlled double-masked rTMS were then offered three more weeks (15 sessions) of open-label rTMS. Retrospective pain ratings and state emotional factors from 20 subjects were assessed using visual analog scales (VAS) recorded on computers before and after each treatment (289 sessions). RESULTS: Over the 15 treatment sessions, subjective reports of the painfulness of rTMS decreased 48% from baseline. This reduction, although greatest in the first few days, continued steadily (average 2.11 points per session) over the 3 weeks of treatment. The analysis found a significant effect for rTMS-session (p<0.0001) on rTMS-procedural pain over and above changes in subjective emotional states. CONCLUSION: The procedural pain of left, prefrontal rTMS decreases over time, apparently independently of other emotional changes. Since rTMS scalp pain may decline over time, physicians and patients may decide to continue treatment despite initial discomfort. These observational data can be better tested once the data from the blinded phase of the trial becomes available.

Controversy: Repetitive transcranial magnetic stimulation or transcranial direct current stimulation shows efficacy in treating psychiatric diseases (depression, mania, schizophrenia, obsessive-complusive disorder, panic, posttraumatic stress disorder).

Brain imaging studies performed over the past 20 years have generated new knowledge about the specific brain regions involved in the brain diseases that have been classically labeled as psychiatric. These include the mood and anxiety disorders, and the schizophrenias. As a natural next step, clinical researchers have investigated whether the minimally invasive brain stimulation technologies (transcranial magnetic stimulation [TMS] or transcranial direct current stimulation [tDCS]) might potentially treat these disorders. In this review, we critically review the research studies that have examined TMS or tDCS as putative treatments for depression, mania, obsessive-complusive disorder, posttraumatic stress disorder, panic disorder, or schizophrenia. (Separate controversy articles deal with using TMS or tDCS to treat pain or tinnitus. We will not review here the large number of studies using TMS or tDCS as research probes to understand disease mechanisms of psychiatric disorders.) Although there is an extensive body of randomized controlled trials showing antidepressant effects of daily prefrontal repetitive TMS, the magnitude or durability of this effect remains controversial. US Food and Drug Administration approval of TMS for depression was recently granted. There is much less data in all other diseases, and therapeutic effects in other psychiatric conditions, if any, are still controversial. Several issues and problems extend across all psychiatric TMS studies, including the optimal method for a sham control, appropriate coil location, best device parameters (intensity, frequency, dosage, and dosing schedule) and refining what subjects should be doing during treatment (activating pathologic circuits or not). In general, TMS or tDCS as a treatment for most psychiatric disorders remains exciting but controversial, other than prefrontal TMS for depression.