Patrick Clarke

A randomized trial comparing repetitive transcranial magnetic stimulation given 3 days/week and 5 days/week for the treatment of major depression: Is efficacy related to the duration of treatment or the number of treatments?

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) has been shown to be an effective treatment for depression. However, there has been little research to determine optimal parameters for treatment. METHOD This study compared two rTMS treatment regimes for the treatment of major depression. Seventy-seven participants were randomized to either spaced or daily treatment. Spaced rTMS was given 3 days/week for 6 weeks (18 treatments in total) and daily rTMS was given 5 days/week for 4 weeks (20 treatments in total). All participants were assessed at baseline and after 4 weeks of treatment. Participants in the spaced treatment group were also assessed after 6 weeks of treatment. All participants were treated at 110% of the resting motor threshold with high-frequency rTMS (10 Hz) to the left dorsolateral prefrontal cortex (DLPFC) followed by low-frequency rTMS to the right DLPFC. RESULTS Participants in the daily treatment group showed more improvement by week 4 than those in the spaced treatment group; however, both groups had similar improvement by treatment completion. There was significant improvement in both groups in ratings of depression and anxiety, with no significant differences between groups. CONCLUSIONS Our study indicates that the efficacy of rTMS is related to the number of treatments given and that spacing the treatments neither improves nor reduces efficacy.

Practical considerations in the use of ultrabrief ECT in clinical practice.

Objective Electroconvulsive therapy (ECT) is the most effective treatment for major depression. Brief pulse width (BPW; pulse width, 1.0 m/s) ECT is often associated with cognitive impairment. Ultrabrief (UB; pulse width, 0.3 m/s) ECT is better tolerated and causes less cognitive impairment so has been introduced as an alternative. Previous research has shown that more treatments are needed with UB ECT; however, there has not been any previous research into the impact of prescribing UB ECT on length of stay. Methods This study reports naturalistic data collected from 258 inpatients in a private psychiatric hospital for 2 years since the introduction of UB ECT. Clinician and self-rated scales of depression severity and hospital service data were used to evaluate the number of ECT treatments, length of stay, and efficacy. Results Patients prescribed UB ECT had, on average, 10.9 treatments compared to 8.8 for BPW ECT. They also spent more time in hospital; 30.3 days from the first ECT treatment to discharge compared to 24.7 days for patients prescribed BPW ECT. Excluding patients who switched treatments, 54% of patients prescribed UB ECT responded compared to 66.7% of patients prescribed BPW ECT. More patients (n = 42) switched from UB to BPW than from BPW to UB (n = 3). In the 4 years since the introduction of UB ECT, the number of patients prescribed ECT has increased, and the mean number of treatments per patient (for all patients receiving ECT) has increased from 7.7 to 11.6. Conclusions Ultrabrief ECT has significant advantages, reflected in the increased use of ECT since UB ECT became available. However, the greater number of treatments and the increased length of stay have important implications for service delivery, costs, and bed accessibility.

Assessing the Effects of Repetitive Transcranial Magnetic Stimulation on Cognition in Major Depressive Disorder Using Computerized Cognitive Testing.

Objectives A range of different treatment approaches are available for depression; however, there is an ongoing concern about the cognitive impairment associated with many treatments. This study investigated the effect of treatment with repetitive transcranial magnetic stimulation (rTMS) on cognition in patients with major depressive disorder. Cognition before and after treatment was assessed using a computerized cognitive testing battery, which provided comprehensive assessment across a range of cognitive domains. This was a naturalistic study involving patients attending an outpatient clinical rTMS service. Methods A total of 63 patients with treatment-resistant depression completed the IntegNeuro cognitive test battery, a well-validated comprehensive computerized assessment tool before and after receiving 18 or 20 treatments of sequential bilateral rTMS. Change in the various cognitive domains was assessed, and analyses were undertaken to determine whether any change in cognition was associated with a change in rating of depression severity. Results There was a significant decrease in Hamilton Depression Rating Scale scores from baseline to posttreatment. There was no decline in performance on any of the cognitive tests. There were significant improvements in maze completion time and the number of errors in the maze task. However, these were accounted for by improvement in mood when change in depressive symptoms was included as a covariate. Conclusions This open-label study provides further support for the efficacy and safety of rTMS as a treatment option for people with major depressive disorder in a naturalistic clinical setting. Using a comprehensive, robust computerized battery of cognitive tests, the current study indicated that there was no significant cognitive impairment associated with rTMS and that any improvements in cognitive functioning were associated with a reduction in depressive symptoms.

How safe is repetitive Transcranial Magnetic Stimulation

There is considerable support for the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of depression (Gaynes et al., 2014). However, there is less literature available regarding its safety in clinical use. We report data from an rTMS clinical service operating since August 2008 (see Galletly et al., 2010). In seven years of operation, both bilateral and unilateral treatment protocols were used. In unilateral treatments, continuous low frequency (1Hz) rTMS was applied to the right dorsolateral prefrontal corte (DLPFC) for 15 minutes, whilst bilateral treatments also included intermittent high frequency rTMS (10Hz) applied to the left DLPFC for 15 minutes. All treatment intensities were delivered at 110% of the motor threshold using a MagPro R30 machine and MCF B65 figure-of-eight coil (MagVenture A/S, Denmark). In acute courses, either 18 or 20 treatments were administered over six or four weeks respectively, whilst maintenance treatments were delivered every one to four weeks. Patients were offered earplugs, or listened to relaxation or mindfulness recordings, during treatment. Two hundred and five individual patients have been treated, 45 more than once (262 courses in total). There have been a total of 6,155 rTMS treatments; 5,008 (81.4%) acute course treatments, and 1,147 (18.6%) maintenance treatments. There were no serious adverse events – in particular, there have been no seizures and no manic episodes associated with rTMS. More than two thirds of patients (69.4%) indicated that they experienced no side-effects. Only 4.3% reported side-effects that were severe enough to interfere with functioning, with just one patient indicating that the therapeutic benefit was outweighed by the side-effects experienced. The remaining patients said they were aware of side-effects but that these did not interfere with functioning. Consistent with the literature (Rossi et al., 2009), the side-effects commonly reported were mild, mostly localised discomfort at the site of stimulation and headaches. Some patients also reported tiredness following treatment sessions. Discomfort at the site was addressed by reducing the intensity of the stimulus. Overall, only 8.0% of patients dropped out before completing their course, often because of side-effects or lack of efficacy. One patient cited nausea and dizziness as the reason. Patients were referred by their treating psychiatrists, and people with comorbid medical conditions (except epilepsy) were not excluded. People with psychiatric comorbidities, other than drug and alcohol use disorders, were also accepted for treatment. The present report therefore provides naturalistic Australian data about the safety of rTMS, in a clinical setting. Drop-out rates and incidences of troublesome side-effects were low, and treatment was generally well accepted.

A clinical repetitive transcranial magnetic stimulation service in Australia: 6 years on.

Objective: There is considerable research evidence for the effectiveness of repetitive transcranial magnetic stimulation in the treatment of depression. However, there is little information about its acceptability and outcomes in clinical settings. Method: This naturalistic study reports on a clinical repetitive transcranial magnetic stimulation service that has been running in Adelaide, South Australia (SA), for 6 years. During this time, 214 complete acute courses were provided to patients with treatment-resistant Major Depressive Disorder. Patients received either sequential bilateral or right unilateral repetitive transcranial magnetic stimulation treatment involving either 18 or 20 sessions given over 6 or 4 weeks respectively. Data included patient demographic details, duration of depression, and medication at the beginning of their repetitive transcranial magnetic stimulation course. The Hamilton Depression Rating Scale was used to assess response to repetitive transcranial magnetic stimulation. Results: Of those undergoing a first-time acute treatment course of repetitive transcranial magnetic stimulation (N = 167), 28% achieved remission, while a further 12% met the criteria for a response to treatment. Most patients (N = 123, 77%) had previously been treated with five or more antidepressant medications, and 77 (47%) had previously received electroconvulsive therapy. Referral rates remained high over the 6 years, indicating acceptance of the treatment by referring psychiatrists. There were no significant adverse events, and the treatment was generally well tolerated. In all, 41 patients (25%) had a second course of repetitive transcranial magnetic stimulation and 6 (4%) patients had a third course; 21 patients subsequently received maintenance repetitive transcranial magnetic stimulation. Conclusion: This naturalistic study showed that repetitive transcranial magnetic stimulation was well accepted by both psychiatrists and patients, and has good efficacy and safety. Furthermore, repetitive transcranial magnetic stimulation can provide a useful treatment alternative as part of outpatient mental health services for people with depression.

A Practical Guide to Setting up a Repetitive Transcranial Magnetic Stimulation (rTMS) Service

Objective: This paper outlines the process of developing a transcranial magnetic stimulation (rTMS) service in a private hospital setting, to provide a model for similar services elsewhere in Australia and New Zealand. Methods: The practical issues involved in setting up the service, including funding, staffing, equipment, treatment protocols and associated research, are described. Results: The service has been widely accepted by psychiatrists and patients. Forty-five patients have completed treatment and the research results show a significant clinical response to rTMS. Conclusions: Clinicians involved in the service have found both the clinical and research components rewarding. In the longer term, the issue of ongoing funding of rTMS services remains to be resolved.

Telepsychiatry in South Australia

South Australia has a population of about 1.5 million, of whom one million live in Adelaide, the state capital. All except one of the states 160 practising psychiatrists live in Adelaide or adjacent rural and semi-rural locations. Historically, professional and geographical isolation and lack of facilities have prevented psychiatrists from living and working outside the metropolitan environment.

A Comparison of Right Unilateral and Sequential Bilateral Repetitive Transcranial Magnetic Stimulation for Major Depression: A Naturalistic Clinical Australian Study.

Background A great deal of research has established the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. However, questions remain about the optimal method to deliver treatment. One area requiring consideration is the difference in efficacy between bilateral and unilateral treatment protocols. Objective This study aimed to compare the effectiveness of sequential bilateral rTMS and right unilateral rTMS. Methods A total of 135 patients participated in the study, receiving either bilateral rTMS (N = 57) or right unilateral rTMS (N = 78). Treatment response was assessed using the Hamilton depression rating scale. Results Sequential bilateral rTMS had a higher response rate than right unilateral (43.9% vs 30.8%), but this difference was not statistically significant. This was also the case for remission rates (33.3% vs 21.8%, respectively). Controlling for pretreatment severity of depression, the results did not indicate a significant difference between the protocols with regard to posttreatment Hamilton depression rating scale scores. Conclusions The current study found no statistically significant differences in response and remission rates between sequential bilateral rTMS and right unilateral rTMS. Given the shorter treatment time and the greater safety and tolerability of right unilateral rTMS, this may be a better choice than bilateral treatment in clinical settings.

Does rTMS reduce depressive symptoms in young people who have not responded to antidepressants

Depression is common in young people, and there is a need for safe, effective treatments. This study examined the efficacy of repetitive transcranial magnetic stimulation in a sample of young people aged 17 to 25 years.