Susan McQueen

A Randomized Trial of rTMS Targeted with MRI Based Neuro-Navigation in Treatment-Resistant Depression

The aim of this study is to investigate whether repetitive transcranial magnetic stimulation (rTMS) targeted to a specific site in the dorsolateral prefrontal cortex (DLPFC), with a neuro-navigational method based on structural MRI, would be more effective than rTMS applied using the standard localization technique. Fifty-one patients with treatment-resistant depression were randomized to receive a 3-week course (with a potential 1-week extension) of high-frequency (10 Hz) left-sided rTMS. Thirty trains (5 s duration) were applied daily 5 days per week at 100% of the resting motor threshold. Treatment was targeted with either the standard 5 cm technique (n=27) or using a neuro-navigational approach (n=24). This involved localizing the scalp location that corresponds to a specific site at the junction of Brodmann areas 46 and 9 in the DLPFC based on each individual subjects MRI scan. There was an overall significant reduction in the Montgomery–Asberg Depression Rating Scale scores over the course of the trial, and a better outcome in the targeted group compared with the standard localization group at 4 weeks (p=0.02). Significant differences were also found on secondary outcome variables. The use of neuro-navigational methods to target a specific DLPFC site appears to enhance response to rTMS treatment in depression. Further research is required to confirm this in larger samples, or to establish whether an alternate method based on surface anatomy, including measurement from motor cortex, can be substituted for the standard 5 cm method.

A double blind randomized trial of unilateral left and bilateral prefrontal cortex transcranial magnetic stimulation in treatment resistant major depression

OBJECTIVE A substantive body of research has demonstrated the efficacy of repetitive transcranial magnetic stimulation treatment (rTMS) in patients with depression. However, the parameters needed to optimize therapeutic efficacy remain unclear. The aim of this study was to investigate whether there is an advantage in efficacy of sequential bilateral rTMS compared to standard high-frequency left sided rTMS. METHOD Sixty seven patients with treatment resistant depression were included in a randomised double-blind sham controlled trial of sequential bilateral rTMS compared to standard high-frequency left sided rTMS and sham rTMS over a three-week period. The study also included a further three week comparison of the two active treatment conditions. The primary outcome variable was scores on the 17-item Hamilton Depression Rating Scale (HAMD). RESULTS In the three-week double-blind phase of the trial there was a greater antidepressant response to unilateral left sided rTMS compared with sham or bilateral rTMS. Across the full six weeks of active rTMS, there was also a consistent pattern of improved response in unilateral left compared to bilateral treatment. Response rates were low in both active groups. CONCLUSIONS This study does not support the hypothesis that sequential bilateral rTMS is more effective than unilateral high-frequency left-sided rTMS.

A study of the effectiveness of bilateral transcranial magnetic stimulation in the treatment of the negative symptoms of schizophrenia

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is increasingly being investigated as a potential treatment for a number of psychiatric disorders, including schizophrenia. Previous rTMS studies have targeted the left-side prefrontal cortex (PFC) in the treatment of negative symptoms, with inconsistent findings. Some imaging evidence suggests right-sided or bilateral PFC involvement in negative symptoms, areas yet to be investigated for rTMS treatment. The study therefore aimed to assess the efficacy of bilateral high-frequency rTMS in the treatment of negative symptoms. METHODS A 2-arm double-blind randomized controlled trial was conducted with 20 patients with a diagnosis of schizophrenia or schizoaffective disorder, and moderate-to-severe treatment-resistant negative symptoms. Participants received a 3-week course of high-frequency bilateral rTMS or sham. Twenty trains (5 seconds duration) of 10 Hz rTMS at 110% of the RMT were administered to each PFC daily, 5 days a week. RESULTS No significant group or time differences in the Scale for the Assessment of Negative Symptoms (SANS) scores or cognitive outcomes were evident. However, a trend for greater reduction in scores on the autistic preoccupation scale of the Positive and Negative Symptom Scale for the active group compared to the sham group was observed (P = .05). CONCLUSIONS No substantial benefit of high-frequency bilateral rTMS was seen in the treatment of the negative symptoms of schizophrenia. Further research is required to explore whether rTMS may have benefits specific to particular cognitive or symptom domains.

A Negative Pilot Study of Daily Bimodal Transcranial Direct Current Stimulation in Schizophrenia

BACKGROUND A small number of studies conducted to date have suggested that transcranial direct current stimulation (tDCS) applied to the temporoparietal cortex may reduce auditory hallucinations in patients with schizophrenia. Prefrontal brain stimulation with other methods, has also been shown to potentially improve the negative symptoms of this disorder. OBJECTIVE To investigate the therapeutic potential of daily bimodal tDCS: anodal stimulation to the prefrontal cortex and cathodal stimulation to the temporoparietal junction in patients with persistent hallucinations and negative symptoms of schizophrenia. METHODS We conducted two small randomized double-blind controlled trials comparing bimodal tDCS to sham stimulation. In one study, stimulation was provided unilaterally, in the second study it was provided bilaterally. RESULTS Neither unilateral nor bilateral tDCS resulted in a substantial change in either hallucinations or negative symptoms. Stimulation was well tolerated without side-effects. CONCLUSION Daily tDCS does not appear to have substantial potential in the treatment of hallucinations or negative symptoms and further research should investigate higher doses of stimulation or more frequently applied treatment schedules.

Volumetric, cortical thickness and white matter integrity alterations in bipolar disorder type I and II.

BACKGROUND Bipolar disorder (BD) is a debilitating psychiatric disorder affecting millions of people worldwide with mean time to diagnosis estimated to be at least 10 years. Whilst many brain imaging studies have compared those with BD to controls, few have attempted to investigate differences between BD Type I and II and matched controls. METHODS Thirty-one patients with BD (16 Type I and 15 Type II) and 31 matched healthy controls were MRI brain scanned with conventional T1-weighted and diffusion tensor imaging methods. RESULTS There was significantly reduced regional brain volume and thickness among the BD subjects, but also between BD Type I when compared to Type II. White matter integrity also differed between the groups and BD severity correlated significantly with regional brain volume and thickness. LIMITATIONS Future investigations will consider length of time each BD patient had been diagnosed with BD, as well as assessing controls for family history of psychiatric illness, specifically BD. Similarly, genetic assessment will be conducted as well. CONCLUSIONS These findings suggest that there are not only regional brain volumetric, thickness and white matter integrity differences between BD and matched controls, but also between those with BD Type I and Type II, such that reduced regional brain volume may underlie BD Type I whereas white matter integrity is more altered in BD Type II.

A study of the effectiveness of high-frequency left prefrontal cortex transcranial magnetic stimulation in major depression in patients who have not responded to right-sided stimulation

The objective of this study was to explore the response rate to high-frequency left-sided repetitive transcranial magnetic stimulation (rTMS) in patients who had failed to respond to right-sided low-frequency stimulation, and to investigate whether there was differential efficacy between stimulation at 5 or 10 Hz. Data from two randomized controlled trials were pooled. In both studies a group of patients were randomized to receive either 5- or 10-Hz left prefrontal rTMS after failing to respond to right-sided stimulation. These patients received blinded 5- or 10-Hz stimulation (but without a sham control) for a period of up to 4 weeks and outcomes were compared. There was a small but significant overall response to left-sided rTMS but no difference in response between the 5- and 10-Hz treatment conditions. There appears to be a significant but modest likelihood of response to left-sided TMS in patients who fail right-sided stimulation, but there is no difference in efficacy between 5- and 10-Hz stimulation.

Transcranial magnetic stimulation for depression after a traumatic brain injury: a case study.

Depression after a traumatic brain injury (TBI) is very common, yet there is a lack of evidence-based treatment options for people who experience depression after a TBI. Traditionally, a history of TBI has been considered an exclusion criterion for transcranial magnetic stimulation trials because of the increased risk of seizure after a TBI. We present what we believe to be the first case of a patient with depression after a TBI treated with transcranial magnetic stimulation.

A negative double-blind controlled trial of sequential bilateral rTMS in the treatment of bipolar depression

BACKGROUND/OBJECTIVE To explore the therapeutic benefit of sequential bilateral repetitive transcranial magnetic stimulation (rTMS) in the treatment of bipolar depression. METHOD A 2 arm randomized controlled parallel design trial comparing the use of active sequential bilateral rTMS to a sham form of stimulation in 49 patients with bipolar disorder and treatment resistant depression. RESULTS There was no significant difference in mean reduction in depression rating scale scores or response rates between active and sham stimulation. LIMITATIONS The study was of limited sample size and the use of bilateral rTMS limited generalizability to other forms of rTMS. CONCLUSIONS This study provides no support to the use of active sequential bilateral rTMS in the treatment of the depressive phase of bipolar affective disorder. Although this result is not definitive, we suggest that future research may be better focused on trials evaluating the use of unilateral types of rTMS.

Exploring alternative rTMS strategies in non-responders to standard high frequency left-sided treatment: A switching study

BACKGROUND High-frequency left-sided repetitive transcranial magnetic stimulation (rTMS) is now commonly used treatment for patients with depression. However, there are several other forms of rTMS (low-frequency right-sided and sequential bilateral rTMS) which have also been shown to be effective. No information has been systematically gathered on the likelihood of response to alternative forms of rTMS in patients who do not improve after an initial course of left-sided treatment. OBJECTIVE To evaluate whether there are differences in antidepressant response between switching to either low-frequency right sided or sequential bilateral stimulation or continuing high-frequency left-sided TMS following non-response to an initial course of high-frequency left-sided rTMS. METHODS 113 rTMS naïve patients were provided with an initial three-week course of high-frequency left-sided rTMS. Non-responders were then randomised to receive another three weeks of left-sided treatment (n = 21), right-sided low frequency stimulation (n = 18) or sequential bilateral rTMS (n = 20). RESULTS Although there was an overall improvement in depressive symptoms in the randomised phase of the study, no significant differences in response was seen between the three treatment groups on Montgomery Asberg Depression Rating Scale or Hamilton Depression Rating Scale scores. LIMITATIONS The main limitation of the study was the duration of treatment provided in both the lead in and random treatment phases. CONCLUSION This study does not provide evidence for differences in response to different forms of rTMS in initial non-responders to left-sided stimulation. However, further studies with longer periods of treatment and a larger sample size are required to definitively establish or exclude between group differences in rTMS response in initial non-responders to treatment.

A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and electroconvulsive therapy in persistent depression

Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high‐powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment.