Brief reportTheta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: Results of a randomized controlled study
Introduction
In patients with medication-resistant auditory verbal hallucinations (AVH), repetitive transcranial magnetic stimulation (rTMS) has been demonstrated as an effective therapy (Hoffman et al., 2003). A meta-analysis of 10 placebo-controlled TMS studies yielded a mean effect size of d=0.76 for AVH (Aleman et al., 2007). In the 2009 schizophrenia PORT guidelines (Buchanan et al., 2010), 1-Hz TMS is recommended as treatment for patients with AVH that have not responded to pharmacological treatments.
Even though there are several reports that question the effectiveness of rTMS for treatment of AVH (Slotema et al., 2011), a recent meta-analysis, controlling for publication bias, confirmed a reduced but significant effect size (Hedge index 0.41) (Demeulemeester et al., 2011).
A rTMS protocol that has recently been introduced into clinical research is theta burst stimulation (TBS) (Huang et al., 2005). TBS seems to induce plastic changes in cortical synapses in a long-term potentiation or long-tem depression-like fashion. It was shown that continuous TBS (cTBS) over the contralesional hemisphere reduces neglect in stroke patients for several hours (Nyffeler et al., 2009). Furthermore, the cTBS protocol has proven to be effective in language research (Kindler et al., 2012).
So far, there are three case reports applying cTBS in AVH (Eberle et al., 2010, Poulet et al., 2009, Sidhoumi et al., 2010), with one of them demonstrating a full response in a patient with chronic AHV after a 9-week bilateral continuous theta burst TMS treatment (Eberle et al., 2010). A larger clinical trial has not been published yet.
From a clinical point of view, cTBS has the advantage of a very short application duration (44 s), as compared to the often-used 1-Hz stimulation protocol (15 min) for the same number of pulses.
In conventional TMS studies, the left temporoparietal cortex (TP3 of the 10–20 international EEG system) served as the target region for TMS stimulation. Area Spt (Sylvian parietotemporal), located in the Sylvian fissure at the parietotemporal boundary, is a sensorimotor interface between the sensory and motor speech systems (Hickok and Poeppel, 2007). Recently we demonstrated that the functionally defined Area Spt is close to the conventionally targeted area TP3 (Kindler et al., 2013).
Here, we present a single-blind, controlled clinical trial comparing 1 Hz with cTBS treatment regarding clinical outcome variables.
Section snippets
Patients and clinical investigation
Participants comprised 24 patients (Table 1), with 12 patients receiving 1-Hz rTMS and 12 receiving cTBS. Inclusion criteria were diagnosis of schizophrenia or schizoaffective disorder (ICD-10), medication resistant AVH, age between 18 and 65 years, and right-handedness (assessed with the Edinburgh Handedness Scale (Oldfield, 1971)). Exclusion criteria were history of epileptic seizures, signs of elevated neuronal activity in electroencephalography (EEG), MR contraindications and medical
Results
In the collapsed group, mean age was 41.88 (±11.82) years, gender 14f (10m), PANSS 74.0 (±16.0), PsyRats 38.3 (±11.8), and AHRS 34.2 (±6.2). Three of the patients were diagnosed with schizoaffective disorder, 21 with schizophrenia. Nine (38%) patients fulfilled criteria of response.
The cTBS group showed a significantly higher PANSS score at baseline, whereas all other scores or variables did not differ significantly. Further, no difference was detected when evaluating improvement in AVH scores (
Discussion
This is the first randomized control, single-blind study comparing the classical 1-Hz and the cTBS protocol with respect to clinical outcome. The advantage of cTBS is the shorter application time and previously described longer duration of the effects compared with 1-Hz protocols (Nyffeler et al., 2009). However, in our sample we did not find significant differences between 1-Hz and and cTBS protocols. But notably, the cTBS paradigm was safe and effective with response rates comparable to the
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