A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience
Issue link: https://innovationscns.epubxp.com/i/555782
[ V O L U M E 1 2 , N U M B E R 7 – 8 , J U L Y – A U G U S T 2 0 1 5 ] Innovations in CLINICAL NEUROSCIENCE 15 treated with standard antipsychotics following a 10-day experimental phase in which the experimental group received low frequency TMS o ver the left temporo-parietal cortex. Auditory hallucinations were significantly reduced in the experiemental group of patients. Vercammen et al 23 reported significant reduction in hallucination frequency in patients with schizophrenia who received TMS to the left temporo-parietal region, as well as a reduction in self-reported affective responsiveness in patients who received TMS to bilateral temporoparietal regions. There have also been a number of negative studies on the use of TMS in patients with schizophrenia. 24–28 Fitzgerald et al 24 did not find a difference in therapeutic effect in domains such as frequency, duration, location, intensity, and disruption of voices between the active and sham groups of 20 patients with either schizophrenia or schizoaffective disorder who suffered from moderate to severe treatment-resistant negative symptoms. However, they did report a significant reduction in the loudness of hallucinations. In 2006, Saba et al 25 treated 18 patients with schizophrenia and refractory auditory hallucinations with TMS for 10 days. TMS was applied over the left temporoparietal cortex with a stimulus of only 80-percent motor threshold. The authors reported no significant differences between the active and sham groups. Rosa et al 26 reported safe administration of TMS concurrently with clozapine in 11 patients with schizophrenia but did not reveal significant reduction in auditory hallucinations. A large randomized trial 27 in 2011 using fMRI to guide TMS treatment site failed to produce positive results in reducing severity of auditory hallucinations. This study involved 63 patients who specifically suffered from treatment- resistant auditory/visual hallucinations. In 2011, a study by DeJesus et al 28 was done using TMS on 17 patients with refractory schizophrenia who suffered from auditory hallucinations and were being treated with clozapine. The authors reported no significant r eduction in auditory hallucinations using TMS. In total, we found sixteen controlled studies and two open-label studies using low frequency TMS. 12–32 Of the randomized, controlled studies, 10 studies involving a total of 257 subjects with psychosis revealed positive results in treating auditory hallucinations with TMS, while eight studies involving a total of 284 subjects with psychosis did not show any efficacy using TMS. Meta-analyses. A meta-analysis done by Aleman et al 28 in 2007 analyzed data from 10 sham- controlled trials of low frequency TMS applied to treat auditory hallucinations in schizophrenia. Pre- versus post-treatment mean standardized effect size was reported 0.76, supporting a robust efficacy of this modality in reducing the severity of auditory hallucinations. A second meta-analysis on the same topic was done in 2009 by Freitas et al, 30 which further bolstered the evidence in support of using TMS to treat auditory hallucinations in schizophrenia. Pre- versus post- treatment effect within the two arms of treatment was 1.28. Similar to Aleman's findings, the effect size for sham-controlled studies was 1.04 (large treatment effect). Both analyses 29,30 provide evidence for a significant and robust effect on auditory hallucinations in patients with schizophrenia. TMS was used to stimulate the left temporo-parietal cortex at low frequencies. However, as we indicated above, when the broader literature base is taken into consideration, a total of 10 studies yielded positive results whereas eight did not. A systematic review done by Soltema 31 in 2013 compared 25 randomized, control trials using the severity of the hallucinations or psychosis as the primary outcome measure. No differences were seen with the severity of psychosis. The severity of hallucinations was significantly reduced with paradigm of left temporoparietal TMS at 1hz. Other paradigms were measured, and w ere unable to make a difference in hallucination severity. A review of controlled and uncontrolled studies in the treatment of auditory hallucinations using low frequency TMS to the left temporo- parietal cortex supports the hypothesis that TMS can reduce these symptoms. 1 2–32 Results vary across studies and this could be attributed to the heterogeneity of study methodology. There is some indication that the dose of TMS has some bearing on the efficacy. One out of three reviewed studies that used a dose of 80 percent of motor threshold showed positive results (33%) in reducing auditory hallucinations, while seven out of 12 reviewed studies that used 90 percent of MT dose (58%) and both of two reviewed studies (100%) that used a dose of 100 percent or more than motor threshold showed positive results in reducing auditory hallucinations. However, more data are necessary to understand the relationship between the dose of TMS and efficacy in treating auditory hallucinations. In addition, the other factors that are likely to impact the efficacy of TMS include treatment- resistant symptoms, use of associated medication, such as anticonvulsants. As TMS is a well tolerated treatment with no major complications or neurocognitive impairment, it is potentially an attractive treatment modality for treatment-resistant auditory hallucinations. Table 1 lists the reviewed literature on use of TMS for treatment of auditory hallucinations in schizophrenia. TMS for negative symptoms. Clinical studies. The treatment of negative symptoms of schizophrenia with high frequency TMS has shown significant results overall. Ten randomized, controlled trials are published in the literature (n=228 subjects), five of which have