A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience
Issue link: https://innovationscns.epubxp.com/i/555782
Innovations in CLINICAL NEUROSCIENCE [ 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 ] 14 stimulation, negative symptoms, positive symptoms, schizophrenia, and neuromodulation for the years 1996 to November 2013. Searches w ere conducted for original papers, reviews, and meta-analyses. A hand search for relevant publications was conducted using references of articles reviewed. Articles included in our analysis were randomized, controlled trials and meta-analyses, while individual case reports, case series, and opinion pieces were excluded. Our searches yielded a total of 45 papers. Of these, 31 were considered relevant, and all of these studies were included in our analysis. Articles that were not published in English were excluded. RESULTS TMS for positive symptoms. Clinical studies. In 2000, Hoffman et al 12 conducted a double-blind crossover study of 12 patients with schizophrenia. Patients received 1Hz TMS at 80 percent of the motor threshold over the left temporo- parietal cortex for 15 to 30 minutes. All of these patients remained on their antipsychotic medications, and their auditory hallucinations were assessed using the Positive and Negative Syndrome scale (PANSS). 13 Reductions in hallucination severity were found to be significant after active treatment as opposed to sham. Interestingly, it was noted that in patients on anticonvulsant medications, treatment effects were reduced. This could indicate the need for higher stimulus dose or a reduction or omission of anticonvulsants. Also the dosing here was infra-motor threshold, making it unlikely that the trial would be positive. 12 Hoffman et al extended their data further in 2003 with a double-blind, crossover trial 14 of 24 patients who received 1Hz TMS over the left temporo-parietal cortex at 90 percent motor threshold for 8 to 16 minutes over seven days while being maintained on their current psychotropic medications. Diverging from previous protocol, auditory hallucinations were assessed using the Hallucination Change Scale 14 as the primary measure. Seventy-five percent of the patients d emonstrated a positive response following the active phase of TMS compared to 17 percent in the sham phase. Patients also carried a counter to track hallucination frequency, for which the active group showed a linear decrease over time. For more than half of the patients in this trial, treatment effects lasted 15 weeks. 14 In 2004, McIntosh et al 15 attempted to replicate the results of the Hoffman et al 14 study. Sixteen patients received 1Hz TMS over the left temporo-parietal cortex at 80 percent motor threshold for 8 to 16 minutes for one week before crossing over to sham treatment and vice versa. Auditory hallucinations were evaluated using PANSS. Interestingly, 11 of these 16 patients had received clozapine in the past. No significant effect was found between the active treatment and sham groups. However, this population of patients, with known past treatment failures, may have been particularly resistant to treatment. In addition, the very small sample size indicates that this study was underpowered to detect a treatment effect between groups, and its design is subject to carryover effects. 15 In 2005, Poulet et al 16 replicated the study by McIntosh et al 15 supporting the use of TMS to treat auditory hallucinations. This study involved 10 patients with treatment- resistant auditory hallucinations in a double-blind crossover design. The active TMS treatment involved 1Hz TMS over the left temporo-parietal cortex with a stimulus of 90 percent of the motor threshold, receiving 10,000 stimuli over five days with a one-week washout before one week of sham treatment. Auditory hallucinations were assessed using the Auditory Hallucination Rating scale (AHRS), 17 which revealed a significant decrease in scores during the active phase as opposed to sham. There was a mean improvement in AHRS scores of 56 percent in five days. TMS at low frequency provided significant b enefit in reducing auditory hallucinations. The dose (i.e., pulses delivered) of TMS was higher than in previous trials. These findings were consistent with the Hoffman et al 14 study in 2003. Similar to Hoffman's findings, it was also noted that patients on anticonvulsant medications did not respond as well to treatment. 16 Between 2005 and 2007, a plethora of studies was published in the area of TMS treatment for auditory hallucinations. 1 8–23 Chibbaro et al 18 reported a significant long- term reduction in auditory hallucinations in 16 patients with schizophrenia. These patients were taking atypical antipsychotics and were treated with TMS, with a return to baseline in their sham group. In 2005, Lee et al 19 reported that both left- and right-sided TMS applied at low frequency significantly reduced auditory hallucinations in a group of 39 patients with schizophrenia and treatment-refractory auditory hallucinations. Brunelin et al 2 0 reported significant reduction in auditory hallucinations in 24 right- handed, treatment-refractory patients with schizophrenia who were treated with TMS. These patients were randomly selected into sham or active treatment groups for rTMS to the left temporoparietal cortex. In 2006, Jandl et al 21 conducted a randomized, crossover, sham-controlled trial of TMS over the left and right temporo-parietal cortex in 16 patients with auditory hallucinations but not necessarily schizophrenia. Five patients who only received treatment of the left hemisphere responded. Group mean hallucination scores did not differ across treatment conditions. Bagati et al 22 conducted a study in 2009 that included 40 patients with schizophrenia who were randomized to either an experimental group or a control group. Both groups were