A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience
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[ 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 17 percent motor threshold in a sham- controlled trial of 35 individuals with chronic schizophrenia. In a group of 22 chronic, hospitalized patients with schizophrenia, high frequency TMS was not found to have a therapeutic effect. 39 Novak et al 40 in 2006 were unable to show that high frequency TMS over the left dorsolateral prefrontal cortex would reduce negative symptoms in 16 patients with schizophrenia who had predominant negative symptoms and were stabilzed on antipsychotic medication. This study only used 90- percent motor threshold with a total of 2000 stimuli per session. Although Mogg et al 41 did not see improvement in negative symptoms, they did see some improvement in cognitive function in their study of 17 right- handed patients with schizophrenia who were treated with TMS. In a two-armed, double-blind, randomized, controlled trial, Fitzgerald et al 24 investigated the efficacy of bilateral high frequency TMS to treat moderate-to-severe, treatment-resistant negative symptoms in 20 patients with schizophrenia or schizoaffective disorder. The authors found no substantial benefit. This study used bilateral high frequency TMS as compared to many trials where TMS is used unilaterally. Also, this study had a three-week treatment period, which may be too short of a course for longstanding negative symptoms of schizophrenia. Meta-analyses. Opinions vary as to the effectiveness of high frequency TMS in treating negative symptoms of schizophrenia. A meta- analysis completed in 2009 that included eight studies of high frequency (10Hz) stimulus applied to the left dorsolateral prefrontal cortex in patients with schizophrenia showed an effect size of 0.58. When three open-label trials were excluded from analysis, the effect size for the controlled studies dropped to 0.27. This was appropriately interpreted by the authors as a marginal effect. A second meta-analysis examined seven controlled studies of high frequency to the left dorsolateral prefrontal cortex in patients with schizophrenia and reported an effect size of 0.63. 42 As effect sizes for antipsychotic medication treatment of negative symptoms range from 0.17 to 0.21, those of TMS ranging from 0.27 to 0.63 are encouraging. TABLE 2. TMS treatment for negative symptoms in schizophrenia AUTHOR/DATE N LOCATION % MT HERTZ # OF PULSES RESULTS OF STUDY COIL TYPE Rollnick/2000 12 Left DLPFC 80 20 8000 Positive BPRS ratings for active vs. sham subjects Figure of Eight Hajak/2004 20 Left DLPFC 110 10 10,000 CDSS showed improvement of n egative symptoms Figure of E ight G oyal/2007 10 Left DLPFC 110 10 10,000 CDSS showed improvement in active group Figure of Eight Prikryl/2008 22 Left DLPFC 110 10 22500 25% reduction in PANSS in active group Figure of Eight Schneider/ 2008 17 Left DLPFC 110 10 20000 SANS score showed marked reduction in active group Figure of Eight Cordes/2010 35 Left DLPFC 110 10 10000 Only a subgroup of patients showed mild improvement in GAF Figure of Eight Holi/2004 22 Left DLPFC 100 10 10000 NO PANSS difference found between groups Figure of Eight Novak/2006 16 Left DLPFC 90 20 20000 NO PANSS difference found between groups Figure of Eight Fitzgerald/ 2008 20 BL DLPFC 110 10 15000 SANS did not show improvement in treated group Figure of Eight MT: motor threshold; PANSS: Positive and Negative Syndrome Scale; SANS: Scale for the Assessment of Negative Symptoms; SAPS: Scale for the Assessment of Positive Symptoms; MADRS: Montgomery-Asberg Depression Rating Scale; CDSS: Calgary Depression Scale for Schizophrenia; L DLPFC: left dorso-lateral prefrontal cortex; R&L; PFC: right and left prefrontal cortex