Double-blind, randomized sham controlled study of deep-TMS add-on treatment for negative symptoms and cognitive deficits in schizophrenia

Abstract

Negative symptoms and cognitive deficits are considered core symptoms of schizophrenia, yet treatment for them remains inadequate. Deep-transcranial magnetic stimulation (TMS) is a novel technology that enables non-invasive stimulation of deep layers of the prefrontal cortex. Preliminary evidence suggests that deep-TMS could be effective in the treatment of negative symptoms and cognitive deficits. The current study is the first double-blind, randomized sham-controlled study to examine the feasibility of deep-TMS add-on treatment for negative symptoms and cognitive deficits in schizophrenia. Twenty daily H1 deep-TMS treatments (20Hz, 120% MT) were delivered, in a double-blind, randomized sham-controlled design (n=30). Extensive clinical and cognitive assessments were carried out throughout the study and for an additional one month follow-up period. The results indicate that at the end of the treatment period, negative symptoms (as indicated by the Scale for the Assessment of Negative Symptoms (SANS)) significantly reduced in the TMS group (-7.7), but not in the sham group (-1.9). Differences between the groups were not statistically significant.

Repetitive Noninvasive Brain Stimulation to Modulate Cognitive Functions in Schizophrenia: A Systematic Review of Primary and Secondary Outcomes

“…Studies with a double-blind design that had cognitive measures as secondary outcomes could principally not overserve a beneficial effect of active stimulation compared to sham stimulation. 9,22,26,27,30,34,36,41,45 Other studies 33,35,37,50 indicate a potential benefit of active neurostimulation applied to the DLPFC on verbal memory, source monitoring, cognitive flexibility, or verbal fluency, whereas the aforementioned negative studies failed to show a benefit in the same or related domains. Interestingly, one study using high-frequency rTMS applied to the left DLPFC focused on the safety effect of frontal neurostimulation and did not reveal any potential harmful effect on cognition.…”

“…A total of 2155 records were excluded after screening of titles, abstracts, and article format reviews, resulting in 76 full texts that could then be retrieved. Of these 76 full texts, 5 were not detected through our search strategy [22][23][24][25][26] and included via other sources and targeted manual search. These 76 full-text articles were then analyzed regarding the presentation of any cognitive measures before and after NIBS intervention.…”

“…These 76 full-text articles were then analyzed regarding the presentation of any cognitive measures before and after NIBS intervention. In total, 33 primary studies published between 1999 and 2015 9,[13][14][15]22,23, were included for further analyses in this systematic review. All other full texts (N = 43) were excluded due to the lacking presentation of cognitive measures.…”

“…40,44,47,52 Out of these 4 studies, one used the Cambridge Neuropsychological Test Automated Battery (CANTAB), 40 one focused on working memory using a silent phonemic Verbal Fluency Task, 44 one focused also on working memory using a verbal n-back task, 47 and one used the MATRICS Consensus Cognitive Battery (MCCB). 52 The remaining 29 studies had global symptoms (N = 12), 13 22 However, as the latter study used the Brainsway H1 deep-TMS coil, 22 one could speculate that the built-in sham mode has been used. For tDCS, 3 trials used different variations of the ramp-up/ramp-down procedure, 41,48,52 but no study used the "built-in study-mode."…”

“…Only few studies included follow-up measures after the end of intervention. The longest followup periods were 8-12 weeks (for details, see 13 or in general 14,22,31,36,40,44,46,48 was an exclusion criterion in many studies. Other studies excluded the abuse/dependency 4 weeks, 15 3 months, 34 and 6 months prior to study inclusion.…”