Table 2.
Dorsolateral prefrontal cortex rTMS for the treatment of schizophrenia
| First author, year | Design | Control | Sample size | Frequency, %MT, sessions | Pulses per session | Side | Summary |
|---|---|---|---|---|---|---|---|
| Rollnik, 2000 | Double-blind, crossover | Tilted coil | 12 | 20 Hz, 80%, 10 | 800 | L | Improvements in BPRS |
| Holi, 2004 | Double-blind, randomized | Tilted coil | 22 | 10 Hz, 100%, 10 | 1000 | L | No between-group difference in PANSS; no significant change in MMSE or hormones (cortisol, prolactin, TSH) |
| Hajak, 2004 | Double-blind, randomized | Sham coil | 20 | 10 Hz, 110%, 10 | 1,000 | L | Improvement in PANSS negative scores, trend toward improved general and worse positive scores; no cerebral blood flow differences on ECD-SPECT |
| Novak, 2006 | Double-blind, randomized | Tilted coil | 16 | 20 Hz, 90%, 10 | 2,000 | L | No significant effect on PANSS, CGI, MADRS, neuropsychological testing; sham showed a trend toward improvement on positive and negative subscales of PANSS and MADRS; between-group comparisons showed a positive subscale of PANSS after 8 weeks |
| Mogg, 2007 | Double-blind, randomized | Sham coil | 17 | 10 Hz, 110%, 10 | 2,000 | L | No significant difference on PANSS negative scores; active rTMS group had better delayed recall on HVLT |
| Prikryl, 2007 | Double-blind, randomized | Tilted coil | 22 | 10 Hz, 110%, 15 | 1500 | L | Negative symptom improvement on PANSS and SANS |
| Goyal, 2007 | Double-blind, randomized | Tilted coil | 10 | 10 Hz, 110%, 10 | 980 | L | Inpatients without antipsychotic medication for past 2 months- active rTMS group improved negative symptoms on PANSS even when factoring out depressive symptoms with CDSS |
| Fitzgerald, 2008 | Double-blind, randomized | Tilted coil | 20 | 10 Hz, 110%, 15 | 1,000 per hemisphere | B/L | No difference of negative symptoms on SANS or cognitive outcomes on ST, COWAT, and TMT-A/B; trend toward reduction in autistic preoccupation component of PANSS |
| Schneider, 2008 | Double-blind, randomized | Coil cover for sham group | 17 | 1 Hz vs 10 Hz, 110%, 20 | 100 of 1 Hz, 1,000 of 10 Hz | L | 10 Hz group showed improved negative symptoms on SANS at weeks 4 and 8; trend toward improved WCST in 10 Hz group |
| Cordes, 2010 | Double-blind, randomized | Sham coil | 95 | 10 Hz, 110%, 10 | 1,000 | L | No change in PANSS, CGI, or GAF except subgroup with pronounced negative symptoms showed improvements in GAF |
| Mittrach, 2010 | Double-blind, randomized | Sham coil | 32 | 10 Hz, 110%, 10 | 1,000 | L | No effect on cognition based on TMT-A/B, WCST, D2 attention task, and KAI |
| Barr, 2012 | Double-blind, randomized | Tilted coil | 25 | 20 Hz, 90% MT, 20 | 750 per hemisphere | B/L | No improvement of negative symptoms on PANSS or SANS, or depression on CDSS |
| Prikyrl, 2012 | Double-blind, randomized | Sham coil | 30 | 10 Hz, 110%, 15 | 1500 | L | Improved negative and general psychopathology scores on PANSS; improved cognition based on VFT scores but not statistically significant |
| Prikryl, 2013 | Double-blind, randomized | Sham coil | 40 | 10 Hz, 110%, 15 | 2,000 | L | Improved negative symptoms on SANS |
| Guse, 2013 | Double-blind, randomized | Tilted coil | 25 | 10 Hz, 110%, 15 | 1,000 | L | No change in brain activation patterns seen on fMRI during VWMT or cognitive improvement based on TMT-A/B, TAP, WCST |
| Barr, 2013 | Double-blind, randomized | Tilted coil | 27 | 20 Hz, 90%, 20 | 750 per hemisphere | L/R | Cognition improved on n-back working memory task |
| Wolwer, 2014 | Double-blind, randomized | Sham coil | 35 | 10 Hz, 110%, 10 | 1,000 | L | Improved facial affect recognition assessed with 30 digitally reworked photographs of faces |
| Zhao, 2014 | Double-blind, randomized | Tilted coil | 96 |
iTBS,80%, 10 Hz, 20 Hz, 110%, 20 |
2,400 (iTBS) 1500 (10/20 Hz) |
Decreased PANSS negative and general psychopathology, SANS scores in iTBS, 10 Hz, 20 Hz groups. Decrease greater in iTBS compared to 10 and 20 Hz groups | |
| Quan, 2015 | Double-blind, randomized | Tilted coil | 117 | 10 Hz, 80%, 10 | 800 | L | Improved negative symptoms at end of treatment and 24 week follow up based on PANSS and SANS; no effect on CGI |
| Wobrock, 2015 | Double-blind, randomized | Tilted coil | 197 | 10 Hz, 110%, 15 | 1,000 | L | Small but significant improvement in positive symptoms on PANSS; no effect on negative symptoms on PANSS, depression on MADRS or CDSS, symptoms severity on CGI or GAF, or cognitive function on TMT-A/B |
| Dlabac-de lange, 2015 | Double-blind, randomized | Tilted coil | 32 | 10 Hz, 90%, 30 (2 times daily for 15 days) | 2,000 per hemisphere | L/R | Negative symptoms improved on SANS but not PANSS; no change in depressive symptoms on MADRS; cognitive improvement on VFT but not DSST, TMT- A/B, WCST, RAVL; insight improved based on BIS |
| Li, 2016 | Double-blind, randomized | Sham coil | 47 | 10 Hz, 110%, 20 | 1,500 | L | Decreased negative symptoms on SANS at 8 weeks but not 4 weeks |
| Kamp, 2016 | Randomized | Sham coil | 35 | 10 Hz, 110%, 10 | 1,000 | L | Decreased delta band activity thereby decreasing hypofrontality; trend towards a correlation between this and improvement of facial affect recognition |
| Hasan, 2016 | Double-blind, randomized | Tilted coil | 156 | 10 Hz, 110%, 15 | 1,000 | L | No cognitive improvement on RAVL, TMT-A/B, WCST, DST, RWFT |
| Hasan, 2017 | Double-blind, randomized | Tilted coil | 73 | 10 Hz, 110%, 15 | 1,000 | L | Significant correlations between left hippocampal, parahippocampal, and precuneal volume increases measured by MRI; negative symptom improvement on PANSS |
| Francis, 2019 | Double-blind, randomized | Sham coil | 20 | 20 Hz, 110%, 10 | 600 per hemisphere | B/L | Cognitive improvement based on BACS; no significant changes in cortical thickness; thicker L prefrontal cortex predicted greater improvement in cognitive function |
| Wagner, 2019 | Double-blind, randomized | Tilted coil | 26 | 10 Hz, 110%, 15 | 1,000 | L | Improved positive symptoms and general psychopathology PANSS scores in patients on clozapine |
MT motor threshold, L left, R right, B/L bilateral, L/R left then right, DLPFC dorsolateral prefrontal cortex, BACS Brief Assessment of Cognition in Schizophrenia, BIS Birchwood Insight Scale, BPRS Brief Psychiatric Rating Scale, CDSS Calgary Depression Scale for Schizophrenia, CGI Clinical Global Impression scale, COWAT Controlled Oral Word Association Test, DSST Digit Symbol Substitution Test, DST Digit Span Test, ECD-SPECT technetium-99 bicisate Single Photon Emission Computed Tomography, fMRI functional Magnetic Resonance Imaging, GAF Globalized Assessment of Functioning, HVLT Hopkins Verbal Learning Task, KAI Short test of general intelligence, MADRS Montgomery–Åsberg Depression Rating Scale, MMSE Mini-Mental Status Exam, PANSS Positive and Negative Syndrome Scale, RAVL Rey Auditory Verbal Learning Test, RWFT Regensburg Word Fluency Test, SANS Scale for the Assessment of Negative Symptoms, SAPS Scale for the Assessment of Positive Symptoms, ST Stroop Test, TAP Tübinger Aufmerksamkeitsprüfung (computer-based test battery) , iTBS Intermittent Theta Burst Stimulation, TMT- A/B Trail Making Test parts A and B, VFT Verbal Fluency Test, VWMT Verbal Working Memory Task, WCST Wisconsin Card Sorting Test