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ABSTRACTWe reviewed the literature on

transcranial magnetic stimulationand its uses and efficacy inschizophrenia. Multiple sources wereexamined on transcranial magneticstimulation efficacy in relievingpositive and negative symptoms ofschizophrenia. Literature review wasconducted via Ovid Medline andPubMed databases. We foundmultiple published studies and meta-analyses that give evidence thatrepetitive transcranial magneticstimulation can have benefit inrelieving positive and negativesymptoms of schizophrenia,particularly auditory hallucinations.These findings should encourage thepsychiatric community to expandresearch into other applications forwhich transcranial magneticstimulation may be used to treatpatients with psychiatric disability.

INTRODUCTIONSchizophrenia is arguably the

most debilitating of psychiatricillnesses, psychologically, socially,and financially.1 Starting in lateadolescence to early adulthood and

with a lifelong course that typicallyis characterized by relapses, theimpact of schizophrenia on theindividual who suffers from it is bothpervasive and prolonged. Symptomsof schizophrenia are grouped inseveral ways, one of which is todivide them into positive or negativesymptoms. Positive symptoms ofschizophrenia include hallucinations,delusions, disorganized speech, andgrossly disorganized or catatonicbehavior, while the negativesymptoms include affectiveflattening, alogia, anhedonia, andavolition.2.

Pharmacotherapy withantipsychotic medication remainsthe mainstay in the acute andmaintenance treatment ofschizophrenia. Antipsychotic agents(first, second, and third generations)have been shown to be mosteffective in reducing the positivesymptoms of schizophrenia, butunsatisfactory in reducing negativesymptoms and the propensity torelapse.3 Furthermore, almost one-third of patients with positivepsychotic schizophrenia do notrespond to antipsychotic

by JONATHAN C. COLE, DO; CAROLYN GREEN BERNACKI, DO;AMANDA HELMER, RN; NARSIMHA PINNINTI, MD; and JOHN P. O’REARDON, MDAll from the Rowan School of Osteopathic Medicine, Stratford, New Jersey

Innov Clin Neurosci. 2015;12(7–8):12–19

FUNDING: No funding was received for thepreparation of this manuscript.

FINANCIAL DISCLOSURES: The authors haveno conflicts of interest relevant to thecontent of this article.

ADDRESS CORRESPONDENCE TO: JonathanC. Cole, DO, Rowan University-School ofOsteopathic Medicine, The University Doctors2250 Chapel Avenue, Suite 100, Cherry Hill,NJ 08002; Phone: (856) 482-9000 Fax: (856)482-1159; Email: colejo@rowan.edu

KEY WORDS: Transcranial magneticstimulation, schizophrenia, review of literature

[ R E V I E W ]

Efficacy of TranscranialMagnetic Stimulation(TMS) in the Treatment ofSchizophrenia: A Reviewof the Literature to Date

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medication.4 Medicationnonadherence is also a significantissue in the treatment ofschizophrenia, with nonadherencerates of over 70 percent during thecourse of one year.5 There is also asignificant side effect burden withantipsychotic medications, includingextrapyramidal symptoms, weightgain, and metabolic abnormalities,which may make antipsychoticmedications less acceptable topatients and their families.

Due to the limitations ofantipsychotic pharmacologicalagents, we are in need of alternatemodalities for treating schizophreniaor augmenting the antipsychoticmedications currently employed.Neuromodulation is a new frontier inthe investigation of effectivetreatment options for schizophrenia.Among the different methods ofneuromodulation, transcranialmagnetic stimulation (TMS) is onethat has been investigated the mostthoroughly in randomized, controlledtrials over the past 15 years. Thepurpose of this article is to reviewthe literature with regard to theefficacy and safety of TMS on thetreatment of positive and negativesymptoms in schizophrenia.

TMS BACKGROUNDTMS is a noninvasive

neurostimulation technique thatuses alternating magnetic fields toinduce electrical current in thecortex of the brain. In 2008, a TMSdevice from Neuronetics (Malvern,Pennsylvania) was the first to beapproved by the United States Foodand Drug Administration (FDA) forits use in the treatment of patientswho have had a major depressiveepisode and who failed to respond toa single adequate antidepressanttrial. The device was approved usingthe following stimulationparameters: 120-percent motorthreshold, 10Hz, 4 seconds on, 26seconds off. In 2014, the FDAexpanded its approval of this deviceto include treatment of adultpatients with MDD who have failedto benefit from any number of

antidepressant medications. In 2013,a TMS device from Brainsway(Jerusalem, Israel) was approved bythe FDA, also for its use in thetreatment of adult patients withMDD who have failed to benefit fromany number of antidepressantmedications. TMS is considered safeand well tolerated.6

The use of alternating magneticfields to induce electrical current inthe brain is based on Faraday’sprinciple. During application of TMS,an electromagnetic coil is placed onthe scalp that transforms electricalactivity to pulsed magnetic energy,which passes through the craniumunimpeded to induce an electricalfield in the cortex. As a result,neurons depolarize and generateaction potentials.7

If the frequency of the pulse islow (i.e., 1Hz or less), TMS has aninhibitory effect on neural circuits(through GABAnergic [gamma-aminobutyric acid-ergic] effects orlong-term neuronal depression[LTD]).8 Conversely, if the pulsefrequency is high (i.e., greater than1Hz), an excitatory effect will begenerated (through glutamergiceffects or long term potentiation[LTP]). Pulses can be administered assingle, paired, or in a series, called atrain. TMS delivered in a train istermed repetitive TMS (rTMS).While single and paired pulse TMS areused for neurodiagnostic purposes, itis rTMS that has therapeutic benefitin psychiatric disorders.9

Unlike electroconvulsive therapy,no anesthesia is required whenadministering TMS; patients areawake and alert during treatment andcan leave immediately following theirsession. Adverse reactions caninclude post-treatment mild and self-limited headache, scalp pain at thesite of stimulation, and potentialtransient adverse effects on hearingdue to the clicking sound of themachine, which can be preventedwith the use of earplugs. The mostserious potential adverse effect ofTMS is induction of seizure, which israre, with none reported in the pivotaltrial that led to FDA approval and in

which 10,000 sessions were deliveredwithout seizure induction. Patientsshould be carefully screened fororganic brain disease, personal historyof seizure, or family history ofepilepsy.9

According to a case series byStanford et al2 that examined the useof high frequency prefrontal rTMS fortreatment of negative symptoms ofschizophrenia, negative symptomsappear to be associated withhypoactivity of the dorsolateralprefrontal cortex of the brain, whilepositive symptoms appear to beassociated with hyperactivity in theleft temporo-parietal cortex. Stanfordet al2 also suggest that auditoryhallucinations may be due to aberrantactivation of language perceptionareas (i.e., Wernicke’s area) in theleft temporo-parietal cortex. Studieshave investigated the use of lowfrequency TMS to target positivesymptoms, in theory by decreasingcortical excitability and possiblyinhibiting dopamine release.10,11

Conversely, high frequency TMS cantarget negative symptoms byincreasing cortical excitation andinducing dopamine release.2 Negativesymptoms of schizophrenia may bereduced by the use of high-frequencyTMS to the left dorsolateralprefrontal cortex, while positivesymptoms are reduced by applyinglow-frequency TMS to the lefttemporo-parietal cortex.2,10,11

Based on our literature review,research over the past 15 yearssupports the use of TMS as an safeand efficacious means of treatingpositive and negative symptoms ofschizophrenia, with the most notablebody of evidence supporting thereduction of auditory hallucinations.However, not all of the studies weexamined showed efficacy of TMS,and a number of the studies weexamined had negative results.

METHODOLOGYLiterature review for this article

was conducted via Ovid Medline andPubMed databases. The search wascarried out using the terms TMS,repetitive transcranial magnetic

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stimulation, negative symptoms,positive symptoms, schizophrenia,and neuromodulation for the years1996 to November 2013. Searcheswere conducted for original papers,reviews, and meta-analyses. A handsearch for relevant publications wasconducted using references ofarticles reviewed. Articles includedin our analysis were randomized,controlled trials and meta-analyses,while individual case reports, caseseries, and opinion pieces wereexcluded. Our searches yielded atotal of 45 papers. Of these, 31 wereconsidered relevant, and all of thesestudies were included in ouranalysis. Articles that were notpublished in English were excluded.

RESULTSTMS for positive symptoms.

Clinical studies. In 2000, Hoffmanet al12 conducted a double-blindcrossover study of 12 patients withschizophrenia. Patients received 1HzTMS at 80 percent of the motorthreshold over the left temporo-parietal cortex for 15 to 30 minutes.All of these patients remained ontheir antipsychotic medications, andtheir auditory hallucinations wereassessed using the Positive andNegative Syndrome scale (PANSS).13

Reductions in hallucination severitywere found to be significant afteractive treatment as opposed tosham. Interestingly, it was notedthat in patients on anticonvulsantmedications, treatment effects werereduced. This could indicate theneed for higher stimulus dose or areduction or omission ofanticonvulsants. Also the dosinghere was infra-motor threshold,making it unlikely that the trialwould be positive.12

Hoffman et al extended their datafurther in 2003 with a double-blind,crossover trial14 of 24 patients whoreceived 1Hz TMS over the lefttemporo-parietal cortex at 90percent motor threshold for 8 to 16minutes over seven days while beingmaintained on their currentpsychotropic medications. Divergingfrom previous protocol, auditory

hallucinations were assessed usingthe Hallucination Change Scale14 asthe primary measure. Seventy-fivepercent of the patientsdemonstrated a positive responsefollowing the active phase of TMScompared to 17 percent in the shamphase. Patients also carried acounter to track hallucinationfrequency, for which the activegroup showed a linear decrease overtime. For more than half of thepatients in this trial, treatmenteffects lasted 15 weeks.14

In 2004, McIntosh et al15

attempted to replicate the results ofthe Hoffman et al14 study. Sixteenpatients received 1Hz TMS over theleft temporo-parietal cortex at 80percent motor threshold for 8 to 16minutes for one week beforecrossing over to sham treatment andvice versa. Auditory hallucinationswere evaluated using PANSS.Interestingly, 11 of these 16 patientshad received clozapine in the past.No significant effect was foundbetween the active treatment andsham groups. However, thispopulation of patients, with knownpast treatment failures, may havebeen particularly resistant totreatment. In addition, the verysmall sample size indicates that thisstudy was underpowered to detect atreatment effect between groups,and its design is subject to carryovereffects.15

In 2005, Poulet et al16 replicatedthe study by McIntosh et al15

supporting the use of TMS to treatauditory hallucinations. This studyinvolved 10 patients with treatment-resistant auditory hallucinations in adouble-blind crossover design. Theactive TMS treatment involved 1HzTMS over the left temporo-parietalcortex with a stimulus of 90 percentof the motor threshold, receiving10,000 stimuli over five days with aone-week washout before one weekof sham treatment. Auditoryhallucinations were assessed usingthe Auditory Hallucination Ratingscale (AHRS),17 which revealed asignificant decrease in scores duringthe active phase as opposed to

sham. There was a meanimprovement in AHRS scores of 56percent in five days. TMS at lowfrequency provided significantbenefit in reducing auditoryhallucinations. The dose (i.e., pulsesdelivered) of TMS was higher than inprevious trials. These findings wereconsistent with the Hoffman et al14

study in 2003. Similar to Hoffman’sfindings, it was also noted thatpatients on anticonvulsantmedications did not respond as wellto treatment.16

Between 2005 and 2007, aplethora of studies was published inthe area of TMS treatment forauditory hallucinations.18–23 Chibbaroet al18 reported a significant long-term reduction in auditoryhallucinations in 16 patients withschizophrenia. These patients weretaking atypical antipsychotics andwere treated with TMS, with areturn to baseline in their shamgroup. In 2005, Lee et al19 reportedthat both left- and right-sided TMSapplied at low frequencysignificantly reduced auditoryhallucinations in a group of 39patients with schizophrenia andtreatment-refractory auditoryhallucinations. Brunelin et al20

reported significant reduction inauditory hallucinations in 24 right-handed, treatment-refractorypatients with schizophrenia whowere treated with TMS. Thesepatients were randomly selected intosham or active treatment groups forrTMS to the left temporoparietalcortex. In 2006, Jandl et al21

conducted a randomized, crossover,sham-controlled trial of TMS overthe left and right temporo-parietalcortex in 16 patients with auditoryhallucinations but not necessarilyschizophrenia. Five patients whoonly received treatment of the lefthemisphere responded. Group meanhallucination scores did not differacross treatment conditions. Bagatiet al22 conducted a study in 2009that included 40 patients withschizophrenia who were randomizedto either an experimental group or acontrol group. Both groups were

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treated with standard antipsychoticsfollowing a 10-day experimentalphase in which the experimentalgroup received low frequency TMSover the left temporo-parietalcortex. Auditory hallucinations weresignificantly reduced in theexperimental group of patients.Vercammen et al23 reportedsignificant reduction in hallucinationfrequency in patients withschizophrenia who received TMS tothe left temporo-parietal region, aswell as a reduction in self-reportedaffective responsiveness in patientswho received TMS to bilateraltemporoparietal regions.

There have also been a number ofnegative studies on the use of TMSin patients with schizophrenia.24–28

Fitzgerald et al24 did not find adifference in therapeutic effect indomains such as frequency,duration, location, intensity, anddisruption of voices between theactive and sham groups of 20patients with either schizophrenia orschizoaffective disorder whosuffered from moderate to severetreatment-resistant negativesymptoms. However, they did reporta significant reduction in theloudness of hallucinations. In 2006,Saba et al25 treated 18 patients withschizophrenia and refractoryauditory hallucinations with TMS for10 days. TMS was applied over theleft temporoparietal cortex with astimulus of only 80-percent motorthreshold. The authors reported nosignificant differences between theactive and sham groups. Rosa et al26

reported safe administration of TMSconcurrently with clozapine in 11patients with schizophrenia but didnot reveal significant reduction inauditory hallucinations. A largerandomized trial27 in 2011 using fMRIto guide TMS treatment site failed toproduce positive results in reducingseverity of auditory hallucinations.This study involved 63 patients whospecifically suffered from treatment-resistant auditory/visualhallucinations. In 2011, a study byDeJesus et al28 was done using TMSon 17 patients with refractory

schizophrenia who suffered fromauditory hallucinations and werebeing treated with clozapine. Theauthors reported no significantreduction in auditory hallucinationsusing TMS.

In total, we found sixteencontrolled studies and two open-labelstudies using low frequency TMS.12–32

Of the randomized, controlledstudies, 10 studies involving a totalof 257 subjects with psychosisrevealed positive results in treatingauditory hallucinations with TMS,while eight studies involving a totalof 284 subjects with psychosis didnot show any efficacy using TMS.

Meta-analyses. A meta-analysisdone by Aleman et al29 in 2007analyzed data from 10 sham-controlled trials of low frequencyTMS applied to treat auditoryhallucinations in schizophrenia. Pre-versus post-treatment meanstandardized effect size was reported0.76, supporting a robust efficacy ofthis modality in reducing the severityof auditory hallucinations. A secondmeta-analysis on the same topic wasdone in 2009 by Freitas et al,30 whichfurther bolstered the evidence insupport of using TMS to treatauditory hallucinations inschizophrenia. Pre- versus post-treatment effect within the two armsof treatment was 1.28. Similar toAleman’s findings, the effect size forsham-controlled studies was 1.04(large treatment effect). Bothanalyses29,30 provide evidence for asignificant and robust effect onauditory hallucinations in patientswith schizophrenia. TMS was used tostimulate the left temporo-parietalcortex at low frequencies. However,as we indicated above, when thebroader literature base is taken intoconsideration, a total of 10 studiesyielded positive results whereas eightdid not.

A systematic review done bySoltema31 in 2013 compared 25randomized, control trials using theseverity of the hallucinations orpsychosis as the primary outcomemeasure. No differences were seenwith the severity of psychosis. The

severity of hallucinations wassignificantly reduced with paradigmof left temporoparietal TMS at 1hz.Other paradigms were measured, andwere unable to make a difference inhallucination severity.

A review of controlled anduncontrolled studies in the treatmentof auditory hallucinations using lowfrequency TMS to the left temporo-parietal cortex supports thehypothesis that TMS can reducethese symptoms.12–32 Results varyacross studies and this could beattributed to the heterogeneity ofstudy methodology. There is someindication that the dose of TMS hassome bearing on the efficacy. Oneout of three reviewed studies thatused a dose of 80 percent of motorthreshold showed positive results(33%) in reducing auditoryhallucinations, while seven out of 12reviewed studies that used 90percent of MT dose (58%) and bothof two reviewed studies (100%) thatused a dose of 100 percent or morethan motor threshold showedpositive results in reducing auditoryhallucinations. However, more dataare necessary to understand therelationship between the dose ofTMS and efficacy in treating auditoryhallucinations. In addition, the otherfactors that are likely to impact theefficacy of TMS include treatment-resistant symptoms, use ofassociated medication, such asanticonvulsants. As TMS is a welltolerated treatment with no majorcomplications or neurocognitiveimpairment, it is potentially anattractive treatment modality fortreatment-resistant auditoryhallucinations.

Table 1 lists the reviewedliterature on use of TMS fortreatment of auditory hallucinationsin schizophrenia.

TMS for negative symptoms.Clinical studies. The treatment ofnegative symptoms of schizophreniawith high frequency TMS has shownsignificant results overall. Tenrandomized, controlled trials arepublished in the literature (n=228subjects), five of which have

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detected positive results inimproving negative symptoms ofschizophrenia.32–42

The very first study of TMS fornegative symptoms was carried outin 2000 by Rollnik et al.32 In a double-blind, crossover study, 12 patientswith schizophrenia were treated withtwo weeks of daily left prefrontalTMS versus two weeks of shamstimulation, yielding a significantdecrease in the Brief PsychiatricRating scale (BPRS)33 with activeTMS. Another study by Hajak et al in200434 conducted a sham-controlledstudy of 20 patients with

schizophrenia who received highfrequency TMS over 10 days to theleft dorsolateral prefrontal cortex. Atthe end of the study, functionalneuroimaging was performed. Therewas a significant reduction innegative symptoms and depressivesymptoms, while positive symptomsseemed to worsen. However, nochanges were noted on theneuroimaging. Goyal et al35 showedimprovement of negative symptomsin their double-blind, sham-controlled study of 10 right-handedpatients diagnosed withschizophrenia. Prikryl et al36 also

found improvement in negativesymptoms in their randomized,sham-controlled study of 22 patientswith schizophrenia who hadprominent negative symptoms andwere stabilized on antipsychoticmedication. Schneider et al37 used10Hz TMS at 110 percent of themotor threshold over the leftdorsolateral prefrontal cortex in 51patients with schizophrenia, whichshowed significant benefit inreducing negative symptoms as wellas neurocognitive deficits. Cordes etal38 found mild to moderate benefitusing 10Hz stimulation at 110-

TABLE 1. TMS treatment for auditory hallucinations in schizophrenia

AUTHOR/DATE N LOCATION % MT HERTZ TOTAL # OFPULSES RESULTS OF STUDY COIL TYPE

Hoffman/2003 24 L T-P 90 1 unknown 52% of patients had improvementfor at least 15 weeks

Figure ofEight

McIntosh/2004 16 L T-P 80 1 unknown No difference between real andsham treatments

Figure ofEight

Poulet/2005 10 L T-P 90 1 10,000 AHRS improvement significantlymore for active group

Figure ofEight

Chibbaro/2005 16 L T-P 90 1 3,600 SAPS showed significantimprovement in active group

Figure ofeight

Lee/2005 39 L&R T-P 100 1 12,000 Both R and L treatments yieldedbetter CGI scores

Figure ofEight

Brunelin/2006 24 L T-P 90 1 10,000 Significant improvement in AHRScompared to Sham

Figure ofEight

Jandl/2006 16 L&R T-P 100 1 4,500 PSYRATS; mean hallucinationscores did not differ group to group

Figure ofEight

Bagati/2009 40 L T-P 90 1 unknown Significant reduction in AHRSscores for active group

Figure ofEight

Vercammen/2009 38 R&L T-P 90 1 14,400 AH significantly reduced in L T-P

onlyFigure ofEight

Saba/2006 18 L T-P 80 1 3,000 No group differences found Figure ofEight

Rosa/2007 11 L T-P 90 1 9,600 No group differences found Figure ofEight

Slotema/2011 62 L T-P 90 1 18,000 No group differences found Figure ofEight

Abbreviations: MT: motor threshold; ND: no data; AHRS: Auditory Hallucination Rating Scale; PANSS: Positive and Negative Syndrome Scale;PSYRATS: Psychotic Symptoms Rating Scale; AH: auditory hallucinations; SAPS-NS: Scale for the Assessment of Positive Symptoms-Negative Symptoms; L T-P: left temporo-parietal cortex; L&R T-P: left and right temporo-parietal cortex; L or R T-P: left or right temporo-parietal cortex

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percent motor threshold in a sham-controlled trial of 35 individuals withchronic schizophrenia.

In a group of 22 chronic,hospitalized patients withschizophrenia, high frequency TMSwas not found to have a therapeuticeffect.39 Novak et al40 in 2006 wereunable to show that high frequencyTMS over the left dorsolateralprefrontal cortex would reducenegative symptoms in 16 patientswith schizophrenia who hadpredominant negative symptoms andwere stabilized on antipsychoticmedication. This study only used 90-percent motor threshold with a totalof 2000 stimuli per session. AlthoughMogg et al41 did not see improvementin negative symptoms, they did seesome improvement in cognitivefunction in their study of 17 right-

handed patients with schizophreniawho were treated with TMS. In atwo-armed, double-blind,randomized, controlled trial,Fitzgerald et al24 investigated theefficacy of bilateral high frequencyTMS to treat moderate-to-severe,treatment-resistant negativesymptoms in 20 patients withschizophrenia or schizoaffectivedisorder. The authors found nosubstantial benefit. This study usedbilateral high frequency TMS ascompared to many trials where TMSis used unilaterally. Also, this studyhad a three-week treatment period,which may be too short of a coursefor longstanding negative symptomsof schizophrenia.

Meta-analyses. Opinions vary asto the effectiveness of highfrequency TMS in treating negative

symptoms of schizophrenia. A meta-analysis completed in 2009 thatincluded eight studies of highfrequency (10Hz) stimulus applied tothe left dorsolateral prefrontal cortexin patients with schizophreniashowed an effect size of 0.58.30 Whenthree open-label trials were excludedfrom analysis, the effect size for thecontrolled studies dropped to 0.27.This was appropriately interpretedby the authors as a marginal effect. Asecond meta-analysis examinedseven controlled studies of highfrequency to the left dorsolateralprefrontal cortex in patients withschizophrenia and reported an effectsize of 0.63.42 As effect sizes forantipsychotic medication treatmentof negative symptoms range from0.17 to 0.21, those of TMS rangingfrom 0.27 to 0.63 are encouraging.

TABLE 2. TMS treatment for negative symptoms in schizophrenia

AUTHOR/DATE N LOCATION % MT HERTZ # OFPULSES RESULTS OF STUDY COIL TYPE

Rollnick/2000 12 Left DLPFC 80 20 8000 Positive BPRS ratings for active vs.sham subjects

Figure ofEight

Hajak/2004 20 Left DLPFC 110 10 10,000 CDSS showed improvement ofnegative symptoms

Figure ofEight

Goyal/2007 10 Left DLPFC 110 10 10,000 CDSS showed improvement in activegroup

Figure ofEight

Prikryl/2008 22 Left DLPFC 110 10 22500 25% reduction in PANSS in activegroup

Figure ofEight

Schneider/2008 17 Left DLPFC 110 10 20000 SANS score showed marked

reduction in active groupFigure ofEight

Cordes/2010 35 Left DLPFC 110 10 10000 Only a subgroup of patients showedmild improvement in GAF

Figure ofEight

Holi/2004 22 Left DLPFC 100 10 10000 NO PANSS difference found betweengroups

Figure ofEight

Novak/2006 16 Left DLPFC 90 20 20000 NO PANSS difference found betweengroups

Figure ofEight

Fitzgerald/2008 20 BL DLPFC 110 10 15000 SANS did not show improvement in

treated groupFigure ofEight

MT: motor threshold; PANSS: Positive and Negative Syndrome Scale; SANS: Scale for the Assessment of Negative Symptoms; SAPS: Scalefor the Assessment of Positive Symptoms; MADRS: Montgomery-Asberg Depression Rating Scale; CDSS: Calgary Depression Scale forSchizophrenia; L DLPFC: left dorso-lateral prefrontal cortex; R&L PFC: right and left prefrontal cortex

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Table 2 lists the reviewedliterature on use of TMS fortreatment of negative symptoms ofschizophrenia.

SAFETY OF TMSIn 2007, in a multicenter study,

researchers looked at safety andefficacy of TMS in the treatment ofmajor depression.1 Of the 301subjects in th study, the onlyadverse event attributed to TMS at arate higher than placebo/sham wasscalp discomfort (occurring in 38.5%of subjects for a 1-week period atthe start of the TMS course). Noseizures occurred.1

SUMMARYBased on our examination of the

literature from the past 15 years, weconclude that the use of TMS inschizophrenia has its greatestefficacy in treating auditoryhallucinations. The frequency andseverity of auditory hallucinations, inparticular, may be decreased bytargeting low frequency TMS stimulito Wernicke’s area in the lefttemporo-parietal cortex. Since 20percent of patients withschizophrenia experience treatment-resistant auditory hallucinations,13

further studies to assess the efficacyof TMS in both inpatient andoutpatient populations are merited.

Based on our examination of theliterature, reduction of negativesymptoms using high frequency TMSto the dorso-lateral prefrontal cortexis encouraging given our currentlack of treatment options for thesedebilitating symptoms. Positiveresults in reducing cognitivesymptoms in schizophrenia are alsopromising and warrant further studyof the efficacy of TMS on cognitivesymptoms of schizophrenia.

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