BlueCross and BlueShield of Montana Medical Policy/Codes
Transcranial Magnetic Stimulation as a Treatment of Depression and Other Psychiatric/Neurologic Disorders
Chapter: Medicine: Treatments
Current Effective Date: September 24, 2013
Original Effective Date: January 13, 2012
Publish Date: September 24, 2013
Revised Dates: March 22, 2102; July 29, 2013
Description

Background

Transcranial magnetic stimulation (TMS) is a non-invasive method of delivering electrical stimulation to the brain. A magnetic field is delivered through the skull, where it induces electric currents that affect neuronal function. Repetitive TMS (rTMS) is being evaluated as a treatment of depression and other psychiatric or neurologic brain disorders.

TMS was first introduced in 1985 as a new method of noninvasive stimulation of the brain. The technique involves placement of a small coil over the scalp; a rapidly alternating current is passed through the coil wire, producing a magnetic field that passes unimpeded through the scalp and bone, resulting in electrical stimulation of the cortex. TMS was initially used to investigate nerve conduction; for example, TMS over the motor cortex will produce a contralateral muscular-evoked potential. The motor threshold, which is the minimum intensity of stimulation required to induce a motor response, is empirically determined for each individual by localizing the site on the scalp for optimal stimulation of a hand muscle, then gradually increasing the intensity of stimulation. The stimulation site for treatment is usually 5 cm anterior to the motor stimulation site.

Interest in the use of TMS as a treatment for depression was augmented by the development of a device that could deliver rapid, repetitive stimulation Imaging studies had shown a decrease in activity of the left dorsolateral prefrontal cortex (DLPFC) in depressed patients, and early studies suggested that high frequency (e.g., 5–10 Hz) TMS of the left DLPFC had antidepressant effects. Low frequency (1–2 Hz) stimulation of the right DLPFC has also been investigated. The rationale for low frequency TMS is inhibition of right frontal cortical activity to correct the interhemispheric imbalance. A combination approach (bilateral stimulation) is also being explored. TMS is also being tested as a treatment for other disorders including schizophrenia, migraine, spinal cord injury, tinnitus, and fibromyalgia. In contrast to electroconvulsive therapy (ECT), TMS does not require anesthesia and does not induce a convulsion

Maximizing surgical removal of brain tumors while minimizing neurologic deficits is challenging. At present, the gold standard for identifying critical motor areas in brain tumor surgery is intraoperative invasive direct current stimulation (DCS) through a handpiece. (40) Navigated transcranial magnetic stimulation (nTMS) can be used to map functionally essential motor areas preoperatively. (37)  nTMS can be a tool for targeted, noninvasive stimulation of the cerebral cortex. The clinical relevance of nTMS is not fully known because localizing the optimal stimulation site and determining the optimal stimulation strength have been dependent on time-consuming experimentation and skill. Moreover, in many disorders, it has been uncertain whether the lack of motor responses is the result of true pathophysiological changes or merely because of unoptimal stimulation. (38)

Regulatory Status

Devices for transcranial stimulation have received clearance by the U.S. Food and Drug Administration (FDA) for diagnostic uses. One device, NeoPulse (Neuronetics, Atlanta, GA), received approval in Canada, Israel and the U.S. as a therapy for depression  Initially examined by the FDA under a 510(k) application, the NeoPulse, now known as NeuroStar® TMS, received clearance for marketing as a “De Novo” device in 2008.  NeuroStar TMS is indicated for the treatment of patients with depression who have failed one six-week course of antidepressant medication. In 2011, the NBS System 4® (Nextstim) received 510k clearance; the NBS System 4 can be used to locate areas of the brain that are capable of evoking muscle responses when stimulated.(FDA). (41)

Note: An FDA advisory panel met in January 2007 to determine if the risk-to-benefit profile for the NeoPulse was comparable to the risk-to-benefit profile of predicate ECT devices. The panel was not asked for a recommendation regarding the regulatory determination of substantial equivalence for this 510(k) submission. Materials presented at the Neurological Devices Panel meeting as well as a summary are posted at www.fda.gov .

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Investigational

Blue Cross Blue Shield of Montana (BCBSMT) considers transcranial magnetic stimulation (TMS) experimental, investigational and unproven as a treatment of depression and other psychiatric or neurologic disorders including, but not limited to, schizophrenia or migraine headaches.

Navigated transcranial magnetic stimulation (nTMS) is considered experimental, investigational and unproven.

Rationale

The Blue Cross and Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) published an assessment of repetitive TMS (rTMS) for depression in 2009. The TEC Assessment concluded that the available evidence did not permit conclusions regarding the effect of TMS on health outcomes. Limitations of the evidence included:

  • Equivocal efficacy in the largest sham-controlled trial of TMS,
  • Uncertain clinical significance of the short-term anti-depressant effects found in meta-analyses,
  • A lack of information beyond the acute period of treatment, and
  • Lack of comparison with standard therapy (a second course of antidepressant therapy) in the population for whom TMS is indicated (patients who have failed one 6-week course of antidepressant medication).

BCBSA published an updated TEC Assessment of TMS for depression in 2011. Included were six recent meta-analyses, the largest of which evaluated 30 double-blind sham-controlled trials with a total of 1,383 patients. Recent clinical trials were also reviewed. The 2011 TEC Assessment reached the following conclusions:

  • The meta-analyses and recent clinical trials of TMS generally show statistically significant effects on depression outcomes at the end of the TMS treatment period. However, the clinical significance and durability of the effect are not well-characterized.
  • The largest randomized clinical trial showed a greater effect in patients with only one prior treatment failure, with possibly minimal or no effect in patients with greater than one prior treatment failure. Based on current evidence, it cannot be determined whether TMS after one treatment failure would be as effective as the current standard of a second course of antidepressant therapy.
  • Also identified as gaps in current knowledge are whether TMS is effective as an adjunctive treatment and whether retreatment is effective.

Following is a summary of the key literature to date, focusing on randomized controlled trials (RCTs). Studies published prior to 2008 are included if the study design was a randomized sham-controlled double-blind trial that enrolled at least 40 subjects; refer to the 2008 meta-analysis by Schutter for a summary of study characteristics and stimulation parameters used in these trials. The evidence review is divided by key differences in treatment protocols, specifically high-frequency left dorsolateral prefrontal cortex stimulation (DLPFC), low-frequency (1–2 Hz) stimulation of the right dorsolateral prefrontal cortex, or combined high-frequency and low-frequency stimulation.

Note that over the last decade, there has been a trend to increase the intensity, trains of pulses, total pulses per session, and number of sessions (Gross et al.). Unless otherwise indicated in the trials described below, stimulation was set at 100% to 120% of motor threshold, clinical response was defined as an improvement of 50% or more on the Hamilton Depression Rating Scale (HAM-D), and remission was considered to be a score of 7 or less on the HAM-D.

High Frequency rTMS of the Left Dorsolateral Prefrontal Cortex (DLPFC) for Treatment-Resistant Depression (TRD)

Lam and colleagues conducted a meta-analysis of 24 randomized controlled trials comparing active versus sham rTMS in patients with TRD, although there were varying definitions of TRD. This analysis calculated a number needed to treat of six, with a clinical response in 25% of active rTMS and 9% of sham rTMS patients.  Remission was reported for 17% of active rTMS and 6% of sham rTMS patients.

The largest study (23 study sites) included in the meta-analysis was a double-blind multicenter trial with 325 TRD  patients randomized to daily sessions of high frequency active or sham rTMS (Monday to Friday for six weeks) of the left DLPFC (O’Reardon et al.). TRD was defined as failure of at least one adequate course of antidepressant treatment. Patients had failed an average of 1.6 treatments in the current episode, with about half of the study population failing to benefit from at least two treatments. Loss to follow-up was similar in the two groups, with 301 (92.6%) patients completing at least one post-baseline assessment and an additional 8% of patients from both groups dropping out before the four-week assessment. Intent-to-treat analysis showed a trend favoring the active rTMS group in the primary outcome measure (two points on the Montgomery-Asberg Depression Rating Scale; p = 0.057) and a modest (two-point) but significant improvement over sham treatment on the HAM-D. The authors reported that after six weeks of treatment the subjects in the active rTMS group were more likely to have achieved remission than the sham controls (14% vs. 5%), although this finding is limited by loss to follow-up.

In 2010, George et al. reported a randomized sham-controlled trial that involved 199 patients treated with left-prefrontal rTMS. This was a multi-centered study involving patients with a moderate level of treatment resistance. The response rate using an intention-to-treat analysis was 14% for rTMS and 5% for sham (p=0.02). In this study, the site for stimulation was determined through pre-treatment magnetic resonance imaging (MRI). Results from Phase 2 (open treatment of non-responders) and Phase 3 (maintenance and follow-up) will be reported in the future.

Another randomized sham-controlled double-blind trial was conducted in 68 patients who had failed at least two courses of antidepressants (Avery et al.). Three patients in each group did not complete the 15 treatment sessions or were excluded due to a change in medication during treatment, resulting in 91% follow-up. Independent raters found a clinical response in 31% (11 of 35) of the active rTMS patients and 6% (2 of 33) of the sham group. The average change in HAM-D was 7.8 for the active group and 3.7 for the control group. The Beck Depression Inventory (BDI) decreased by 11.3 points in the active rTMS group and 4.8 points in controls. Remission was observed in seven patients (20%) in the active rTMS group and one patient (3%) in the control group. Regarding effectiveness of blinding, 15% of subjects in each group guessed that they were receiving active TMS after the first session. After the 15th session, 58% of the rTMS group and 43% of the sham group guessed that they had received active TMS; responders were more likely than non-responders (85% vs. 42%) to think that they had received the active treatment. The 11 responders were treated with antidepressant medication and followed up for six months. Of these, one was lost to follow-up, five (45%) relapsed, and five (45%) did not relapse.

Rossini and colleagues randomized 54 patients who had failed at least two adequate courses of antidepressants to sham control or active rTMS at 80% or 100% of motor threshold for 10 sessions over a two-week period. Double-blind evaluation found an intensity-dependent response with 6% (1 of 16) of the sham, 28% (5 of 18) of the 80% MT, and 61% (11 of 18) of the 100% motor threshold groups showing improvement of 50% or more over a five-week evaluation. All of the patients reported that they were unaware of the differences between sham and active stimulation.

In a 2008 report, Mogg et al. randomized 59 patients with major depression who had failed at least one course of pharmacotherapy for the index depressive episode. In this study population, 78% of the patients had failed two treatment courses and 53% had failed three. The sham coil, which was provided by Magstim, was visually identical to the real coil and made the same clicking sound, but did not deliver a magnetic field to scalp or cortex. Blinded assessments were measured two days after the fifth and final (tenth) sessions (97% follow-up), with additional assessments at six weeks (90% follow-up) and four months (83% follow-up). The mean group difference was estimated to be 0.3 points in HAM-D scores for the overall analysis. Interpretation of this finding is limited since seven sham patients (23%) were given a course of real rTMS after the six-week assessment and analyzed as part of the sham group in the intent-to-treat analysis. The study was powered to detect a difference of 3.5 points in the HAM-D between the active and sham groups, and the 2.9-point group difference observed at the end of treatment was not significant. A higher percentage of patients in the active rTMS group achieved remission criteria of ≤8 points on the HAM-D (25% vs.10% control), and there was a trend for more patients to achieve clinical response in the active rTMS group (32% vs.10%, p = 0.06). All of the 12 patients who met the criterion for clinical response (nine active and three sham) thought that they had received real rTMS, with more patients in the active group (70%) than the sham group (38%) guessing that they had received the real treatment. Interpretation of this finding is also limited, since the reason the subjects guessed that they had active treatment was not reported, and the subjects were not asked to guess before they began to show a clinical response.

A small double-blind randomized trial from 2009 suggests that specific targeting of Brodman areas 9 and 46 may enhance the anti-depressant response compared with the standard targeting procedure, i.e., measuring 5 cm anterior from the motor cortex (Fitzgerald et al., 2009, p.1255-62). Fifty-one patients who had failed at least two 6-week courses of antidepressant medication (average 5.7 failed courses) were randomized to a standard localization procedure or to structural MRI-aided localization for three weeks (with one-week extension if >25% reduction on the Montgomery-Asberg Depression Rating (MADRS). Six patients in the targeted group and 10 in the standard group withdrew due to lack of response. A single patient in the targeted group and five in the standard group withdrew for other reasons, resulting in 17 patients in the targeted group and 12 in the standard group continuing for the full four weeks of treatment. To adjust for the imbalance in discontinuation rates, a mixed model statistical analysis was used. There was a significant difference between the groups in the overall mixed model analysis, and planned comparisons showed significant improvement in MADRS scores for the targeted group at four weeks. Response criteria were met by 42% of the targeted group and 18% of the standard group. Remission criteria were met by 30% of the targeted group and 11% of the standard group. Although encouraging, additional trials with a larger number of subjects are needed to evaluate this procedure.

Several studies have compared the outcomes of rTMS with those from ECT. In one study, 40 patients with nonpsychotic major depression were treated over the course of a month (20 total sessions) and evaluated with the HAM-D, in which a response was defined as a 50% decrease with a final score of less than or equal to 10 (Grunhaus et al.). There was no difference in response rate between the two groups; 12 of 20 responded in the ECT group compared to 11 of 20 in the magnetic stimulation group. A United Kingdom National Institute for Health Research health technology assessment compared efficacy and cost effectiveness of rTMS and ECT (McLoughlin et al.). Forty-six patients who had been referred for ECT were randomized to either ECT (average of 6.3 sessions) or a 15-day course (five treatments per week) of rTMS of the left DLPFC. ECT resulted in a 14-point improvement in the HAM-D and a 59% remission rate. rTMS was less effective than ECT (five-point improvement in HAM-D and a 17% remission rate). Another study reported no significant difference between ECT and rTMS in 42 patients with TRD; however, response rates for both groups were low (Rosa et al.). The number of remissions (score of ≤7 on the HAM-D) totaled three (20%) for ECT and two (10%) for rTMS.

Janicak and colleagues reported on assessment of relapse during a multisite, open-label study. In this study, patients who met criteria for partial response during either a sham–controlled or open-label phase of a prior study were tapered from rTMS and simultaneously started on maintenance antidepressant monotherapy. They were then followed for 24 weeks. Ten of 99 patients relapsed. Thirty-eight patients had symptom worsening, and 32 of these (84%) had symptomatic benefit with adjunctive rTMS. Additional data are needed related to durability of effect and to maintenance phases.

Low Frequency rTMS of the Right Dorsolateral Prefrontal Cortex (DLPFC) or Bilateral Stimulation for Treatment-Resistant Depression (TRD)

Fitzgerald et al. (2003) randomized 60 patients who had failed a minimum of at least two 6-week courses of antidepressant medications into 1 of 3 groups; high frequency left rTMS, low frequency right rTMS, or sham stimulation over 10 sessions. All patients who entered the study completed the double-blind randomized phase, which showed no difference between the two active treatments (left: 13.5% reduction; right: 15% reduction) and greater improvements in the MADRS scores compared to the sham group (0.76% reduction). Only one patient achieved 50% improvement during the initial two weeks. Then, only the subjects who showed at least 20% improvement at the end of the 10 sessions (15 active and two sham) continued treatment. Patients who did not respond by at least 20% were switched to a different active treatment. From week 2 to week 4 there was greater improvement in the low frequency right rTMS group compared with the high frequency left rTMS group (39% vs. 14% improvement in MADRS). Seven patients (18% of 40) showed a clinical response of >50% by the end of the four weeks.

In a subsequent study Fitzgerald and colleagues (2006) randomized 50 patients with TRD to sequential bilateral active or sham rTMS. After two weeks of treatment, three subjects had dropped out of the sham treatment group and there was a slight but non-significant improvement favoring the active group for the MADRS (26.2 vs. 30.9) and the BDI (18.3 vs. 21.6). At this time point, 60% of subjects receiving active rTMS and 50% of subjects receiving sham treatment guessed that they were in the active group. The clinical response was reported by subjects as the major reason for their guess, with 11 of 13 responders (nine active and two sham) guessing that they were in the active group. As in the earlier study, only the subjects who showed at least 20% improvement at the end of each week continued treatment. Treatment on week three was continued for 15 subjects in the active group and seven subjects in the sham group. By week six, 11 subjects in the active rTMS remained in the study, with no control subjects remaining. Final ratings for the 11 subjects who continued to respond through week six were 8.9 on the MADRS and 9.2 on the BDI.

Another multicenter double-blind trial randomized 130 patients with TRD to five sessions per week of either 1- or 2-Hz rTMS over the right DLPFC (Fitzgerald et al., 2009, p.655-66). Sixty-eight patients (52%) completed four weeks of treatment; there was an approximate 30% improvement in depression scales, with no differences between the 1- or 2-Hz groups. Due to the potential for placebo effects for this type of intervention, the absence of a sham control group limits interpretation.

A small randomized, sham-controlled trial was published in 2010 that involved either right or left rTMS in 48 patients with TRD (Triggs et al.). Overall reductions in the HAM-D-24 from baseline to three months were not significantly different between rTMS and sham treatment groups. In this small study, right cranial stimulation was significantly more effective than left cranial stimulation (sham or rTMS).

rTMS as an Adjunctive Treatment for Moderate to Severe Depression

Schutter conducted a meta-analysis of 30 double-blind randomized sham-controlled trials (1,164 patients) of high frequency rTMS over the left DLPFC in patients with major depression. The pooled weighted mean effect size for treatment was calculated with Hedges g (a standardized mean difference that adjusts for sampling variance) to be 0.39 (95% confidence interval 0.25–0.54), which is considered moderate. For 27% of the population rTMS was used as a primary/adjunctive treatment; three trials were included that used rTMS as a primary/adjunctive treatment for depression and enrolled more than 40 subjects (Koerselman et al., 2004; Rumi et al., 2005; Herwig et al., 2007). rTMS has also been examined in patients with clinical evidence of cerebrovascular disease and late-life depression (Jorge et al.). Additional research on whether adjunctive rTMS can improve response to pharmacologic treatment as a first-line therapy is also needed.

Schizophrenia

The largest area of TMS research outside of depressive disorders appears to be treatment of auditory hallucinations in schizophrenia resistant to pharmacotherapy. In 2011, BCBSA TEC published an assessment of TMS as an adjunct treatment for schizophrenia. Five meta-analyses were reviewed, along with RCTs in which measurements were carried out beyond the treatment period. A meta-analysis of the effect of TMS on positive symptoms of schizophrenia (hallucinations, delusions, and disorganized speech and behavior) did not find a significant effect of TMS. Four meta-analyses that looked specifically at auditory hallucinations showed a significant effect of TMS. It was noted that outcomes were evaluated at the end of treatment, and the durability of the effect is unknown. The TEC Assessment concluded that the available evidence is insufficient to demonstrate that TMS is effective in the treatment of schizophrenia.

Other Psychiatric/Neurologic Disorders

Two small (n=18 and 30) randomized sham-controlled trials found no evidence of efficacy for treatment of obsessive compulsive disorder (OCD), although another small sham-controlled trial (n=21) reported promising results with bilateral stimulation of the supplementary motor area (Sachdev et al.; Mantovani et al.; Mansur et al.).

In 2011, Short et al. evaluated the efficacy of adjunctive rTMS as a treatment for fibromyalgia pain in a small randomized controlled pilot study. Twenty patients with fibromyalgia, defined by the American College of Rheumatology criteria, were randomized to 10 sessions of left prefrontal rTMS or sham TMS along with their standard medications. At two weeks after treatment, there was a significant change from baseline in average visual analog scale (VAS) for pain in the rTMS group (from 5.60 to 4.41) but not in the sham-treated group (from 5.34 to 5.37). There was also a significant improvement in depression symptoms in the active group compared to baseline (from 21.8 to 14.10) but not in the sham group (from 17.6 to 16.4). There were no statistically significant differences between the groups in this small trial. Additional study with a larger number of subjects is needed.

Ahmed et al. randomized 45 patients with probable Alzheimer’s disease to five sessions of bi-lateral high-frequency rTMS, bi-lateral low-frequency rTMS, or sham TMS over the dorsolateral prefrontal cortex. Thirty-two patients had mild to moderate dementia and 13 had severe dementia. There were no significant differences between groups at baseline. Measures of cortical excitability immediately after the last treatment session showed that treatment with high-frequency rTMS reduced the duration of transcallosal inhibition. At three months after treatment, the high-frequency rTMS group improved significantly more than the other two groups in standard rating scales, and subgroup analysis showed that this was due primarily to improvements in patients with mild/moderate dementia. Patients in the subgroup of mild to moderate dementia who were treated with high-frequency rTMS improved from 18.4 to 22.6 on the Mini Mental State Examination (MMSE), from 20.1 to 24.7 on the Instrumental Daily Living Activity (IADL) scale and from 5.9 to 2.6 on the Geriatric Depression Scale (GDS).

In 2008, Walpoth et al. reported no evidence of efficacy of rTMS in a small trial (n=14) of patients with bulimia nervosa.

Practice Guidelines and Position Statements

The Canadian Network for Mood and Anxiety Treatments (CANMAT) updated their clinical guidelines on neurostimulation therapies for the management of major depressive disorder in adults (Kennedy et al.). The evidence reviewed supported ECT as a first-line treatment under specific circumstances; when used in patients who have failed to respond to one or more adequate antidepressant medication trials, ECT response rates have been estimated to be 50-60%. The guidelines considered rTMS to be a safe and well-tolerated treatment, with no evidence of cognitive impairment. Based on the 2008 meta-analysis by Lam et al., response (25%) and remission (17%) rates were found to be greater than sham but lower than for other interventions for TRD, leading to a recommendation for rTMS as a second line treatment. The guidelines indicated that there is a major gap in the evidence base regarding maintenance rTMS, as only one open-label case series was identified.

The Movement Disorder Society published an evidence-based review of treatments for the non-motor symptoms of Parkinson’s disease in 2011 (Seppi et al.). The review found insufficient evidence to make adequate conclusions on the efficacy rTMS for the treatment of depression in Parkinson’s disease.

In 2010 guidelines, the American Psychiatric Association stated that data are insufficient to recommend rTMS as initial therapy in major depressive disorder; for patients with inadequate response to pharmacotherapy, ECT remains the most effective form of therapy and should be considered, but TMS may be an option.

In 2007 guidelines, the National Institute for Health and Clinical Excellence stated that, due to lack of sufficient data regarding clinical efficacy, rTMS should be utilized in research studies only to provide further analysis of factors such as treatment duration and frequency and intensity of application; no major safety concerns have been identified with the use of TMS in severe depression.

Summary

Evidence on rTMS for depression and other psychiatric and/or neurologic disorders is insufficient to permit conclusions regarding the effect of this technology on health outcomes. The literature on rTMS for treatment-resistant depression is the most developed and includes a number of double-blind randomized sham-controlled short-term trials. Results of these trials show mean improvements of uncertain clinical significance across groups as a whole. The percentage of subjects who show a clinically significant response is reported at approximately 2-3 times that of sham controls, with approximately 15% to 25% of patients meeting the definition of clinical response (Mantovani et al.).

The treatment protocols are time intensive, and the patients who are most likely to benefit from treatment are not currently known. Importantly, a number of open issues need to be addressed before this procedure is widely implemented. The available studies do not establish that rTMS is as good as available alternatives, as the vast majority of the trials do not compare rTMS to alternative active treatments. Alternative treatments include a variety of different medication regimens and psychological talk therapy, both of which have demonstrated efficacy. In addition, further research is needed to determine which of the locations and treatment parameters examined to date are most effective to guide the number of sessions needed to elicit a clinically significant response, to determine whether the response is durable with or without anti-depressant medications, and to provide some information about whether maintenance treatments are needed, and which types of maintenance treatment are most effective..

A search for transcranial magnetic stimulation on the online site ClinicalTrials.gov indicates that these issues are being actively investigated. Given the number of important questions that remain for this novel treatment approach, the current state of knowledge is not sufficient to expand utilization outside of the research setting. Therefore, rTMS is considered experimental, investigational and unproven for the treatment of depression and other psychiatric and/or neurologic disorders.

2012 Update

A search of published literature about navigated transcranial magnetic stimulation (nTMS) located only small case series and reviews of records. No random controlled trials were located.

Picht et al. (37) conducted an assessment of the influence of nTMS on surgical planning for tumors in or near the motor cortex, to evaluate how much influence, benefit, and impact nTMS has on the surgical planning for tumors near the motor cortex. This study reviewed the records of 73 patients with brain tumors in or near the motor cortex, mapped preoperatively with nTMS. The surgical team prospectively classified how much influence the nTMS results had on the surgical planning. Stepwise regression analysis was used to explore which factors predict the amount of influence, benefit, and impact nTMS has on the surgical planning. The influence of nTMS on the surgical planning was as follows: it confirmed the expected anatomy in 22% of patients, added knowledge that was not used in 23%, added awareness of high-risk areas in 27%, modified the approach in 16%, changed the planned extent of resection in 8%, and changed the surgical indication in 3%. The study concluded that nTMS had an objective benefit on the surgical planning in one fourth of the patients and a subjective benefit in an additional half of the patients. It had an impact on the surgery itself in just more than half of the patients. By mapping the spatial relationship between the tumor and functional motor cortex, nTMS improves surgical planning for tumors in or near the motor cortex.

Saisanen et al. (38) conducted a study that characterized the muscle responses from human primary motor cortex system by navigated TMS to provide normative values for the clinically relevant TMS parameters on 65 healthy volunteers aged 22 to 81 years. They delivered focal TMS pulses on the primary motor area, and recorded muscle responses on thenar and anterior tibial muscles. Motor threshold, latencies and amplitudes of motor-evoked potentials, and silent period duration were measured. The correction of the motor-evoked potential latency for subjects' height was provided. The authors concluded that they provided a modified baseline of TMS-related parameters for healthy subjects, and stated that earlier such large-scale baseline material has not been available.

Vajkoczy et al (39) conducted a comparative evaluation of navigated brain stimulation and direct electrocortical stimulation in the first 30 patients presenting with rolandic tumor. Their objective was evaluation of the concordance between results of non-invasive mapping with the NBS System (Nexstim Oy, Finland) and direct electrocortical stimulation (DCS), and evaluation of clinical utility of NBS mapping data through changed or improved surgical strategy. This was a series of 30 patients for whom the authors found preoperative mapping of the motor cortex with NBS to be as accurate as direct cortical stimulation (DCS). NBS mapping has the potential to be of higher clinical utility for preoperative motor mapping than functional magnetic resonance imaging (fMRI).

The US National Institutes of Health has a trial underway on nTMS in monitoring stroke recovery (NCT01005394). The purposes of this research study are to: 1) determine changes in brain activity during the first 6 months after stroke (to determine how the brain "re-wires"); 2) compare changes in recovery of motor function with changes in brain re-wiring; 3) determine the ability of TMS to "predict" functional outcome in the first 6 months after stroke. The primary hypotheses are: 1) functional recovery will be correlated with TMS changes (as measure motor threshold (MT), motor evoked potentials (MEPs) and recruitment curves; 2) baseline TMS will predict future functional outcomes at 3 and 6 months. This trial is currently recruiting participants. (40)

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

Experimental, investigational and unproven for all diagnoses.

ICD-10 Codes

Experimental, investigational and unproven for all diagnoses.

Procedural Codes: 90867, 90868, 90869, 0310T
References
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  2. Grunhaus L, Schreiber S, Dolberg OT et al.  A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression.  Biol Psychiatry 2003; 53(4):324-31.
  3. Koerselman F, Laman DM, van Duijn H et al.  A 3-month follow-up, randomized, placebo-controlled study of repetitive transcranial magnetic stimulation in depression.  J Clin Psychiatry 2004; 65(10):1323-9.
  4. Rossini D, Lucca A, Zanardi R et al.  Transcranial magnetic stimulation in treatment-resistant depressed patients: a double-blind, placebo-controlled trial.  Psychiatry Res 2005; 137(1-2):1-10.
  5. Rumi DO, Gattaz WF, Rigonatti SP et al.  Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study.  Biol Psychiatry 2005; 57(2):162-6.
  6. Avery DH, Holtzheimer PE 3rd, Fawaz W et al.  A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression.  Biol Psychiatry 2006; 59(2):187-94.
  7. Fitzgerald PB, Benitez J, de Castella A et al.  A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression.  Am J Psychiatry 2006; 163(1):88-94.
  8. Rosa MA, Gattaz WF, Pascual-Leone A et al.  Comparison of repetitive transcranial magnetic stimulation and electroconvulsive therapy in unipolar non-psychotic refractory depression: a randomized, single-blind study.  Int J Neuropsychopharmacol 2006; 9(6):667-76.
  9. Fitzgerald PB, Huntsman S, Gunewardene R et al.  A randomized trial of low-frequency right-prefrontal-cortex transcranial magnetic stimulation as augmentation in treatment-resistant major depression.  Int J Neuropsychopharmacol 2006; 9(6):655-66.
  10. McLoughlin DM, Mogg A, Eranti S et al.  The clinical effectiveness and cost of repetitive transcranial magnetic stimulation versus electroconvulsive therapy in severe depression: a multicentre pragmatic randomised controlled trial and economic analysis.  Health Technol Assess 2007; 11(24):1-54.
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  12. Biol Psychiatry 2007; 62(11):1208-16.
  13. Herwig U, Fallgatter AJ, Höppner J et al.  Antidepressant effects of augmentative transcranial magnetic stimulation: randomised multicentre trial.  Br J Psychiatry 2007; 191:441-8.
  14. Sachdev PS, Loo CK, Mitchell PB et al.  Repetitive transcranial magnetic stimulation for the treatment of obsessive compulsive disorder: a double-blind controlled investigation.  Psychol Med 2007; 37(11):1645-9.
  15. Gross M, Nakamura L, Pascual-Leone A et al.  Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies.  Acta Psychiatr Scand 2007; 116(3):165-73.
  16. Lam RW, Chan P, Wilkins-Ho M et al.  Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and metaanalysis.  Can J Psychiatry 2008; 53(9):621-31.
  17. Jorge RE, Moser DJ, Acion L et al.  Treatment of vascular depression using repetitive transcranial magnetic stimulation.  Arch Gen Psychiatry 2008; 65(3):268-76.
  18. Walpoth M, Hoertnagl C, Mangweth-Matzek B et al.  Repetitive transcranial magnetic stimulation in bulimia nervosa: preliminary results of a single-centre, randomised, double-blind, sham-controlled trial in female outpatients.  Psychother Psychosom 2008; 77(1):57-60.
  19. Mogg A, Pluck G, Eranti SV et al.  A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression.  Psychol Med 2008; 38(3):323-33.
  20. Schutter DJ.  Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a meta-analysis.  Psychol Med 2009; 39(1):65-75.
  21. Fitzgerald PB, Hoy K, McQueen S et al.  A randomized trial of rTMS targeted with MRI based neuro-navigation in treatment-resistant depression.  Neuropsychopharmacology 2009; 4(5):1255-62
  22. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC).  Transcranial magnetic stimulation for depression.  TEC Assessments 2009; Volume 24, Tab 5.
  23. Kennedy SH, Milev R, Giacobbe P et al; Canadian Network for Mood and Anxiety Treatments.  Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies.  J Affect Disord 2009; 117(Suppl 1):S44-53.
  24. National Collaborating Centre for Mental Health.  Depression.  The treatment and management of depression in adults.  London (UK): National Institute for Health and Clinical Excellence (NICE); 2009; October 64 p. (Clinical guideline; no. 90).  Available at www.nice.org.uk (accessed 2012 April 10).
  25. George MS, Lisanby SH, Avery D et al.  Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial.  Arch Gen Psychiatry 2010; 67(5):507-16.
  26. Janicak PG, Nahas Z, Lisanby SH et al.  Durability of clinical benefit with transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant major depression: assessment of relapse during a 6-month, multisite, open-label study.  Brain Stimul 2010; 3(4):187-99.
  27. Triggs WJ, Ricciuti N, Ward HE et al.  Right and left dorsolateral pre-frontal rTMS treatment of refractory depression: a randomized, sham-controlled trial.  Psychiatry Res 2010; 178(3):467-74.
  28. Mantovani A, Simpson HB, Fallon BA et al.  Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder.  Int J Neuropsychopharmacol 2010; 13(2):217-27.
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  30. Transcranial magnetic stimulation for depression.  Chicago, Illinois: Blue Cross and Blue Shield Association Technology Evaluation Center 2011; 26(3).
  31. Transcranial magnetic stimulation for the treatment of schizophrenia.  Chicago, Illinois: Blue Cross and Blue Shield Association Technology Evaluation Center 2011; 26(6).
  32. Mansur CG, Myczkowki ML, de Barros Cabral S et al.  Placebo effect after prefrontal magnetic stimulation in the treatment of resistant obsessive-compulsive disorder: a randomized controlled trial.  Int J Neuropsychopharmacol 2011; 14(10):1389-97.
  33. Short EB, Borckardt JJ, Anderson BS et al.  Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: A randomized, controlled pilot study.  Pain 2011; 152(11):2477-84.
  34. Ahmed MA, Darwish ES, Khedr EM et al.  Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia.  J Neurol 2011; 259(1):83-92. Epub 2011 Jun 14.
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  36. Transcranial Magnetic Stimulation as a Treatment of Depression and other Psychiatric/Neurologic Disorders.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2012 January) Surgery 2.01.50.
  37. Picht T, Schulz J, et al. Assessment of the influence of navigated transcranial magnetic stimulation on surgical planning for tumors in or near the motor cortex. Neurosurgery. 2012 May; 70(5):1248-56; discussion 1256-7.
  38. Säisänen L, Julkunen P, et al. Motor potentials evoked by navigated transcranial magnetic stimulation in healthy subjects. J Clin Neurophysiol. 2008 Dec; 25(6):367-72.
  39. Vajkoczy P, Picht T, et al. Utility of Navigated Brain Stimulation (NBS) in preoperative mapping of the motor cortex. Charite—Clinical Statement for NBS in Motor Mapping. Available at www.nexstim.com (accessed October 23, 2012).
  40. Dunning K, et al. Navigated Transcranial Magnetic Stimulation in Monitoring Stroke Recovery. NCT01005394. US National Institutes of Health ClinicalTrials.gov Available at www.clinicaltrials.gov (accessed October 23, 2012).
  41. FDA – 510k Summary for Nexstim Navigational Brain Stimualtion (NBS) System 4, and Nexstim NBS System 4 with NEXSPEECH®. Food and Drug Administration – Center for Devices and Radiologic Health (2011). Available at http://www.fda.gov (accessed October 23, 2012).
History
October 2011 New Policy: Investigational
March 2012 Policy updated with literature search through November 2011; references added and reordered; 14 older references removed; no change in policy statement
July 2013 Policy formatting and language revised.  Policy statement unchanged.  Title changed from "Transcranial Magnetic Stimulation as a Treatment of Depression and Other Psychiatric/Neurologic Disorders" to "Transcranial Magnetic Stimulation (TMS)".  Added code 0310T.
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Transcranial Magnetic Stimulation as a Treatment of Depression and Other Psychiatric/Neurologic Disorders