Blue Cross of Idaho Logo

Express Sign-on

Thank you for registering with Blue Cross of Idaho

If you are an Individual or Family Member, please register here.

If you are a Medicare Advantage or Medicare Supplement member, please register here.

 

MP 2.01.50 Transcranial Magnetic Stimulation as a Treatment of Depression and Other Psychiatric/Neurologic Disorders

Medical Policy    
Section
Medicine 
Original Policy Date
11/20/01
Last Review Status/Date
Reviewed with literature search/12:2014
Issue
12:2014
  Return to Medical Policy Index

 


Disclaimer

 

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.


Description

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; passing a rapidly alternating current through the coil wire, which produces 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 person 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 of depression 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), or deep stimulation with an H1 coil, are also being explored. In contrast to electroconvulsive therapy, TMS does not require anesthesia and does not induce a convulsion.

rTMS is also being tested as a treatment for a variety of other disorders including alcohol dependence, Alzheimer disease, neuropathic pain, obsessive-compulsive disorder, postpartum depression, Parkinson disease, stroke, posttraumatic stress disorder, panic disorder, epilepsy, dysphagia, Tourette syndrome, schizophrenia, migraine, spinal cord injury, fibromyalgia, and tinnitus. (See Policy No. 8.01.39 regarding rTMS for tinnitus.) In addition to the potential for altering interhemispheric imbalance, it has been proposed that high-frequency rTMS may facilitate neuroplasticity.

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 United States as a therapy for depression. Initially examined by FDA under a traditional 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 6-week course of antidepressant medication. The Brainsway™ H-Coil Deep TMS device (Brainsway Ltd.) received FDA clearance in 2013. This device is indicated for the treatment of depression in patients who have failed to respond to antidepressant medications in their current episode of depression and is a broader indication than that of the NeuroStar® TMS, which specifies the failure of 1 course of antidepressant medication (FDA product code: OBP).

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 electroconvulsive therapy (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 are posted online (www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4273b1_00-index.htm).

In 2013, the Cerena™ TMS device (Eneura Therapeutics) received de novo marketing clearance for the acute treatment of pain associated with migraine headache with aura. Warnings, precautions, and contraindications include the following:

  • The device is only intended for use by patients experiencing the onset of pain associated with a migraine headache with aura.
  • The device should not be used on headaches due to underlying pathology or trauma.
  • The device should not be used for medication overuse headaches.
  • The device has not been demonstrated as safe or effective when treating cluster headache or chronic migraine headache.
  • The device has not been shown to be effective when treating during the aura phase.
  • The device has not been demonstrated as effective in relieving the associated symptoms of migraine (photophobia, phonophobia, and nausea).
  • Safety and effectiveness have not been established in pregnant women, children under the age of 18, and adults over the age of 65.

The de novo 510(k) review process allows novel products with moderate or low-risk profiles and without predicates which would ordinarily require premarket approval as a class III device to be down-classified in an expedited manner and brought to market with a special control as a class II device.


Policy

 

Repetitive transcranial magnetic stimulation (rTMS) of the brain may be considered medically necessary as a treatment of major depressive disorder when all of the following conditions (1-3) have been met:

  1. Confirmed diagnosis of severe major depressive disorder (single or recurrent) documented by standardized rating scales that reliably measure depressive symptoms; AND
  2. Any one of the following (a, b, c, or d):
    1. Failure of 4 trials of psychopharmacologic agents including 2 different agent classes and 2 augmentation trials; OR
    2. Inability to tolerate a therapeutic dose of medications as evidenced by 4 trials of psychopharmacologic agents with distinct side effects; OR
    3. History of response to rTMS in a previous depressive episode (at least 3 months since the prior episode); OR
    4. Is a candidate for electroconvulsive therapy (ECT) and ECT would not be clinically superior to rTMS (e.g., in cases with psychosis, acute suicidal risk, catatonia or life-threatening inanition rTMS should NOT be utilized);

AND

  1. Failure of a trial of a psychotherapy known to be effective in the treatment of major depressive disorder of an adequate frequency and duration, without significant improvement in depressive symptoms, as documented by standardized rating scales that reliably measure depressive symptoms.

rTMS for major depressive disorder that does not meet the criteria listed above is considered investigational.

Continued treatment with rTMS of the brain as maintenance therapy is considered investigational.

Transcranial magnetic stimulation of the brain is considered investigational as a treatment of all other psychiatric/neurologic disorders, including but not limited to bipolar disorder, schizophrenia, obsessive-compulsive disorder, or migraine headaches. 


Policy Guidelines

 

Repetitive transcranial magnetic stimulation should be performed using an FDA-cleared device in appropriately selected patients, by physicians who are adequately trained and experienced in the specific techniques used. A treatment course should not exceed 5 days a week for 6 weeks (total of 30 sessions), followed by a 3-week taper of 3 TMS treatments in week 1, 2 TMS treatments the next week, and 1 TMS treatment in the last week.

Contraindications to rTMS include:

  1. Seizure disorder or any history of seizure with increased risk of future seizure; OR
  2. Presence of acute or chronic psychotic symptoms or disorders (such as schizophrenia, schizophreniform or schizoaffective disorder) in the current depressive episode; OR
  3. Neurologic conditions that include epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the central nervous system (CNS); OR
  4. Presence of an implanted magnetic-sensitive medical device located 30 centimeters or less from the TMS magnetic coil or other implanted metal items, including but not limited to a cochlear implant, implanted cardioverter defibrillator (ICD), pacemaker, vagus nerve stimulator, or metal aneurysm clips or coils, staples, or stents.

The following should be present for the administration of rTMS:

  1. An attendant trained in basic cardiac life support and the management of complications such as seizures, as well as the use of the equipment must be present at all times; AND
  2. Adequate resuscitation equipment including, for example, suction and oxygen; AND
  3. The facility must maintain awareness of response times of emergency services (either fire/ambulance or “code team”), which should be available within five minutes. These relationships are reviewed on at least a one year basis and include mock drills.

There are CPT category I codes for this procedure:

90867: Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; initial, including cortical mapping, motor threshold determination, delivery and management

90868: subsequent delivery and management, per session

90869: subsequent motor threshold re-determination with delivery and management

Code 90867 is reported once per course of treatment, and codes 90868 and 90869 cannot be reported for the same session.


Benefit Application
BlueCard/National Account Issues

State or federal mandates (e.g., FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.


Rationale 

 

This policy was created in 2001 and updated periodically with searches of the MEDLINE database, with the most recent literature update performed through October 30, 2014. At the time this policy was created, the U.S. Food and Drug Administration (FDA) had not cleared transcranial magnetic stimulation (TMS) as a therapeutic device for any neuropsychiatric disorder, including depression. In October 2008, the NeuroStar® TMS received FDA marketing clearance as a de novo device for therapy of patients with treatment-resistant depression (TRD) who have failed one 6-week course of antidepressant medication. Following is a summary of the key literature to date, focusing on systematic reviews and randomized controlled trials (RCTs). The evidence review is divided by indication and by key differences in treatment protocols, specifically high-frequency left dorsolateral prefrontal cortex (DLPFC) stimulation, lowfrequency (1-2 Hz) stimulation of the right DLPFC, combined high-frequency and low-frequency stimulation, and deep brain stimulation.

Depression

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.(1) Unless otherwise indicated in the trials described next, stimulation was set at 100% to 120% of motor threshold, clinical response was defined as an improvement of 50% or more on the Hamilton Rating Scale for Depression (HAM-D), and remission was considered to be a score of 7 or less on the HAM-D. Refer to the 2009 meta-analysis by Schutter for a summary of study characteristics and stimulation parameters used in trials conducted prior to 2008.(2)

Blue Cross and Blue Shield Technology Evaluation Center

TEC published assessments of repetitive TMS (rTMS) for depression in 2009, 2011, and 2013.(3-5) These TEC Assessments concluded that the available evidence does not permit conclusions regarding the effect of TMS on health outcomes. Limitations of the evidence include:

  • Equivocal efficacy in the 3 largest sham-controlled trial of TMS,
  • Uncertain clinical significance of the short-term anti-depressant effects found in meta-analyses, which are also at high risk of bias due to the inclusion of numerous small trials and potential for publication bias,
  • Limited evidence 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).

Agency for Healthcare Research and Quality

The Agency for Healthcare Research and Quality (AHRQ) published a comparative effectiveness review on nonpharmacologic interventions for TRD in adults in 2011.(6) Findings for the key questions (KQ) of the review follow.

Efficacy of nonpharmacologic interventions against other nonpharmacologic interventions (KQ 1a)

Direct evidence

  • The available head-to-head literature concerning the efficacy of the nonpharmacologic interventions for tier 1 TRD was limited to 2 fair trials (both in major depressive disorder-only populations). One compared electroconvulsive therapy (ECT) and rTMS, and the other compared ECT and ECT plus rTMS. They showed, with low strength of evidence, no differences between treatment options for depressive severity, response rates, and remission rates. No trial involved a direct comparison of psychotherapy with another nonpharmacologic intervention.

Indirect evidence

  • They identified trials that compared a nonpharmacologic intervention, generally rTMS, vagus nerve stimulation (VNS), or psychotherapy, with a control or sham procedure in tier 1 populations (ie, patients had 2 or more prior treatment failures with medications). The number of these trials with the same or similar control group was very small, so they could not pool them quantitatively. They assessed the potential benefits of nonpharmacologic interventions versus controls by calculating mean changes in depressive severity, relative risks of response, and relative risks of remission.
  • rTMS was beneficial relative to controls receiving a sham procedure for all 3 outcomes (severity of depressive symptoms, response rate, remission rate). rTMS produced a greater decrease in depressive severity (high strength of evidence). Specifically, rTMS averaged a decrease in depressive severity measured by the HAM-D (>5 points relative to sham control), and this change meets the minimum threshold of the 3-point HAM-D difference that is considered clinically meaningful. Response rates were greater with rTMS than sham (also high strength of evidence); those receiving rTMS were more than 3 times as likely to achieve a depressive response as patients receiving a sham procedure. Finally, rTMS was also more likely to produce remission than the control procedure (moderate strength of evidence); patients receiving rTMS were more than 6 times as likely to achieve remission as those receiving the sham.

Efficacy of nonpharmacologic interventions compared with antidepressant pharmacotherapies (KQ 1b)

Direct evidence

  • No direct evidence was identified for rTMS.

Maintenance of remission or prevention of relapse (KQ 2)

Direct evidence

  • With respect to maintaining remission (or preventing relapse), there were no direct comparisons involving ECT, rTMS, VNS, or cognitive behavioral therapy (CBT).

Indirect evidence

  • Three fair trials compared rTMS with a sham procedure and found no significant differences. However, too few patients were followed during the relapse prevention phases in 2 of the 3 studies, and patients in the third received a cointervention providing insufficient evidence for a conclusion.

AHRQ Authors’ Conclusions

The evidence review suggests that comparative clinical research on nonpharmacologic interventions in a TRD population is early in its infancy, and many clinical questions about efficacy and effectiveness remain unanswered. Interpretation of the data is substantially hindered by varying definitions of TRD and the paucity of relevant studies. The greatest volume of evidence is for ECT and rTMS. However, even for the few comparisons of treatments that are supported by some evidence, the strength of evidence is low for benefits, reflecting low confidence that the evidence reflects the true effect and indicating that further research is likely to change our confidence in these findings. This finding of low strength is most notable in 2 cases: ECT and rTMS did not produce different clinical outcomes in TRD, and ECT produced better outcomes than pharmacotherapy. No trials directly compared the likelihood of maintaining remission for nonpharmacologic interventions. The few trials addressing adverse events, subpopulations, subtypes, and health-related outcomes provided low or insufficient evidence of differences between nonpharmacologic interventions. The most urgent next steps for research are to apply a consistent definition of TRD, to conduct more head-to-head clinical trials comparing nonpharmacologic interventions with themselves and with pharmacologic treatments, and to delineate carefully the number of treatment failures following a treatment attempt of adequate dose and duration in the current episode.

High-Frequency rTMS of the Left DLPFC for TRD

There is a large body of evidence for the use of rTMS in the treatment of depression. The largest study (23 study sites) to date is a double-blind multicenter trial with 325 TRD patients randomly assigned to daily sessions of high-frequency active or sham rTMS (Monday to Friday for 6 weeks) of DLPFC.(7) TRD was defined as failure of at least 1 adequate course of antidepressant treatment. Patients had failed an average of 1.6 treatments in the current episode, with approximately half of the study population failing to benefit from at least 2 treatments. Loss to follow-up was similar in the 2 groups, with 301 (92.6%) patients completing at least 1 postbaseline assessment and an additional 8% of patients from both groups dropping out before the 4-week assessment. Intention-to-treat (ITT) analysis showed a trend favoring the
active rTMS group in the primary outcome measure (2 points on the Montgomery-Asberg Depression Rating Scale [MADRS]; p=0.057) and a modest (2-point) but significant improvement over sham treatment on the HAM-D. The authors reported that after 6 weeks of treatment, subjects in the active rTMS group were more likely to have achieved remission than the sham controls (14% vs 5%, respectively), 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.(8) This was a multicenter study involving patients with a moderate level of treatment resistance. The response rate using an ITT analysis was 14% for rTMS and 5% for sham (p=0.02). In this study, the site for stimulation was determined through pretreatment magnetic resonance imaging. Results from phase 2 (open treatment of nonresponders) and phase 3 (maintenance and follow-up) will be reported in the future.

Comparison With ECT

A 2013 systematic review by Berlim et al identified 7 RCTs with a total of 294 patients that directly compared rTMS and ECT treatment for patients with depression.(9) After an average of 15.2 sessions of high-frequency rTMS over the left DLPFC, 33.6% of patients were classified as remitters. This compared with 52% of patients who were classified as remitters following an average of 8.2 ECT sessions. The pooled odds ratio was 0.46, indicating a significant difference in outcome favoring ECT. There was no significant difference in dropout rates for the 2 treatments.

Deep TMS of the Left DLPFC for TRD

The RCT leading to 510(k) clearance of the Brainsway deep TMS system was conducted at 20 centers in the United States (n=13), Israel (n=4), Germany (n=2), and Canada (n=1).(10) The study included 229 patients with major depressive disorder who had not received benefit from 1 to 4 antidepressant trials or were intolerant to at least 2 antidepressant treatments. Per protocol analysis, which excluded 31 patients who did not receive adequate TMS treatment and 17 patients who did not meet the inclusion and exclusion criteria, the RCT showed a significant benefit for both response rate (38.4% vs 21.4%) and remission rate (32.6% vs 14.6%). Modified ITT analysis, which excluded the 17 patients who did not meet the inclusion/exclusion criteria, showed a significant benefit in both response rate (37% vs 22.8%) and remission rate (30.4% vs 15.8%). At the end of the maintenance period (16-week follow-up), the response rate remained significantly improved by deep TMS. Remission rates were not reported. ITT analysis found no significant benefit of treatment at 4 or 16 weeks.

Low-Frequency rTMS of the Right DLPFC or Bilateral Stimulation for TRD

Fitzgerald et al randomly assigned 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.(11) All patients who entered the study completed the double-blind randomized phase, which showed no difference between the 2 active treatments (left, 13.5% reduction; right, 15% reduction) and greater improvements in the MADRS scores compared with the sham group (0.76% reduction). Only 1 patient achieved 50% improvement during the initial 2 weeks. Then, only the subjects who showed at least 20% improvement at the end of the 10 sessions (15 active, 2 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, respectively). Seven patients (18% of 40) showed a clinical response of greater than 50% by the end of the 4 weeks.

In a subsequent study, Fitzgerald et al randomly assigned 50 patients with TRD to sequential bilateral active or sham rTMS.(12) After 2 weeks of treatment, 3 subjects had dropped out of the sham treatment group, and there was a slight but nonsignificant improvement favoring the active group for the MADRS (26.2 vs 30.9, respectively) and the Beck Depression Inventory (BDI; 18.3 vs 21.6, respectively). 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 (9 active, 2 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 3 was continued for 15 subjects in the active group and 7 subjects in the sham group. By week 6, 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 6 were 8.9 on the MADRS and 9.2 on the BDI.

Another multicenter double-blind trial randomly assigned 130 patients with TRD to 5 sessions per week of either 1- or 2-Hz rTMS over the right DLPFC.(13) Sixty-eight patients (52%) completed 4 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.(14) Overall reductions in the HAM-D-24 from baseline to 3 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

Berlim et al reported a 2013 meta-analysis on the effect of rTMS for accelerating and enhancing the clinical response to antidepressants.(15) Data were obtained from 6 double-blind RCTs with a total of 392 patients. Response was defined as a 50% or greater reduction in the HDRS or the MADRS. At an average of 2.7 weeks after the start of the combined treatments, response rates were significantly higher with rTMS plus antidepressant treatment compared with sham rTMS (43.3% vs 26.8%; odds ratio [OR], 2.50); remission rates were not significantly different. At the end of the studies (average, 6.8 weeks), response and remission rates were significantly higher with combined high-frequency rTMS plus antidepressant treatment compared with sham rTMS (response, 62% vs 46%; OR= -1.9; remission, 53.8% vs 38.6%; OR=2.42).

A 2012 study examined the efficacy of ultra-high-frequency (30 Hz) rTMS over the left prefrontal cortex in moderate to severely depressed patients who were taking medication.(16) Sham treatment consisted of low-frequency stimulation to the left prefrontal cortex. No benefit of rTMS for depressive symptoms was found when lithium was added as a covariate. Ultra-high-frequency rTMS was found to improve performance on the Trail-Making Test, which covaried with improvement of psychomotor disability. Additional research on whether adjunctive rTMS can improve response to pharmacologic treatment as a first-line therapy is needed.

Maintenance Therapy

In 2014, Dunner et al reported 1-year follow-up with maintenance therapy from a large multicenter observational study (42 sites) of rTMS for patients with TRD.(17) A total of 257 patients agreed to participate in the follow-up study of 307 who were initially treated with rTMS. Of these, 205 completed the 12-month follow-up, and 120 patients had met the Inventory of Depressive Symptoms-Self Report response or remission criteria at the end of treatment. Ninety-three of the 257 patients (36.2%) who enrolled in the follow-up study received additional rTMS (mean, 16.2 sessions). Seventy-five of the 120 patients (62.5%) who met response or remission criteria at the end of the initial treatment phase (including a 2 month taper phase) continued to meet response criteria through follow-up.

A variety of maintenance schedules are being studied. Richieri et al used propensity-adjusted analysis of observational data and found that the group of patients who had maintenance rTMS tapered over 20 weeks (from 3 times per week to once a month) had a significantly reduced relapse rate compared with patients who had no additional treatment (37.8% vs 81.8%).(18) Connolly et al reported that in the first 100 cases treated at their institution, the response rate was 50.6% and the remission rate was 24.7%.(19) At 6 months after the initial rTMS treatment, 26 of 42 patients (62%) who received tapered maintenance therapy (from 2 sessions per week for the first 3 weeks to monthly) maintained their response. In another 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.(20) During the 24-week follow-up, 10 of 99 patients relapsed, 38 had symptom worsening, and of these 32 (84%) had symptomatic benefit with adjunctive rTMS.

Fitzgerald et al reported a prospective open-label trial of clustered maintenance rTMS for patients with TRD.(21) All patients had received a second successful course of rTMS following relapse and were then treated with monthly maintenance therapy consisting of 5 rTMS treatments over a 2.5-day period (Friday evening, Saturday, and Sunday). Of 35 patients, 25 (71%) relapsed at a mean of 10.2 months (range, 2-48 months).

Additional data are needed related to durability of effect and to maintenance therapy.

Alzheimer Disease

Ahmed et al randomized 45 patients with probable Alzheimer disease to 5 sessions of bilateral highfrequency rTMS, bilateral low-frequency rTMS, or sham TMS over the DLPFC.(22) 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 3 months after treatment, the high-frequency rTMS group improved significantly more than the other 2 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, from 20.1 to 24.7 on the Instrumental Daily Living Activity scale, and from 5.9 to 2.6 on the Geriatric Depression Scale.

Rabey et al reported an industry-sponsored randomized double-blind trial of rTMS with cognitive training (NeuroAD system) in15 patients with probable mild to moderate Alzheimer disease.(23) Patients received 5 sessions per week for 6 weeks over 6 different brain areas, followed by biweekly sessions for 3 months. Specific cognitive tasks were designed for the 6 targeted brain regions. These included syntax and grammar for Broca area, comprehension and categorization for Wernicke area, action naming, object naming and spatial memory tasks for the right and left DLPFC, and spatial attention tasks for the right and left somatosensory association cortex. After 6 weeks of treatment, there was an improvement in the average Alzheimer Disease Assessment Scale, cognitive subsection (ADAS-cog) score of 3.76 points in the rTMS group compared with 0.47 in the placebo group. After 4.5 months of treatment, the ADAS-cog score in the rTMS group had improved by 3.52 points compared with a worsening of 0.38 in the placebo group. The Clinical Global Impression of Change improved significantly by an average of 3.57 after 6 weeks and 3.67 after 4.5 months compared with 4.25 and 4.29, respectively, in the placebo group.

Attention-Deficit/Hyperactivity Disorder

In 2012, Weaver et al reported a randomized, sham-controlled crossover study of rTMS in 9 adolescents/young adults with attention deficit/hyperactivity disorder (ADHD).(24) rTMS was administered in 10 sessions over 2 weeks, with 1 week of no TMS between the active and sham phases. The clinical global impression and ADHD-IV scales improved in both conditions over the course of the study, with no significant differences between the active and sham phases.

Amyotrophic Lateral Sclerosis or Motor Neuron Disease

A Cochrane review from 2013 identified 3 RCTs with a total of 50 participants with amyotrophic lateral sclerosis (ALS) that compared rTMS with sham TMS.(25) All of the trials were considered to be of poor methodologic quality. Heterogeneity prevented pooling of results, and the high rate of attrition further increased the risk of bias. The review concluded that evidence is currently insufficient to draw conclusions about the efficacy and safety of rTMS in the treatment of ALS.

Bulimia Nervosa

In 2008, Walpoth et al reported no evidence of efficacy of rTMS in a small trial (n=14) of patients with bulimia nervosa.(26)

Chronic Pain

A 2014 Cochrane review on noninvasive brain stimulation techniques identified 30 RCTs (528 patients) on TMS for chronic pain.(27) There was low to very low quality evidence that low frequency rTMS or rTMS to the DLPFC is ineffective. Studies on high-frequency rTMS to the motor cortex were heterogeneous, of low quality, and did not demonstrate a significant effect. Due the low quality of the identified studies, future studies could have a substantial impact on the conclusions.

Dysphagia

rTMS for the treatment of dysphagia following stroke has been examined in small RCTs. One study randomized 26 patients to rTMS or sham over the affected esophageal motor area of the cortex.(28) Ten minutes of rTMS over 5 days reduced both dysphagia on the Dysphagic Outcome and Severity Scale and disability measured by the Barthel Index. There was a trend for improved hand grip strength in the rTMS group. Blinded assessment showed that the effects were maintained at 1-month and 2-month follow-up. Another study randomized 30 patients with dysphagia following stroke or traumatic brain injury to highfrequency rTMS, low-frequency rTMS, or sham stimulation.(29) Active or sham rTMS was administered bilaterally over the anterolateral scalp over a period of 2 weeks. Swallowing scale scores improved in both the low-frequency and sham groups. Improvement in videofluoroscopic evaluation was greater in the low-frequency rTMS group than the other 2 groups. Blinding of evaluators was not described.

Study in a larger number of subjects is needed to determine the efficacy of this treatment with greater certainty.

Epilepsy

In 2012, Sun et al reported a double-blind RCT of low-frequency rTMS to the epileptogenic zone for refractory partial epilepsy.(30) Sixty patients were randomized into 2 groups; one group received 2 weeks of rTMS at 90% of resting motor threshold, and the other group received rTMS at 20% of resting motor threshold. Outcomes were measured for 8 weeks after the end of treatment. With ITT analysis, highintensity rTMS resulted in a significant decrease in seizures when compared with baseline (from 8.9 per week at baseline to 1.8 per week at follow-up) and when compared with low-intensity rTMS (from 8.6 at baseline to 8.4 per week at follow-up). High-intensity rTMS also decreased interictal discharges (from 75.1 to 33.6 per hour) and improved ratings on the Symptom Checklist‒90. These initial results are promising, but require substantiation in additional trials.

Fibromyalgia

A 2012 systematic review included 4 studies on transcranial direct current stimulation and 5 on rTMS for treatment of fibromyalgia pain.(31) Three of the 5 trials were considered to be high quality. Four of the 5 were double-blind RCTs; the fifth included study was a case series of 4 patients who were blinded to treatment. Quantitative meta-analysis was not conducted due to variability in brain site, stimulation frequency/intensity, total number of sessions, and follow-up intervals, but 4 of the 5 studies on rTMS reported significant decreases in pain. Greater durability of pain reduction was observed with stimulation of the primary motor cortex compared with the DLPFC.

One of the studies included in the systematic review was a small 2011 trial that was conducted in the United States by Short et al.(32) 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 2 weeks after treatment, there was a significant change from baseline in average visual analog scale 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 with 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.

A 2013 report evaluated the effect of very low-intensity rTMS in a randomized sham-controlled doubleblinded trial of 54 patients with fibromyalgia.(33) Six weeks of rTMS (once per week) with 33 magnetic coils around the head resulted in a significant improvement in pain thresholds (+28%) across the 8 sessions and in the ability to perform daily activities (11%), perceived chronic pain (-39%) and sleep quality (75%) beginning at week 6. Fatigue, anxiety, depression, and severity of headaches were unaffected by treatment.

Additional study is needed to determine effective treatment parameters in a larger number of subjects and to evaluate durability of the effect.

Migraine Headache

A pivotal randomized, double-blind, multicenter, sham-controlled trial was performed with the Cerena™ TMS device to demonstrate safety and effectiveness for the de novo application.(34) Enrolled in the study were 201 patients with a history of an aura preceding more than 30% of headaches with moderate or severe headache severity for approximately 90% of migraine attacks. Following a month baseline phase to establish the frequency and severity of migraine, patients were randomized to a treatment phase consisting of 3 treatments or 3 months, whichever occurred first. Patients were instructed to treat their migraine headache during the aura phase and to record their pain severity (0-3), severity of associated migraine symptoms (photophobia, phonophobia, nausea), presence of vomiting, and use of rescue medications at the time of treatment and at 1, 2, 24, 48 hours after treatment. The primary end point was the proportion of patients who were pain-free 2 hours after treatment. Of the 201 patients enrolled, 164 recorded at least 1 treatment and 113 recorded at least 1 treatment when there was pain. Post hoc analysis of these 113 patients showed a benefit of the device for the primary end point (37.74% pain free after 2 hours for Cerena™ and 16.67% for sham, p=0.018) and for the proportion of subjects who were pain free after 24 hours (33.96% for Cerena™, 10% for sham; p=0.002). Active treatment was not inferior to sham for the proportion of subjects free of photophobia, suggesting that the device does not worsen photophobia. However, the device was not noninferior to sham for the proportion of subjects free of nausea and phonophobia.

These results are limited by the 46% dropout rate and post hoc analysis. According to the FDA labeling, the device has not been demonstrated as safe or effective when treating cluster headache, chronic migraine headache, or when treating migraine headache during the aura phase. The device has not been demonstrated as effective in relieving the associated symptoms of migraine (photophobia, phonophobia, nausea).(34)

Obsessive-Compulsive Disorder

A 2013 meta-analysis included 10 small RCTs totaling 282 patients with obsessive-compulsive disorder.(35) Response rates of rTMS augmentation therapy were 35% for active and 13% for sham rTMS. The pooled odds ratio was 3.39, and the number needed to treat was 5. There was no evidence of publication bias. Exploratory subgroup analysis suggested that the 2 most promising stimulation parameters were lowfrequency rTMS and non-DLPFC regions (ie, orbitofrontal cortex or supplementary motor area). Further study focusing on these stimulation parameters is needed.

Panic Disorder

A 2014 Cochrane review identified 2 RCTs with a total of 40 patients that compared low frequency rTMS with sham rTMS over the right DLPFC.(36) The larger of the 2 studies was a randomized, double-blind, sham-controlled trial in 21 patients with panic disorder with comorbid major depression.(37) Response was defined as a 40% or greater decrease on the Panic Disorder Severity Scale and a 50% or greater decrease on HAM-D. After 4 weeks of treatment, the response rate for panic was 50% with active rTMS and 8% with sham. The study had a high risk of attrition bias. The overall quality of evidence for the 2 studies was considered to be low, and the sample sizes were small, precluding any conclusions about the efficacy of rTMS for panic disorder.'

Parkinson Disease

A systematic review from 2009 included 10 RCTs with a total of 275 patients with Parkinson disease.(38) Seven of the studies were double-blind, 1 was not blinded, and 2 of the studies did not specify whether the raters were blinded. In studies that used high-frequency rTMS, there was a significant improvement on the Unified Parkinson’s Disease Rating Scale (UPDRS) with a moderate effect size of -0.58. For lowfrequency rTMS, the results were heterogeneous and did not significantly reduce the UPDRS. The analyzed studies varied in outcomes reported, rTMS protocol, patient selection criteria, demographics, stages of Parkinson disease and duration of follow-up, which ranged from immediate to 16 weeks after treatment.

In 2012, Benninger et al reported a randomized double-blind sham-controlled trial of brief (6 seconds) very-high-frequency (50 Hz) rTMS over the motor cortex in 26 patients with mild to moderate Parkinson disease.(39) Eight sessions of 50-Hz rTMS did not improve gait, bradykinesia, or global and motor scores on the UPDRS compared with the sham-treated group. Activities of daily living were significantly improved a day after the intervention, but the effect was no longer evident at 1 month after treatment. Functional status and self-reported well-being were not affected by the treatment. No adverse effects of the very high-frequency stimulation were identified.

Another study from 2012 randomized 20 patients with Parkinson disease to 12 brief sessions (6 minutes) of high-frequency (5-Hz) rTMS or sham rTMS over the leg area of the motor cortex followed by treadmill training.(40) Blinded evaluation showed a significant effect of rTMS combined with treadmill training on neurophysiologic measures, and change in fast walking speed and the timed up and go task. Mean treadmill speed improved to a similar extent in the active and sham rTMS groups.

A 2013 exploratory, multicenter, double-blind trial randomized 106 patients to 8 weeks of 1-Hz rTMS, 10 Hz rTMS, or sham stimulation over the supplementary motor area.(41) At 9 weeks, all groups showed a similar amount of improvement. At the 20-week follow-up, only the 1 Hz group showed a significant improvement (6.84 points) in the primary outcome measure, the UPDRS part III. There was no significant improvement in other outcome measures.

Additional study with a larger number of subjects and longer follow-up is needed to determine if rTMS improves motor symptoms in patients with Parkinson disease.

Postpartum Depression

Myczkowski et al conducted a double-blind, sham-controlled study of 14 patients with postpartum depression randomized to 20 sessions of active or sham rTMS over the left DLPFC.(42) A positive response to treatment was defined as a reduction of at least 30% in the HAM-D and Edinburgh Postnatal Depression Scale (EPDS). At 2 weeks after the end of treatment, the active rTMS group showed significant improvements in the HAM-D, Global Assessment Scale, Clinical Global Impression and Social
Adjustment Scale. The difference in the EPDS (reduction of 39.4% vs 6.2% for sham) did not reach statistical significance in this small study, and there were marginal cognitive and social improvements. In addition, results were presented as mean values, rather than by the proportion of patients who showed clinically meaningful improvement.

Posttraumatic Stress Disorder

The efficacy of rTMS for posttraumatic stress disorder (PTSD) has been examined in several small RCTs. A 2004 study randomized 24 patients with PTSD to 10 sessions of low-frequency (1-Hz), high-frequency (10-Hz), or sham rTMS over the right DLPFC.(43) Blinded assessment 2 weeks after the intervention found that high-frequency rTMS improved the self-reported PTSD checklist (PCL) by 29.3%, the clinician evaluation on the Treatment Outcome PTSD scale by 39.0%, the HAM-D by 25.9%, and the Hamilton Anxiety Rating Scale by 44.1%. Scores for the sham and low-frequency group were not significantly improved.

In 2012, Watts et al reported a double-blind trial with 20 patients randomized to low-frequency rTMS or sham over the right DLPFC.(44) Blinded evaluation at the end of treatment showed clinically significant improvements in the Clinician Administered PTSD Scale (CAPS) and the PCL compared with sham. Depressive and anxiety symptoms also improved in the rTMS group. Six of the 10 rTMS patients showed a degradation of symptoms between the immediate posttreatment assessment and the 2-month posttreatment follow-up.

In another double-blind trial, 30 patients with PTSD were randomized to deep, high-frequency rTMS after brief exposure to a script of the traumatic event, rTMS after a script of a nontraumatic event, or sham stimulation after a brief script of the traumatic event.(45) Patients received 3 treatment sessions per week for 4 weeks, and response was defined as a 50% or greater improvement in CAPS score. ITT analysis showed a significant improvement in the total CAPS score in the exposure plus stimulation group (24.3) compared with rTMS alone (7.9) or traumatic exposure with sham rTMS (9.1). The greatest improvement was in the intrusive component of CAPS. Heart rate responses to the traumatic script were also reduced over the 4 weeks of treatment. The proportion of patients who showed a response to treatment was not reported and the durability of the response was not assessed.

Section Summary

Several small RCTs have reported improvement of PTSD with rTMS over the right dorsolateral cortex. Results of high-frequency versus low-frequency stimulation are conflicting, and durability of the response has not been assessed. Additional study is needed.

Schizophrenia

One of the largest areas of TMS research outside of depressive disorders is the treatment of auditory hallucinations in schizophrenia resistant to pharmacotherapy. In 2011, TEC published an Assessment of TMS as an adjunct treatment for schizophrenia.(46) 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, 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 Assessment concluded that the available evidence is insufficient to demonstrate that TMS is effective in the treatment of schizophrenia.

A 2012 meta-analysis included 17 randomized, double-blind, sham-controlled trials (N=337) of the effect of rTMS on auditory hallucinations.(47) When measured at the end of treatment, the mean effect size of rTMS directed at the left temporoparietal area was 0.40 (moderate), and the effect size of rTMS directed at all brain regions was 0.33 (small). For the 5 trials that examined outcomes of rTMS 1 month after treatment, the effect was no longer significant.

A 2013 meta-analysis included 17 RCTs (N=398) that evaluated low-frequency rTMS of the left temporoparietal cortex for the treatment of auditory hallucinations.(48) The mean effect size for severity of auditory hallucinations (all studies) was -0.42. The odds ratio for the response to treatment, defined as a 30% or greater reduction, was 2.94 (6 trials, N=181).

A small (N=18) double-blind, randomized, sham-controlled trial from 2012 found no significant effect of deep rTMS with an H1 coil on auditory hallucinations.(49)

Section Summary

The evidence on rTMS for the treatment of auditory hallucinations in schizophrenia consists of a number of small RCTs. Evidence to date shows small-to-moderate effects on hallucinations when measured at the end of treatment, but evidence suggests that the effect is not durable.

Stroke

There are a number of RCTs and systematic reviews that have evaluated rTMS for recovery from stroke.

A 2013 Cochrane review included 19 RCTs with a total of 588 participants on the effect of TMS for improving function after stroke.(50) The 2 largest trials (N=183) showed that rTMS was not associated with a significant improvement in the Barthel Index. Four trials (N=73) found no significant effect for motor function. Subgroup analysis for different stimulation frequencies or duration of illness also did not show a significant benefit of rTMS when compared with sham rTMS or no treatment. The review  concluded that current evidence does not support the routine use of rTMS for the treatment of stroke.

Hsu et al reported a meta-analysis of the effect of rTMS on upper-limb motor function in patients with stroke in 2012.51 Eighteen RCTs with a total of 392 patients were included in the meta-analysis. Most of the studies were double blind (n=11) or single blind (n=3). Eight studies applied low-frequency (1-Hz) rTMS over the unaffected hemisphere, 5 applied high-frequency (5-Hz) rTMS over the affected hemisphere, and 2 used both low- and high-frequency stimulation. Outcomes included kinematic motion analyses (5 trials), hand grip (2 trials), and the Wolf Motor Function Test (2 trials). Meta-analysis of results showed a moderate effect size (0.55) for rTMS on motor outcome, with a greater effect size of rTMS in patients with subcortical stroke (mean effect size, 0.73) compared with nonspecified lesion sites (mean effect size, 0.45), and for studies applying low-frequency rTMS (mean effect size, 0.69) compared with high-frequency rTMS (effect size, 0.41). Effect size of 0.5 or greater was considered to be clinically meaningful.

A 2014 meta-analysis assessed the effect of rTMS on recovery of hand function and excitability of the motor cortex after stroke.(52) Eight RCTs with a total of 273 participants were included in the review. The quality of the studies was rated moderate to high, although the size of the studies was small. There was variability in the time since stroke (5 days to 10 years), in the frequency of rTMS applied (1 Hx to 25 Hx for 1 second to 25 min/d), and the stimulation sites (primary motor cortex or premotor cortex of the unaffected hemisphere). Meta-analysis found a positive effect on finger motor ability (4 studies; N=79; standardized mean difference, 0.58) and hand function (3 studies; N=74; standardized mean difference, -0.82), but no significant change in motor evoked potential (n=43) or motor threshold (n=62).

Section Summary

Evidence consists of a number of RCTs and meta-analyses of the effect of rTMS on recovery from stroke. Results are conflicting, and efficacy may depend on the location of the stroke and frequency of the rTMS. Additional study is needed to determine whether rTMS facilitates standard physical therapy in patients with stroke.

Substance Abuse and Craving

Jansen et al reported a 2013 meta-analysis of the effect of rTMS and transcranial direct current stimulation (tDCS) of the DLPFC on substance dependence (alcohol, nicotine, cocaine, marijuana) or craving for high palatable food.(53) Seventeen double-blind, sham-controlled RCTs that used highfrequency stimulation were included in the analysis. The standardized effect size was 0.476, indicating a medium effect size for active stimulation over sham, although there was significant heterogeneity in the
included studies. No significant differences were found in the effectiveness of rTMS versus tDCS, the different substances, or the side of stimulation.

Clinical Input Received From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 1 physician specialty society and 3 academic medical centers while this policy was under review in 2014. The reviewers considered rTMS to be medically necessary for TRD. Input agreed with the proposed criteria for treatment of TRD with rTMS, as included in the policy statement.

Summary of Evidence

The literature on repetitive TMS (rTMS) for treatment-resistant depression (TRD) includes numerous 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 to 3 times that of sham controls, with approximately 15% to 25% of patients meeting the definition of clinical response. Based on the short-term benefit observed in randomized controlled trials, clinical input, and the lack of alternative treatments aside from electroconvulsive therapy (ECT) in patients with TRD, rTMS may be considered medically necessary in patients with TRD who meet specific criteria.

For other psychiatric/neurologic conditions, the evidence is insufficient to determine whether rTMS leads to improved outcomes. The available clinical trials are small and report mixed results for a variety of conditions other than depression. There are no large, high-quality trials for any of these other conditions. Therefore, rTMS is considered investigational for other psychiatric/neurologic conditions.

Practice Guidelines and Position Statements

The American Psychiatric Association (APA) 2010 practice guidelines for the treatment of patients with major depressive disorder states that treatment in the acute phase should be aimed at inducing remission of the major depressive episode and achieving a full return to the patient’s baseline level of functioning [I, Recommended with substantial clinical confidence]. Acute phase treatment may include pharmacotherapy, depression-focused psychotherapy, the combination of medications and psychotherapy, or other somatic therapies such as ECT, TMS, or light therapy. APA states that a number of strategies are available when a change in the treatment plan seems necessary, such as transdermal selegiline, a relatively selective MAO B inhibitor with fewer dietary and medication restrictions, or transcranial magnetic stimulation could also be considered [II, Recommended with moderate clinical confidence].(54)

A group of European experts was commissioned to establish evidence-based guidelines on the therapeutic use of rTMS.(55) The guidelines included evidence published up until March 2014. For most indications there was an absence of sufficient evidence, and the committee could provide no recommendation. Indications which had a recommendation of a definite effect were neuropathic pain and depression. Indications which had a recommendation for a possible or probable effect included complex
regional pain syndrome, Parkinson disease, motor stroke, hemispatial neglect, epilepsy, tinnitus, anxiety disorders, auditory hallucinations, negative symptom of schizophrenia, addiction and craving.

In 2007 the National Institute for Health and Care Excellence (NICE) published an Interventional Procedure Guideline (IPG) 242, which stated that current evidence suggests no major safety concerns for the use of TMS in the treatment of depression. There was uncertainty related to the clinical efficacy of TMS, which may depend on a number of factors such as higher intensity, greater frequency, bilateral application, and/or longer treatment durations than have appeared in evidence to date. TMS should be performed in research studies designed to evaluate these factors.(56) The opinion was repeated in the NICE 2009 Clinical Guideline 90.(57)

NICE guidance in 2006 on the management of bipolar disorder in adults, children, and adolescents in primary and secondary care states that TMS should not be routinely used for acute depressive episodes in people with bipolar disorder. The guidance states that TMS is not of proven efficacy for bipolar disorder and that when compared with sham TMS, the participants receiving sham treatment had lower end point mania symptom scores.(58)

2006 Practice Guidelines on the evaluation and treatment of depression, psychosis, and dementia in Parkinson disease from the American Academy of Neurology concluded that there is insufficient evidence to support or refute the efficacy of TMS or ECT in the treatment of depression associated with Parkinson disease (level U; data inadequate or conflicting given current knowledge, treatment is unproven).(59)

The Canadian Network for Mood and Anxiety Treatments updated their clinical guidelines on neurostimulation therapies for the management of major depressive disorder in adults.(60) The evidence reviewed supported ECT as a first-line treatment under specific circumstances; when used in patients who have failed to respond to 1 or more adequate antidepressant medication trials, ECT response rates have been estimated to be 50% to 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 1 openlabel case series was identified.

U.S. Preventive Services Task Force Recommendations
Not applicable.

Medicare National Coverage
There is no national coverage determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of local Medicare carriers.

References:

 
  1. 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. Sep 2007;116(3):165-173. PMID 17655557
  2. 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. Jan 2009;39(1):65-75. PMID 18447962
  3. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Transcranial magnetic stimulation for depression. TEC Assessments. 2009;Volume 24, Tab 5.
  4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Transcranial magnetic stimulation for depression. TEC Assessments. 2011;Volume 26, Tab 3.
  5. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Transcranial magnetic stimulation for depression. TEC Assessments. 2013;Volume 28, Tab 9.
  6. Gaynes B, Lux L, Lloyd S, et al. Nonpharmacologic Interventions for Treatment-Resistant Depression in Adults. Comparative Effectiveness Review No. 33. (Prepared by RTI International-University of North Carolina (RTI-UNC) Evidence based Practice Center under Contract No. 290-02-0016I.) AHRQ Publication No. 11-EHC056-EF. Rockville, MD: Agency for Healthcare Research and Quality. 2011;
    http://www.effectivehealthcare.ahrq.gov/ehc/products/76/792/TRD_CER33_20111110.pdf. Accessed April, 2014.
  7. O'Reardon JP, Solvason HB, Janicak PG, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. Dec 1 2007;62(11):1208-1216. PMID 17573044
  8. 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. May 2010;67(5):507-516. PMID 20439832
  9. Berlim MT, Van den Eynde F, Daskalakis ZJ. Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials. Depress Anxiety. Jul 2013;30(7):614-623. PMID 23349112
  10. U.S. Food and Drug Administration. 510(k) Summary: Brainsway deep TMS System. 2013; http://www.accessdata.fda.gov/cdrh_docs/pdf12/k122288.pdf. Accessed February, 2014.
  11. Fitzgerald PB, Brown TL, Marston NA, et al. Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. Oct 2003;60(10):1002-1008. PMID 14557145
  12. 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. Jan 2006;163(1):88-94. PMID 16390894
  13. 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. Dec 2006;9(6):655-666. PMID 16959055
  14. 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. Aug 15 2010;178(3):467-474. PMID 20643486
  15. Berlim MT, Van den Eynde F, Daskalakis ZJ. High-frequency repetitive transcranial magnetic stimulation accelerates and enhances the clinical response to antidepressants in major depression: a meta-analysis of randomized, double-blind, and sham-controlled trials. J Clin Psychiatry. Feb 2013;74(2):e122-129. PMID 23473357
  16. Ullrich H, Kranaster L, Sigges E, et al. Ultra-high-frequency left prefrontal transcranial magnetic stimulation as augmentation in severely ill patients with depression: a naturalistic sham-controlled, double-blind, randomized trial. Neuropsychobiology. 2012;66(3):141-148. PMID 22948250
  17. Dunner DL, Aaronson ST, Sackeim HA, et al. A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period. J Clin Psychiatry. Sep 16 2014. PMID 25271871
  18. Richieri R, Guedj E, Michel P, et al. Maintenance transcranial magnetic stimulation reduces depression relapse: a propensity-adjusted analysis. J Affect Disord. Oct 2013;151(1):129-135. PMID 23790811
  19. Connolly KR, Helmer A, Cristancho MA, et al. Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. J Clin Psychiatry. Apr 2012;73(4):e567-573. PMID 22579164
  20. 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. Oct 2010;3(4):187-199. PMID 20965447
  21. Fitzgerald PB, Grace N, Hoy KE, et al. An open label trial of clustered maintenance rTMS for patients with refractory depression. Brain Stimul. May 2013;6(3):292-297. PMID 22683273
  22. 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. Jan 2012;259(1):83-92. PMID 21671144
  23. Rabey JM, Dobronevsky E, Aichenbaum S, et al. Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer's disease: a randomized, doubleblind study. J Neural Transm. Oct 18 2012. PMID 23076723
  24. Weaver L, Rostain AL, Mace W, et al. Transcranial magnetic stimulation (TMS) in the treatment of attentiondeficit/ hyperactivity disorder in adolescents and young adults: a pilot study. J ECT. Jun 2012;28(2):98-103. PMID 22551775
  25. Fang J, Zhou M, Yang M, et al. Repetitive transcranial magnetic stimulation for the treatment of amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database Syst Rev. 2013;5:CD008554. PMID 23728676
  26. 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. PMID 18087209
  27. O'Connell NE, Wand BM, Marston L, et al. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2014;4:CD008208. PMID 24729198
  28. Khedr EM, Abo-Elfetoh N, Rothwell JC. Treatment of post-stroke dysphagia with repetitive transcranial magnetic stimulation. Acta Neurol Scand. Mar 2009;119(3):155-161. PMID 18771521
  29. Kim L, Chun MH, Kim BR, et al. Effect of repetitive transcranial magnetic stimulation on patients with brain injury and Dysphagia. Ann Rehabil Med. Dec 2011;35(6):765-771. PMID 22506204
  30. Sun W, Mao W, Meng X, et al. Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: a controlled clinical study. Epilepsia. Oct 2012;53(10):1782-1789. PMID 22950513
  31. Marlow NM, Bonilha HS, Short EB. Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. Pain Pract. Feb 2013;13(2):131-145. PMID 22631436
  32. 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. Nov 2011;152(11):2477-2484. PMID 21764215
  33. Maestu C, Blanco M, Nevado A, et al. Reduction of pain thresholds in fibromyalgia after very low-intensity magnetic stimulation: A double-blinded, randomized placebo-controlled clinical trial. Pain Res Manag. Nov-Dec 2013;18(6):e101-106. PMID 24308025
  34. U.S. Food and Drug Administration. De Novo classification request for cerena transcranial magnetic stimulator (TMS) device. 2013; http://www.accessdata.fda.gov/cdrh_docs/reviews/K130556.pdf. Accessed April, 2014.
  35. Berlim MT, Neufeld NH, Van den Eynde F. Repetitive transcranial magnetic stimulation (rTMS) for obsessivecompulsive disorder (OCD): an exploratory meta-analysis of randomized and sham-controlled trials. J Psychiatr Res. Aug 2013;47(8):999-1006. PMID 23615189
  36. Li H, Wang J, Li C, et al. Repetitive transcranial magnetic stimulation (rTMS) for panic disorder in adults. Cochrane Database Syst Rev. 2014;9:CD009083. PMID 25230088
  37. Mantovani A, Aly M, Dagan Y, et al. Randomized sham controlled trial of repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex for the treatment of panic disorder with comorbid major depression. J Affect Disord. Jan 10 2013;144(1-2):153-159. PMID 22858212
  38. Elahi B, Elahi B, Chen R. Effect of transcranial magnetic stimulation on Parkinson motor function--systematic review of controlled clinical trials. Mov Disord. Feb 15 2009;24(3):357-363. PMID 18972549
  39. Benninger DH, Iseki K, Kranick S, et al. Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease. Neurorehabil Neural Repair. Nov 2012;26(9):1096-1105. PMID 22593114
  40. Yang YR, Tseng CY, Chiou SY, et al. Combination of rTMS and treadmill training modulates corticomotor inhibition and improves walking in Parkinson disease: a randomized trial. Neurorehabil Neural Repair. Jan 2013;27(1):79-86. PMID 22785003
  41. Shirota Y, Ohtsu H, Hamada M, et al. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology. Apr 9 2013;80(15):1400-1405. PMID 23516319
  42. Myczkowski ML, Dias AM, Luvisotto T, et al. Effects of repetitive transcranial magnetic stimulation on clinical, social, and cognitive performance in postpartum depression. Neuropsychiatr Dis Treat. 2012;8:491-500. PMID 23118543
  43. Cohen H, Kaplan Z, Kotler M, et al. Repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in posttraumatic stress disorder: a double-blind, placebo-controlled study. Am J Psychiatry. Mar 2004;161(3):515-524. PMID 14992978
  44. Watts BV, Landon B, Groft A, et al. A sham controlled study of repetitive transcranial magnetic stimulation for posttraumatic stress disorder. Brain Stimul. Jan 2012;5(1):38-43. PMID 22264669
  45. Isserles M, Shalev AY, Roth Y, et al. Effectiveness of deep transcranial magnetic stimulation combined with a brief exposure procedure in post-traumatic stress disorder--a pilot study. Brain Stimul. May 2013;6(3):377-383. PMID 22921765
  46. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Transcranial magnetic stimulation for the treatment of schizophrenia. TEC Assessments. 2011;Volume 26, Tab 6. PMID
  47. Slotema CW, Aleman A, Daskalakis ZJ, et al. Meta-analysis of repetitive transcranial magnetic stimulation in the treatment of auditory verbal hallucinations: Update and effects after one month. Schizophr Res. Dec 2012;142(1-3):40-45. PMID 23031191
  48. Zhang Y, Liang W, Yang S, et al. Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders: A meta-analysis. Neural Regen Res. Oct 5 2013;8(28):2666-2676. PMID 25206578
  49. Rosenberg O, Gersner R, Klein LD, et al. Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study. Ann Gen Psychiatry. 2012;11:13. PMID 22559192
  50. Hao Z, Wang D, Zeng Y, et al. Repetitive transcranial magnetic stimulation for improving function after stroke. Cochrane Database Syst Rev. 2013;5:CD008862. PMID 23728683
  51. Hsu WY, Cheng CH, Liao KK, et al. Effects of repetitive transcranial magnetic stimulation on motor functions in patients with stroke: a meta-analysis. Stroke. Jul 2012;43(7):1849-1857. PMID 22713491
  52. Le Q, Qu Y, Tao Y, et al. Effects of repetitive transcranial magnetic stimulation on hand function recovery and excitability of the motor cortex after stroke: a meta-analysis. Am J Phys Med Rehabil. May 2014;93(5):422-430.PMID 24429509
  53. Jansen JM, Daams JG, Koeter MW, et al. Effects of non-invasive neurostimulation on craving: a meta-analysis.Neurosci Biobehav Rev.  Dec 2013;37(10 Pt 2):2472-2480. PMID 23916527
  54. American Psychiatric Association. Practice Guidelines for the treatment of patients with major depressive disoder. 2010; http://psychiatryonline.org/data/Books/prac/PG_Depression3rdEd.pdf. Accessed February, 2014.
  55. Lefaucheur JP, Andre-Obadia N, Antal A, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. Jun 5 2014. PMID 25034472
  56. National Institute for Health and Care Excellence. Interventional Procedure Guideline (IPG) 214 Transcranial magnetic stimulation for severe depression. 2007; http://publications.nice.org.uk/transcranial-magneticstimulation-for-severe-depression-ipg242. Accessed February, 2014.
  57. National Institute for Health and Care Excellence. Clinical Practice Guideline (CG) 90 Depression in adults: The treatment and management of depression in adults. 2009; http://www.nice.org.uk/guidance/cg90. Accessed February, 2014.
  58. National Institute for Health and Care Excellence. Bipolar disorder: The management of bipolar disorder in adults, children and adolescents, in primary and secondary care. 2006; http://www.nice.org.uk/nicemedia/live/10990/30194/30194.pdf. Accessed April, 2014.
  59. Miyasaki JM, Shannon K, Voon V, et al. Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 66(7):996-1002. [Practice Guideline]. 2006; 2006/04/12:http://www.neurology.org/content/66/7/996.full.pdf+html. Accessed April, 2014.
  60. Kennedy SH, Milev R, Giacobbe P, et al. 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. Oct 2009;117 Suppl 1:S44-53. PMID 19656575 

Codes

Number

Description

CPT 90867 Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; initial, including cortical mapping, motor threshold determination, delivery and management
   90868 Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; subsequent delivery and management, per session
  90869 Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; subsequent motor threshold re-determination with delivery and management
ICD-9 Procedure     
ICD-9 Diagnosis  296.2  Major depressive disorder, single episode
  296.3 Major depressive disorder, recurrent episode
HCPCS     
ICD-10-CM (effective 10/1/15)   Investigational for all relevant diagnoses
  F20.0 - F20.9 Schizophrenia code range
   F33.0 - F33.9 Major depressive disorder, recurrent, code range
ICD-10-PCS (effective 10/1/15)    ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this procedure.
Type of Service  Medicine 
Place of Service  Outpatient 

 


Index

 

Depression, Transcranial Magnetic Stimulation
Magnetic Stimulation, Transcranial
NeoPulse, Transcranial Magnetic Stimulation
NeuroStar, Transcranial Magnetic Stimulation
Transcranial Magnetic Stimulation, Depression
Repetitive Transcranial Magnetic Stimulation, Depression


Policy History

 

Date Action Reason
11/20/01 Add to Medicine section New policy
11/20/01 Replace policy Policy reissued due to a correction to the word electrical in the policy statement. The statement reads: Transcranial electrical stimulation etc., but it should read: Transcranial magnetic stimulation etc. No other changes were made
04/29/03 Replace policy Policy reviewed with literature search; policy statement unchanged
04/16/04 Replace policy Policy reviewed with literature search; policy statement unchanged
3/15/05 Replace policy Policy reviewed with literature search; policy statement unchanged; reference numbers 10–12 added
12/14/05 Replace policy Policy reviewed with literature search; policy statement unchanged; reference numbers 13–15 added. New CPT category III codes for July 2006 added to policy guidelines and code table.
12/12/06 Replace policy Policy reviewed with literature search; reference numbers 15–20 added; title and policy statement modified to include neurologic conditions
12/13/07 Replace policy Policy updated with literature search; references 20-23 added; no change in policy statement.
12/11/08 Replace policy  Policy updated with literature search; rationale revised; reference numbers 24-35 added; no change in policy statement 
12/10/09 Replace policy Policy updated with literature search through October 2009; references 29, 36-38 added; no change in policy statement
01/13/11 Replace policy Policy updated with literature search through October 2010; references 39-41 added; no change in policy statement
1/12/12 Replace policy Policy updated with literature search through November 2011; references added and reordered; 14 older references removed; no change in policy statement
1/20/13 replace policy- coding update only new HCPCS code added
6/12/14 Replace policy Policy updated with literature review through December 11, 2013; references 4, 16, 26, and 59-63 added and reordered; clinical input reviewed; transcranial magnetic stimulation considered medically necessary for treatment-resistant depression under specified conditions
12/11/14 Replace policy Policy updated with literature review through October 30, 2014; references 9, 15, 17, 25, 27, 36, 48, 52-53, and 55 added and some references removed; policy statements unchanged