Mental Health Section - Transcranial Magnetic Stimulation as a Treatment of Depression and Other Psychiatric/Neurologic Disorders

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

DESCRIPTION

Transcranial magnetic stimulation (TMS) is a noninvasive method of brain stimulation. 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 brain. In contrast to electroconvulsive therapy, transcranial magnetic stimulation does not require anesthesia and does not induce convulsions.

The Food and Drug Administration (FDA) granted 510(k) approval for the NeuroStar® TMS Therapy system (Neuronetics, Inc) for the treatment of major depressive disorder in adults who have failed one antidepressant medication.

POLICY/CRITERIA

Transcranial magnetic stimulation of the brain is considered investigational as a treatment for all indications, including but not limited to:

1. Bulimia nervosa (BN)
2. Depression
3. Fibromyalgia
4. Migraine
5. Obsessive compulsive disorder (OCD)
6. Pain
7. Parkinson’s disease
8. Schizophrenia
9. Spasticity
10. Stroke rehabilitation
11. Tinnitus

POSITION STATEMENT

TMS or repetitive TMS (rTMS) has not been established as an effective treatment for any condition.

• Randomized controlled trials comparing active TMS to sham devices are unreliable and do not allow conclusions about true treatment effects.

Effectiveness:

Depression

In a meta-analysis of 16 published trials, a Cochrane review concluded that there was no strong evidence of benefit from TMS when used in the treatment of depression, finding no difference between TMS and sham TMS based on results of the Beck Depression Inventory or Hamilton Depression Rating Scale. (2) In addition, the Cochrane Review found electroconvulsive therapy was more effective than TMS.

Additional meta-analyses of randomized controlled trials exhibited consistent results. (5, 9, 13, 21) Each analysis identified a number of limitations of the included studies such as small patient populations, short study time-lines, confounding co-therapies, and inconsistency with rTMS treatment parameters. The meta-analyses concluded that rTMS indicated some effect when compared to the sham groups, but the clinical significance of this effect and its impact on health outcomes was not demonstrated. The above analyses concluded that additional, larger long-term studies were needed to better define optimal treatment parameters including frequency, positioning, and equipment for rTMS.

The majority of additional randomized controlled trials, that were not included in the Cochrane Review or meta-analyses, also had significant limitations which did not allow conclusions to be made about the effectiveness of TMS as a treatment for depression. Limitations of individual studies and the body of the literature as a whole, include one or more of the following:

• Standardized optimal treatment parameters for rTMS have not been established. Studies varied with respect to frequency, location, intensity, and duration among studies. No study mentioned repeat treatments using rTMS after their intervention phase or in the follow-up assessments. (15, 16, 23-26, 49)
• There were significant or unclear loss to follow-up, greater than 10% per group or 20% total for the study, and poorly defined intention-to-treat (ITT) analyses. (15, 16, 23-26, 30, 47, 49)
• Use of co-therapies such as antidepressants, sham devices in which potential for some therapeutic effect was possible, and mental health counseling were allowed but not quantified in the results, potentially confounding the findings. (15, 16, 23-26, 30, 31)
• Follow-up of all study subjects was over a short period of time, less than 6 months, so durability of the results are unknown. (15, 16, 23-26, 30-32, 47, 48, 49)
• Study populations were small, less than 100 patients total, making results unreliable and difficult to apply to patients requiring treatment in the general population. (15, 16, 23-26, 30-32, 47, 48)
• Randomization methods were not clearly stated or weak methods of randomization were used (e.g. one provider randomly assigned patients to groups using their own personal judgment). (16, 23, 24, 30-32, 48)
• Strict inclusion/exclusion criteria were used which were not representative of patients requiring treatment in the general population, for example,  a mild to moderate level of depression or illness, no comorbidities (or only few that are well controlled), and treatment resistant to standard therapies to name a few. (15, 16, 23, 24, 26, 30, 31, 48)

One large, reliable, double-blind, multicenter study (23 study sites) randomized 325 treatment-resistant depressed patients to daily sessions of high frequency active or sham rTMS. (27) 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, which then become an open-label study. The intent-to-treat analysis showed no significant difference between the active and sham groups in the primary outcome measure, the Montgomery-Asberg Depression Rating Scale (MADRS), and a modest (two point) improvement over sham treatment on the Hamilton Rating Scale for Depression (HRSD). The authors conducted a post-hoc subgroup analysis by eliminating six patients with a higher severity of illness from the study. Following six weeks of treatment the patients in the active rTMS group were more likely to have achieved remission (14% active vs. 5% sham, p=0.038).  These results are not reliable and need to be considered exploratory because the study failed to achieve its primary endpoint. There was no long-term follow-up in this study.

rTMS Compared to Electroconvulsive Therapy (ECT)

From the published studies, no conclusion is possible to indicate that rTMS is better than or as effective as electroconvulsive therapy. A United Kingdom National Institute for Health Research health technology assessment compared efficacy and cost-effectiveness of rTMS and ECT. (28) Forty-six patients who had been referred for ECT were randomized to either ECT (average of 6.3 sessions) or a fifteen day course (five treatments per week) of rTMS of the left dorsolateral prefrontal cortex (DLPFC). ECT resulted in a fourteen point improvement in the Hamilton Depression Rating Scale (HDRS) and a 59% remission rate. rTMS was less effective than ECT (five point improvement in HDRS and a 17% remission rate). Another study reported no significant difference between ECT and rTMS in forty-two patients with treatment-resistant depression; however, response rates for both groups were low. (29) The number of remissions (score of seven or less on the HDRS) totaled three (20%) for ECT and two (10%) for rTMS.

Other Psychiatric: Schizophrenia, Obsessive Compulsive Disorder (OCD), and Bulimia

A number of randomized controlled studies explore the efficacy of TMS for a variety of mental health related disorders other than depression, including schizophrenia, mania, OCD, and bulimia. Studies regarding rTMS as a therapeutic treatment for these diagnoses are still preliminary (feasibility) studies which have a number of limitations that make outcomes unreliable. Some limitations of these studies are:

• Poorly defined or unmet endpoints (33-38)
• Significant or unclear loss to follow-up and poorly defined intention-to-treat (ITT) analyses (17, 35)
• Lack of long-term follow up (17, 18, 33-38)
• Small patient populations (17, 18, 33-38)
• Lack of standardized optimal treatment parameters (17, 18, 33-38)
• Use of co-therapies (17, 18, 33-38)
• Strict inclusion/exclusion criteria which were not representative of patients requiring treatment in the general population (17, 18, 33-38)

A Cochrane review concluded that there was no strong evidence of benefit from rTMS when used in the treatment of OCD, finding no difference between rTMS and sham rTMS based on results of the Yale-Brown Obsessive Compulsive Scale (which is used to measure the severity of OCD) or the Hamilton Depression Rating Scale. A meta analysis was not possible due to the lack of information and poor data available from the three published trials on OCD. (38)

Other Medical Indications

Safety:

All of the randomized controlled trials indicated that rTMS was relatively safe for use. (3-50, 52). No serious adverse safety issues were reported, but some side effects did occur which varied depending on the rTMS parameters that were used in the study.  Some of the side effects included:

• Seizures (rare)
• Pain at stimulation site, face, and skin
• Headaches
• Muscle twitching
• Eye pain
• Toothache
• Stress which lead to thoughts of self harm or mania
• Nausea
• Facial numbness
• Neurocardiogenic syncope

REFERENCES

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 2.01.50
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Cross References

Regence ConsumerTx: Transcranial Magnetic Stimulation

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