1. Aetna considers transcranial magnetic stimulation experimental and investigational for the diagnosis and treatment of major depression, other neuropsychiatric disorders (e.g., schizophrenia, anxiety disorders, panic disorder, and obsessive-compulsive disorder) or any other indications (e.g., chronic pain, migraine headaches, Tourette syndrome, tinnitus, and levodopa-induced dyskinesia) because its value and effectiveness in these roles has not been established.

2. Aetna considers cranial electrical stimulation (also known as electrosleep, electrotherapeutic sleep, cerebral electrotherapy, transcranial electrotherapy, transcerebral electrotherapy, craniofacial electrostimulation, and electric cerebral stimulation as well as the Liss Body Stimulator that is used to treat alcoholism) experimental and investigational for the treatment of neuropsychological indications (alcoholism, chemical dependency, dementia, depression, headaches) or any other indications because its effectiveness has not been established.

Transcranial magnetic stimulation (TMS) is a non-invasive method of induction of a focal current in the brain and transient modulation of the function of the targeted cerebral cortex. This procedure entails placement of an electromagnetic coil on the scalp; high-intensity electrical current is rapidly turned on and off in the coil through the discharge of capacitors. Depending on stimulation parameters (frequency, intensity, pulse duration, stimulation site), repetitive TMS (rTMS) to specific cortical regions can either increase or decrease the excitability of the affected brain structures.

Transcranial magnetic stimulation has been investigated in the treatment of various psychiatric disorders, especially depression. This procedure is usually carried out in an outpatient setting. In contrast to electroconvulsive therapy, TMS does not require anesthesia or analgesia. Furthermore, it does not affect memory and usually does not cause seizures. However, the available peer reviewed medical literature has not established the effectiveness of rTMS in the treatment of major depression or any other psychiatric disorders. More research is needed to ascertain the roles of various stimulation parameters of rTMS for its optimal outcome as well as its long-term effectiveness in the treatment of depression and other psychiatric disorders.

Martin et al (2003) conducted a systematic review of randomized controlled trials that compared rTMS with sham in patients with depression. The authors concluded that current trials are of low quality and provide insufficient evidence to support the use of rTMS in the treatment of depression. This is in accordance with the observations of Fitzgerald and colleagues (2002) who noted that TMS has a considerable role in neuropsychiatric research. It appears to have considerable potential as a therapeutic tool in depression, and perhaps a role in several other disorders, although widespread application requires larger trials and establishment of sustained response, as well as Gershon et al (2003) who stated that TMS shows promise as a novel antidepressant treatment. Systematic and large-scale studies are needed to identify patient populations most likely to benefit and treatment parameters most likely to produce success.

A health technology assessment prepared for the Ontario Ministry of Health and Long-Term Care (2004) concluded: “Due to several serious methodological limitations in the studies (Level 2 -4 evidence) that examined the effectiveness of rTMS in patients with MDD [major depressive disorder], to date, it is not possible to conclude that rTMS is effective or not effective for the treatment of MDD (treatment resistant or not treatment resistant MDD).”

Nemeroff (2007) stated that the role of non-pharmacological therapies such as electroconvulsive therapy, vagus nerve stimulation, deep brain stimulation, and TMS in the treatment of patients with severe depression remain active avenues of investigation.

A randomized clinical trial conducted for the National Coordinating Centre for Health Technology Assessment found that electroconvulsive therapy is a more effective and potentially cost-effective antidepressant treatment than three weeks of rTMS (McLoughlin, et al., 2007).  Forty-six patients with major depression were randomized to receive a 15-day course of rTMS (n = 24) or a course of electroconvulsive therapy (n = 22). One patient was lost to follow-up at end of treatment and another eight at 6 months. The end-of-treatment Hamilton Rating Scale for Depression (HRSD) scores were lower for electroconvulsive therapy (95% confidence interval (CI) 3.40 to 14.05, p = 0.002), with 13 (59%) achieving remission compared with four (17%) in the rTMS group (p = 0.005). However, HRSD scores did not differ between groups at 6 months. Beck Depression Inventory-II (BDI-II), visual analogue mood scales (VAMS), and  Brief Psychiatric Rating Scale (BPRS) scores were lower for electroconvulsive therapy at end of treatment and remained lower after 6 months. Improvement in subjective reports of side-effects following electroconvulsive therapy correlated with antidepressant response. There was no difference between the two groups before or after treatment on global measures of cognition. The NCCHTA study also evaluated the comparative costs of electroconvulsive therapy and rTMS. The investigators reported that, although individual treatment session costs were lower for rTMS than electroconvulsive therapy, the cost for a course of rTMS was not significantly different from that for a course of electroconvulsive therapy as more rTMS sessions were given per course. Service costs were not different between the groups in the subsequent 6 months but informal care costs were significantly higher for the rTMS group (p = 0.04) and contributed substantially to the total cost for this group during the 6-month follow-up period. The investigators reported that there was also no difference in gain in quality adjusted life years (QALYs) for electroconvulsive therapy and rTMS patients. The report noted that analysis of cost-effectiveness acceptability curves demonstrated that rTMS has very low probability of being more cost-effective than electroconsulsive therapy.

The Australian Medical Services Advisory Committee (MSAC, 2007) found insufficient evidence of rTMS to support funding. MSAC considered the safety and effectiveness of rTMS for moderate to severe refractory treatment resistant depression compared to electroconvulsive therapy. MSAC found evidence that rTMS is safe and less invasive than electroconvulsive therapy. However, MSAC also found limited evidence that rTMS may be less effective than electroconvulsive therapy.

There is also a lack of scientific evidence in the use of TMS as a diagnostic tool for psychiatric disorders, and treatment for chronic pain. Pridmore et al (2005) stated that in studies of TMS for the treatment of chronic pain, there is some evidence that temporary relief can be achieved in a proportion of sufferers. Work to this point is encouraging, but systematic assessment of stimulation parameters is necessary if TMS is to attain a role in the treatment of chronic pain. Furthermore, Canavero and Bonicalzi (2005) noted that TMS has no role in the management of patients with central pain, a major chronic pain syndrome.

Funak and colleagues (2006) noted that in healthy volunteers (HV), one session of 1-Hz rTMS over the visual cortex induces dishabituation of visual evoked potentials (VEPs) on average for 30 minutes, while in migraineurs one session of 10-Hz rTMS replaces the abnormal VEP potentiation by a normal habituation for 9 minutes. These investigators examined if repeated rTMS sessions (1-Hz in 8 HV; 10-Hz in 8 migraineurs) on 5 consecutive days can modify VEPs for longer periods. In all eight HV, the 1-Hz rTMS-induced dishabituation increased in duration over consecutive sessions and persisted between several hours (n = 4) and several weeks (n = 4) after the 5th session. In 6 of the 8 migraineurs, the normalization of VEP habituation by 10-Hz rTMS lasted longer after each daily stimulation, but did not exceed several hours after the last session, except in 2 patients, where it persisted for 2 days and 1 week. The authors concluded that daily rTMS can thus induce long-lasting changes in cortical excitability and VEP habituation pattern. However, whether this effect may be useful in preventing migraines remains to be determined.

Wagle-Shukla et al (2007) examined the effectiveness of rTMS for the treatment of patients (n = 6) with levodopa-induced dyskinesias (LID). They reported that a 2-week course of low-frequency rTMS reduced LID as indexed by both objective as well as subjective evaluations, with no change in parkinsonism as evaluated by Unified Parkinson Disease Rating Scale motor scores. The benefit was observed at 1 day after treatment, but not 2 weeks later. The drawbacks of this study were its small sample size and the open labeled design. Furthermore, benefits were not sustained. More research is needed to ascertain the clinical value, if any, of rTMS in the treatment of LID.

In a pilot study, Smith et al (2007) evaluated the effectiveness of rTMS and its effects on attentional deficits and cortical asymmetry in 4 patients with chronic tinnitus using objective and subjective measures and employing an optimization technique refined in our laboratory. Patients received 5 consecutive days of active, low-frequency rTMS or sham treatment (using a 45-degree coil-tilt method) before crossing over. Subjective tinnitus was assessed at baseline, after each treatment, and 4 weeks later. Positron emission tomography/computed tomography (PET/CT) scans were obtained at baseline and immediately after active treatment to examine change in cortical asymmetry. Attentional vigilance was assessed at baseline and after each treatment using a simple reaction time test. All patients had a response to active (but not sham) rTMS, as indicated by their best tinnitus ratings; however, tinnitus returned in all patients by 4 weeks after active treatment. All patients had reduced cortical activity visualized on PET immediately after active rTMS. Mean reaction time improved (p < 0.05) after active but not sham rTMS. The authors concluded that rTMS is a promising treatment modality that can transiently diminish tinnitus in some individuals, but further trials are needed to determine the optimal techniques required to achieve a lasting response. This is in agreement with the findings of Plewnia et al (2007) who reported that the effects of rTMS for patients with chronic tinnitus are only moderate; inter-individual responsiveness varied; and the attenuation of tinnitus appeared to wear off within 2 weeks after the last stimulation session.

Prasko et al (2007) examined if rTMS would facilitate effect of serotonin reuptake inhibitors (SRIs) in patients with panic disorder (n = 15). Patients suffering from panic disorder resistant to SRI therapy were randomly assigned to either active or to sham rTMS. The objective of the study was to compare the 2- and 4-weeks effectiveness of the 10 sessions low-frequency rTMS with sham rTMS add on SRI therapy. These researchers used 1-Hz, 30-min rTMS, 110 % of motor threshold administered over the right dorso-lateral prefrontal cortex (DLPFC). The same time schedule was used for sham administration. Psychopathology was evaluated by means of the rating scales CGI, HAMA, PDSS and BAI before the treatment, immediately after the experimental treatment, and 2 weeks after the experimental treatment by an independent reviewer. Both groups improved during the study period but the treatment effect did not differ between groups in any of the instruments. The authors concluded that low-frequency rTMS administered over the right dorso-lateral prefrontal cortex after 10 sessions did not differ from sham rTMS add on SRIs in patients with panic disorder.

Rossini and Rossi (2007) stated that TMS is widely used in clinical neurophysiology, including rehabilitation and intra-operative monitoring. Single-pulse TMS and other more recent versions (e.g., paired-pulse TMS, rTMS, integration with structural and functional MRI, and neuro-navigation) allow motor output to be mapped precisely to a given body district. Moreover, TMS can be used to assess excitatory/inhibitory intra-cortical circuits and to provide information on brain physiology and pathophysiology of various neuropsychiatric diseases as well as on the mechanisms of brain plasticity and of neuroactive drugs. TMS applied over non-motor areas made it possible to extend research applications in several fields of psychophysiology. Being able to induce relatively long-lasting excitability changes, rTMS has made the treatment of neuropsychiatric diseases linked with brain excitability dysfunctions possible. The authors noted that these uses, however, warrant further large-scale studies. In emerging fields of research, TMS-EEG co-registration is considered a promising approach to evaluate cortico-cortical connectivity and brain reactivity with high temporal resolution. However, safety and ethical limitations of TMS technique need a high level of vigilance.

Transcutaneous electrical nerve stimulation (TENS) is the application of an electrical current through electrodes attached to the skin, and is most commonly used for pain relief. It has also been employed for the treatment of a range of neurological and psychiatric conditions such as alcohol and drug dependence, depression, and headaches. TENS is rarely used for the treatment of dementia. The use of TENS for these indications entails peripherally applied transcutaneous electrical stimulation as well as transcutaneous electrical stimulation applied to the head, also known as cranial electrical stimulation (CES). Although several studies suggested that TENS may produce short-lived improvements in some neurological or psychiatric conditions, the limited data from these studies did not allow definite conclusions on the possible benefits of this intervention.