Clinical Memorandum #18
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THE ROYAL AUSTRALIAN AND NEW ZEALAND COLLEGE OF PSYCHIATRISTS Clinical Memorandum #18
TRANSCRANIAL MAGNETIC STIMULATION
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INTRODUCTION Subconvulsive repetitive transcranial magnetic stimulation (rTMS) is being developed as a psychiatric treatment. Its therapeutic potential in psychiatry is being studied in many countries throughout the world, including Australia. It involves the focal application of magnetic energy to the cerebral cortex, inducing small electrical currents which may alter brain functioning with therapeutic effect and without loss of consciousness, loss of memory, or seizure. Research has examined the physiological processes by which rTMS is considered to exert its effects. Reports have generated positive views about its likely efficacy and usefulness in the treatment of Major Depressive Disorder and its use is being researched in other psychiatric conditions (Fitzgerald, Brown, & Daskalakis, 2002).
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EVIDENCE FOR EFFICACY OF rTMS IN DEPRESSION 2.1
Many clinical trials, including sham controlled trials, have been conducted worldwide to assess the antidepressant activity of rTMS. Although treatment protocols have differed with respect to stimulus parameters and site of stimulation, the majority of trials have reported antidepressant efficacy for rTMS, particularly for high frequency rTMS to the left prefrontal cortex. Meta-analyses of these trials have confirmed clear statistical evidence for the superiority of rTMS over a sham control in treating depression, though the magnitude of change in some trials has been of questionable clinical significance (Mitchell & Loo, 2006).
2.2
The efficacy of rTMS in earlier studies may have been compromised by suboptimal treatment paradigms, in particular, limiting the rTMS course to a two-week period. For high frequency left prefrontal stimulation (the form of rTMS for which there is most evidence), recent studies have suggested that extending the treatment course to four to six weeks may be beneficial. In the most definitive trial of rTMS in depression to date, over 300 medication refractory subjects received rTMS or a sham control over a sixweek period, with relatively intense stimulation parameters (intensity and number of stimuli). This study confirmed the superiority of high frequency left prefrontal rTMS over a sham control, but did not produce clinical benefits of greater magnitude than that seen in earlier studies (O’Reardon et al., 2007).
2.3
The optimal rTMS stimulation parameters for efficacy (such as the number, intensity, frequency, and waveform of stimuli, the number and spacing of stimulation sessions, the alteration of parameters over the course of rTMS, and the combinations of stimulation parameters and site) are the subject of ongoing research. In addition, knowledge of predictors of response and patient populations most likely to benefit from rTMS treatment is evolving, with suggestions that older patients, those with psychotic features, and those who are more treatment resistant are less likely to respond to rTMS (Fregni et al, 2005).
Adopted: February 2008 (GC1/08, R39) Currency: Review no later than 3 years after initial approval and each subsequent 3 years.
Clinical Memorandum #18
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SAFETY OF rTMS The safety and side effects of rTMS have been extensively studied. Seizures are not common but may occur, particularly when rTMS is given at high intensity and at high frequencies. Guidelines for safe stimulation parameters have been published (Wassermann, 1998), though seizures may still occur within these stimulation limits (Loo, McFarquhar, & Mitchell, in press). Caution therefore continues to be necessary, with careful screening of subjects for seizure risk factors, and provision for the management of seizures at sites where rTMS is given. The only common side effects are local discomfort at the site of coil application and mild headache. There is no evidence at this stage of any adverse effects on memory or other cognitive functions. Temporary hearing loss is a potential side effect which can usually be prevented by the use of earplugs. There have been reports of the induction of mania in bipolar patients, and a case report suggestive of the induction of delusions (Loo et al., in press).
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INDICATIONS FOR rTMS A thorough psychiatric assessment should be undertaken in order to confirm the diagnosis and identify other comorbid factors. On the basis of currently available data, it can be concluded that rTMS has antidepressant efficacy which may be clinically significant in a subgroup of depressed patients. Further studies are required to explore the question of the robustness of the clinical response, to identify those patients who are most likely to respond, and to optimise stimulation protocols. Given its favourable safety profile, it is reasonable therefore to recommend that rTMS should be available to certain patients in the clinical setting, outside of research, subject to the conditions outlined below (4.1 – 4.5): 4.1
Patients for whom rTMS might be offered outside a research protocol include: a) those suffering from Major Depressive Disorder (DSM-IV-TR) who have failed or who are intolerant of other suitable treatments; and b) previous responders to rTMS who have relapsed.
4.2
In deciding whether to give rTMS to patients with a history of epilepsy or with surgically implanted metal in the head, a careful assessment of specific risk should be made. Relative benefits and risks of rTMS should be considered and discussed with the patient. Additional precautions may also be necessary (for example, adjustment of medications, or consultation with a neurologist).
4.3
In view of the paucity of evidence on the safety of rTMS in pregnancy, pregnant women should not have rTMS outside of a properly conducted and ethically approved clinical trial.
4.4
In view of the paucity of information relating to the use of rTMS in patients under the age of 18, rTMS should only be used outside of an ethically approved clinical trial after careful evaluation of the individual situation by an appropriate child and adolescent psychiatric service.
4.5
Until further data are available, for psychiatric illnesses other than depression, rTMS should only be used within an approved research protocol.
Adopted: February 2008 (GC1/08, R39) Currency: Review no later than 3 years after initial approval and each subsequent 3 years.
Clinical Memorandum #18
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TREATMENT PROCEDURE 5.1
Location and Equipment 5.1.1
Minimum safety equipment The patient having rTMS should be directly observed during stimulation and be appropriately monitored after the procedure, until the responsible clinician has judged that the patient is fit for discharge from the rTMS suite. The following equipment should be within easy access for the conduct of every treatment with rTMS: − oxygen supply; − suction apparatus; − airway tubes, masks and bag for artificial respiration; − intravenous access equipment; and − drugs for the management of seizures. The ready availability of support staff for managing a complication should be ensured. Each practitioner of rTMS should be familiar with the use of this equipment.
5.1.2
rTMS device The device with which rTMS is delivered should be one that is specific for this purpose. It should be approved by local regulatory authorities, serviced and maintained in proper working order, and in accord with the manufacturer’s recommendations. Every rTMS practitioner should have a sound working knowledge of the device.
5.2
Protocol for treatment A written protocol for the conduct of rTMS should be developed. It should specify the following as a minimum: − − − − − − −
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the site(s) of coil placement that will be used and how this will be located on the scalp; the procedure for determining motor threshold, and from this the dose for stimulation; the stimulation parameters and the frequency of treatments; the procedure for protecting against hearing loss; the procedure for managing a seizure; and the frequency of, and the person(s) responsible for, checking the working order of the rTMS device and of the necessary safety equipment; and the conditions under which the stimulation will be varied.
CONSENT FOR rTMS Informed consent should be obtained from the patient by the prescribing psychiatrist. The consent process should detail alternative treatment considerations, the possible benefits of rTMS, the side effects and adverse events, including the possibility of seizures and the induction of mania.
Adopted: February 2008 (GC1/08, R39) Currency: Review no later than 3 years after initial approval and each subsequent 3 years.
Clinical Memorandum #18
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EDUCATION AND TRAINING 7.1
In the treatment of depression and other psychiatric disorders, rTMS is considered to be a medical procedure and should be prescribed by a psychiatrist and administered by appropriately trained clinical staff who are under the supervision of a medical practitioner.
7.2
Those who are intending to administer rTMS should be properly trained in the theory and technique of the treatment and the safe operation of rTMS devices. Training should also include the management of resuscitation and of unexpected complications (for example, a seizure).
QUALITY AND CREDENTIALING 8.1 It is recommended that rTMS should not be an office based procedure. It should be performed in a setting such as a hospital with appropriate trained clinical staff and well maintained rTMS machine and ancillary equipment to support the procedure. 8.2 The protocol for rTMS practice should be approved by an appropriate local body such as a Medical Advisory Committee or Ethics Committee or similar. 8.3 Each institution that conducts rTMS outside a research setting should have in place a formal process which oversees the availability and practice of rTMS, the review of treatments including outcomes and complications, the monitoring of clinical indicators, the training of practitioners, and the establishment of a credentialing practice.
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REFERENCES Eranti, S., Mogg, A., Pluck, G., Landau, S., Purvis, R., Brown, R. G., et al. (2007). A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression. American Journal of Psychiatry, 164, 73-81. Fitzgerald, P., Brown, T., & Daskalakis, Z. (2002). The application of transcranial magnetic stimulation in psychiatry and neurosciences research. Acta Psychiatrica Scandinavica, 105, 324-340. Fregni, F., Marcolin, M., Myczkowski, M., et al. (2005). Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. International Journal of Neuropsychopharmacology, 9, 1-14. Loo, C. K., McFarquhar, T., & Mitchell, P. (in press). A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. International Journal of Neuropsychopharmacology. Martin, J. L. R., Barbanoj-Rodriguez, M., Schlaepfer, T., Clos, S., Perez, V., Kulisevsky, J., & Gironell, A. (2003). Transcranial magnetic stimulation for treating depression (Cochrane Review). In The Cochrane Library, Issue 1, 2003. Oxford: Update Software. Mitchell, P. B., & Loo, C. K. (2006). Transcranial magnetic stimulation for depression. Australian and New Zealand Journal of Psychiatry, 40, 406-413. O’Reardon, J. P., Solvason, H. B., Janicak, P. G., Sampson, S., Isenberg, K. E., Nahas, Z., et al. (2007). Efficacy and safety of transcranial magnetic stimulation therapy in the acute
Adopted: February 2008 (GC1/08, R39) Currency: Review no later than 3 years after initial approval and each subsequent 3 years.
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treatment of major depression: A multi-site randomized controlled trial. Biological Psychiatry (in press, e pub 13 June 2007). Wasserman, E. (1998). Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop in the Safety of Repetitive Transcranial Magnetic Stimulation. Electroencephalography and Clinical Neurophysiology, 108, 1-16.
Adopted: February 2008 (GC1/08, R39) Currency: Review no later than 3 years after initial approval and each subsequent 3 years.
