Transcranial magnetic stimulation-based methods in the treatment of depression
- Paul B Fitzgerald
- Aust Prescr 2012;35:59-61
- 1 April 2012
- DOI: 10.18773/austprescr.2012.026
A substantial proportion of patients fail to respond to standard treatments for depression. Several new methods of stimulating the brain are being developed as alternative interventions for these and other patient groups.
Repetitive transcranial magnetic stimulation is a method of brain stimulation that involves the application of repeated magnetic pulses to directly activate cortical neurones. Several studies show it has antidepressant efficacy.
There are few adverse effects of repetitive transcranial magnetic stimulation. However, the optimal stimulation parameters are not yet fully established.
Major depressive disorder is common and disabling with a lifetime prevalence of around 15%.1 There are a range of psychosocial treatments and drugs for depression. Despite these options, approximately 30% of patients remain unwell with ‘treatment-resistant depression’ resulting in substantial suffering as well as high treatment costs.2 The main established treatment option for patients with treatment-resistant depression is electroconvulsive therapy (ECT) but this has cognitive adverse effects, requires general anaesthesia and has a stigma associated with it.3 This has prompted research into new methods of brain stimulation.
Repetitive transcranial magnetic stimulation (rTMS) has recently been developed as an additional option for treatment-resistant depression. It may also have a role for patients who cannot tolerate other treatments.
rTMS involves the application of a rapidly time variable magnetic field, administered via a coil placed over the scalp, to stimulate brain activity4 (see Fig. 1). A high voltage current in the coil generates a focused magnetic field which passes into the brain and induces an electrical field. This induces depolarisation of superficial cortical neurones.4 Repeated high frequency stimulation increases brain activity, and low frequency stimulation decreases it.5 rTMS can be applied either directly to nonconvulsively modulate brain activity or to induce a focused seizure (magnetic seizure therapy).
Fig. 1 Repetitive transcranial magnetic stimulation procedure
|REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION||ELECTROCONVULSIVE THERAPY|
Failure to tolerate other treatments for depression
Possible first-line treatment based on patient choice
Emergency treatment of depression requiring urgent clinical response
|Efficacy||Moderately well established
Response rates <50%
Response rates >50%
|Safety||Low risk of seizure induction
No cognitive adverse effects
No general anaesthetic
|Risks associated with general anaesthesia
Memory impairment, possible other cognitive adverse effects
One of the major benefits of rTMS is its benign adverse effect profile.18 Some patients find the treatment uncomfortable or experience a transient headache afterwards, but there are no other major reported adverse effects. rTMS can induce seizures but the risk is extremely low when treatment is applied following standard safety guidelines.19 The induction of mania is possible in patients with bipolar disorder, but has not been reported in unipolar depression.20
Standard left-sided rTMS clearly has antidepressant properties but there are a range of issues that remain unresolved. These include the optimal method of administration. Other forms of rTMS such as low frequency stimulation applied to the right dorsolateral prefrontal cortex and bilateral rTMS also have efficacy.21 Other uncertainties include the individualisation of treatment parameters and the evaluation of maintenance protocols to limit the problematic issue of depressive relapse. rTMS also appears a useful treatment for patients with relative contraindications to drugs and ECT or when there is a wish to avoid these treatments, such as during pregnancy, but only limited data on such uses are currently available.22
The therapeutic benefits of ECT may be related to the seizure, rather than the direct electrical current. Researchers are investigating the effects of using rTMS to provoke a seizure. This requires rTMS to be applied at a frequency and intensity beyond that used in standard therapy. As with ECT, a general anaesthetic is required.
Several human trials of magnetic seizure therapy have begun but currently insufficient data are available to confirm its place in treatment. Open-label data and a small comparative trial23 have suggested that it might have similar efficacy to ECT with fewer cognitive adverse effects, although this conclusion is still very preliminary.
A range of novel brain stimulation technologies are currently under active investigation for the treatment of depression. rTMS has progressed down this developmental path to a point where it is currently entering into clinical practice. However, further research is still required to optimise its application. Its availability in Australia is currently limited by the lack of a Medicare rebate for treatment. Only limited treatment programs subsidised by hospital services and without direct patient charge are currently accessible in some private and public hospitals. Magnetic seizure therapy is at an earlier stage of development but there are some promising preliminary results.
Professor Fitzgerald is supported by a National Health and Medical Research Council (NHMRC) Fellowship. In the last two years he has received equipment for research from Brainsway Ltd and MagVenture A/S, manufacturers of TMS and related equipment, and Medtronic Ltd. He is also the Chief Investigator on an ongoing NHMRC sponsored clinical trial of magnetic seizure therapy versus ECT, and other rTMS related research studies.
The following statements are either true or false.
1. Unlike electroconvulsive therapy, repetitive transcranial magnetic stimulation therapy does not require a general anaesthetic.
2. Repetitive transcranial magnetic stimulation therapy induces remission in more than 50% of patients with treatment-resistant depression.
Answers to self-test questions
Professor, Monash Alfred Psychiatry Research Centre, The Alfred, Monash University School of Psychology and Psychiatry, Melbourne