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Comparison of transcranial magnetic stimulation with electroconvulsive therapy in patients with treatment resistant depression
Major depressive disorder (MDD) is a common mental illness and the leading cause of disability worldwide (Friedrich, 2017). Although multiple pharmacotherapeutic agents are now available to treat MDD, still approximately half of the patients fail to achieve a remission and are labelled as treatment resistant. Treatment resistant depression can be defined as the lack of significant clinical improvement after two adequate trials of two different antidepressants from two different pharmacologic classes (Werremeyer, 2014). In these patients, electroconvulsive therapy (ECT) is efficacious with over 70% remission rate but ECT is accompanied by severe adverse effects that limits its use. The repetitive transcranial magnetic stimulation (TMS) is another FDA approved treatment option for these treatment-resistant patients. Multiple studies have reported its positive safety profile as compared to ECT and detailed guidelines for its use have been published (Rossi et al., 2009).
ECT was first developed in 1938 and has been used as a treatment modality in psychiatry for more than 80 years (Bewernick & Schlaepfer, 2015). It is a procedure that involves induction of a generalized seizure by applying an electrical current to the brain. ECT requires the use of general anesthesia and is often an inpatient procedure. Most patients receive 9 to 12 sessions during the treatment. The minimum charge to induce a seizure is referred to as the seizure threshold. The exact mechanism of action of ECT contributing to the antidepressant effect is still largely unknown, but the seizure induction and the postictal suppression are the most important factors (Bewernick & Schlaepfer, 2015). The average cost of 10 ECT sessions ranges from $10,000 to $15,000 (Cusin & Dougherty, 2012).
Repetitive TMS is a non-invasive procedure that uses series of superficial high intensity electromagnetic pulses, with frequencies ranging from 1 to 20 Hz, to modulate cortical excitability (Rachid, 2018). Significant positive changes were reported in neuronal activity in fronto-limbic regions, in neurotransmission between different regions, and neurotrophic factor concentrations after TMS therapy in patients with MDD (Anderson et al., 2016). TMS can be used as an outpatient and multiple sessions of repetitive TMS are delivered every week. The dorsolateral prefrontal cortex (left, right or bilateral) is often the target of choice and the stimulus intensity varies among the patients and depends upon the patient’s motor threshold i.e. the minimal field intensity needed to produce muscle twitches (Health Quality Ontario, 2016). The average course of TMS ranges from $6,000 to $12,000 (Cusin & Dougherty, 2012).
Multiple systemic reviews and meta-analyses have compared the efficacy of TMS with that of ECT in the treatment of treatment resistant depression. ECT is generally reported to be more effective than repetitive TMS (Chen et al., 2017; Magnezi et al., 2016; Xie et al., 2013) but the ECT is also the least tolerated of all the treatments due to its wide range of adverse effects. Berlim and colleagues (2013) reported in their meta-analysis that the remission rates were 33.6% (38 out of 113 patients) with repetitive TMS and 52% (53 out of 102 patients) with ECT in the patients with treatment-resistant depression. The number needed to treat was 6 (95% CI: 3.2 – 18.9) in favor of ECT. Cognitive impairment and memory loss are the most undesirable adverse effects of ECT. Headache, seizures, muscle pain, oral lacerations, aspiration pneumonia, and the need for anesthesia along with anesthetic side effects are the other main concerns with ECT treatment. The social stigma associated with ECT is also one of the reasons for the intolerance. On the other hand, TMS is generally safe and often causes a mild benign transient headache. TMS may also cause seizure but these seizures are often self-limited and occur rarely with a frequency of less than 0.1%. Unlike ECT, TMS does not cause cognitive impairment and has an added advantage of not requiring anesthesia or need to induce seizure. The main disadvantage with TMS is that only focal and superficial parts of the brain just below the skull are targeted. Without navigation and imaging, the target is missed in one-third of the patients (Bewernick & Schlaepfer, 2015). TMS cannot be used in patients with metal heart valves or prosthetic metal joint replacements.
With the current available data, it can be concluded that ECT is superior to TMS in terms of efficacy, but these comparative studies had certain limitations. First, few of the included studies were non-randomized and control groups were not used. Second, in some studies TMS was used at a relatively lower frequency. Third, both the patients and the examiners in most of these studies were not blind to treatment received resulting in significant bias. Despite the favorable results, ECT is not a popular treatment choice due to adverse effects and social stigma. Therefore, in my humble opinion the TMS should be included in treatment-resistant depression protocols one step ahead of ECT and the ECT should be reserved for those patients who have failed to achieve remission even with TMS therapy.
- Anderson, R. J., Hoy, K. E., Daskalakis, Z. J., & Fitzgerald, P. B. (2016). Repetitive transcranial magnetic stimulation for treatment resistant depression: Re-establishing connections. Clinical Neurophysiology, 127(11), 3394-3405.
- Berlim, M. T., Van den Eynde, F., & Daskalakis, Z. J. (2013). 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. Depression and anxiety, 30(7), 614-623.
- Bewernick, B., & Schlaepfer, T. E. (2015). Update on neuromodulation for treatment-resistant depression. F1000Research, 4.
- Chen, J. J., Zhao, L. B., Liu, Y. Y., Fan, S. H., & Xie, P. (2017). Comparative efficacy and acceptability of electroconvulsive therapy versus repetitive transcranial magnetic stimulation for major depression: a systematic review and multiple-treatments meta-analysis. Behavioural brain research, 320, 30-36.
- Cusin, C., & Dougherty, D. D. (2012). Somatic therapies for treatment-resistant depression: ECT, TMS, VNS, DBS. Biology of Mood & Anxiety Disorders, 2(1), 14.
- Health Quality Ontario. (2016). Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials. Ontario health technology assessment series, 16(5), 1.
- Friedrich, M. J. (2017). Depression is the leading cause of disability around the world. Jama, 317(15), 1517-1517.
- Magnezi, R., Aminov, E., Shmuel, D., Dreifuss, M., & Dannon, P. (2016). comparison between neurostimulation techniques repetitive transcranial magnetic stimulation vs electroconvulsive therapy for the treatment of resistant depression: patient preference and cost-effectiveness. Patient preference and adherence, 10, 1481.
- Rachid, F. (2018). Maintenance repetitive transcranial magnetic stimulation (rTMS) for relapse prevention in with depression: a review. Psychiatry research, 262, 363-372.
- Rossi, S., Hallett, M., Rossini, P. M., Pascual-Leone, A., & Safety of TMS Consensus Group. (2009). Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clinical neurophysiology, 120(12), 2008-2039.
- Werremeyer, A. (2014). Treatment-resistant depression. Mental Health Clinician, 4(5), 211-211.
- Xie, J., Chen, J., & Wei, Q. (2013). Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: a meta-analysis of stimulus parameter effects. Neurological research, 35(10), 1084-1091.
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