Effective replacements for convulsive therapy have long been sought, and many methods have been tried. In the past decade, interest has focused on transcranial magnetic stimulation (TMS), vagus nerve stimulation, and deep brain stimulation as alternatives to electroconvulsive therapy (ECT) for patients with depressive mood disorders.1,2 The verdict for TMS is now in, finding it of very limited benefit and not a replacement for ECT.
A sham TMS and active TMS multisite comparison carried out by national experts screened 860 outpatients to enroll 190 antidepressant-drug-free patients with unipolar nonpsychotic major depressive disorder.3 The patients were randomized, 92 patients receiving active and 98 receiving sham TMS. Baseline Hamilton Rating Scale for Depression (HAM-D) scores averaged modest severity degrees of illness, 26.3 and 26.5, respectively, with comparable Montgomery-Åsberg Depression Rating Scale values. Of the TMS group, 13 of 92 remitted on HAM-D and Montgomery-Åsberg Depression Rating Scale ratings, whereas 5 of 98 did so with sham TMS. The authors emphasize and are gratified with the difference (statistically at ≤0.02) and hail the antidepressant activity of TMS. But when we define the remission rates of 14% and 5%, the effective assessments are of very limited clinical significance.
A direct comparison of TMS and ECT was carried out in the United Kingdom.4 Of 46 patients with major depression referred for ECT, 24 were randomly assigned to a 15-day course of TMS, and 22 to a standard course of ECT. Using HAM-D scores, 13 (59.1%) of 24 patients remitted with ECT, and 4 (16.7%) of 24 remitted with TMS. The TMS treatment was optimized, but half the ECT patients were treated with right unilateral electrode placement with dosing established at 2.5 times the calibrated seizure threshold. This form of ECT is significantly less effective than standard bilateral ECT, and despite this handicap, the efficacy of ECT clearly exceeded that of TMS by almost 4-fold.
The efficacy of all ECT and TMS comparisons is summarized by Rasmussen,5 citing overall response rates of 38% for TMS compared with ECT rates of 58.8%. The latter rates are markedly inferior to the remission rates averaging 80% in the 2 large CORE studies.6,7 The cost of TMS as presently charged at the Mayo Clinic is greater than that for a course of ECT, and he properly questions the ethics of recommending TMS in medication treatment failures, indicating the necessity to warn patients of the limited efficacy of TMS.
Transcranial magnetic stimulation is a commercially developed technology initially designed to stimulate the motor pathways of patients with motor paralysis secondary to brain lesions. Localized pulsating magnetic fields stimulate brain neurons, sending currents to motor end plates eliciting motor responses to maintain motor strength and substance. The support for the study of TMS in depressed patients comes mainly from the device manufacturers and not from theoretical or experiential evidence. The markets for the applications in brain-damaged subjects being small, manufacturers sought clinical trials in more common disorders, with a special emphasis on the very large populations of patients with major depression failing relief by conventional antidepressant treatments. An additional justification comes from the superficial similarity of the electric currents in ECT and the physical equivalence of electricity and magnetism, as demonstrated early in electricity history by Michael Faraday's generator.
The choice of major depression is also encouraged by the oft-cited mantra that ECT induces memory loss, sometimes severe and occasionally permanent, and the fancied expectation that brain stimulation without seizures would achieve antidepressant efficacy without effects on cognition. The unsound hope for lesser effects on cognition and memory by targeted magnetic stimulation is used to justify neurostimulation trials.1,2
This enthusiasm disregards the unique feature of convulsive therapy, that of seizure induction. Attempts to replace the seizure have preoccupied researchers for decades, and all previous attempts have failed. Would the electrical stimulus alone elicit the same benefits? Sham ECT was tested against real ECT, and in an experiment in 1957, 51 patients were randomly assigned to either real or sham ECT.8 Of the 24 patients treated with ECT, 17 were discharged as recovered or improved; of the sham-treated patients, only 4 were discharged. When 19 of the sham-treated patients were then treated with ECT, 16 were discharged. (At the time, patients with manic-depressive illness and schizophrenia were lumped together and treated with the same courses of ECT.) Similar results are reported in other sham ECT studies.9 Two decades later, the British Medical Research Council-supported studies again assessed sham ECT, finding the seizure essential to efficacy.10
Many other alternatives for ECT have been recommended and tested. Seizure inductions were first made with the intravenous administration of camphor and then pentylenetetrazole. Electrical inductions (ECT) were found to be as effective, more facile, less expensive, and with lesser risks than chemical inductions and quickly became the principal induction method. Although direct comparisons were few, the facility, ease of use, and lesser expense of ECT led to the abandonment of chemical inductions. When an inhalant flurothyl was suggested as a replacement for ECT in 1959, randomized controlled trials found it and ECT equivalent in efficacy and adverse effects, but the inhalant technique was clumsy, difficult, and expensive, and ECT retained its primary role.8 Electrosleep, electroencephalogram α enhancement, bifrontal direct currents, and isoflurane anesthesia-induced electroencephalogram silence were other nonseizure methods suggested, tested, and discarded as ineffective. Transcranial magnetic stimulation, vagus nerve stimulation, and deep brain stimulation are the latest suggested replacements for ECT.
The efficacy of optimized ECT is not challenged by TMS. Electroconvulsive therapy is most effective in the relief of psychotic depression, catatonia, and delirious mania, and no neurostimulation method challenges this dominance. The question today is not to seek a replacement through neurostimulation but to seek an understanding of the mechanism of ECT. How do seizures restore impaired moods and thoughts? By understanding the mechanism, it should be possible to replace ECT, perhaps by an effective intervention with less optic dissonance and lesser adverse effects.
1. George MS, Belmaker RH, ed. Transcranial Magnetic Stimulation in Neuropsychiatry
. Washington, DC: American Psychiatric Press, Inc; 2000.
2. Lisanby SH, ed. Brain Stimulation in Psychiatric Treatment
. Washington, DC: American Psychiatric Press, Inc; 2004.
3. George MS, Lisanby Sh, Avery D, et al. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder. A sham-controlled randomized trial. Arch Gen Psychiatry
4. Eranti S, Mogg A, Pluck G, et al. A randomized controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression. Am J Psychiatry
5. Rasmussen K. Some considerations in choosing electroconvulsive therapy versus transcranial magnetic stimulation for depression. J ECT
6. Kellner CH, Knapp RG, Petrides G, et al. Continuation ECT versus pharmacotherapy for relapse prevention in major depression: a multi-site study from CORE. Arch Gen Psychiatry
7. Kellner CH, Knapp R, Husain M, et al. Comparing bifrontal, bitemporal, and right unilateral electrode placement in ECT: a multisite study from CORE. Br J Psychiatry
8. Fink M. Convulsive Therapy: Theory and Practice
. New York: Raven Press; 1979.
9. Ulett GA, Smith K, Gleser GC. Evaluation of convulsive and subconvulsive shock therapies utilizing a control group. Am J Psychiatry
10. Palmer RL. Electroconvulsive Therapy: An Appraisal
. New York: Oxford University Press; 1981.