Inefficacy of Burst-Suppression Anesthesia in Medication-Resistant Major Depression: A Controlled Trial

Abstract

Burst-suppression anesthesia (BSA) has been previously compared with electroconvulsive therapy (ECT) in drug-resistant depression, with promising results. We have carried out a double-blind randomized clinical trial comparing BSA with sham-BSA in 20 patients meeting DSM-IV criteria for major depression with inadequate response to antidepressant drugs and who chose BSA as an alternative to ECT. After withdrawing antidepressant drugs, patients were randomized to receive four sessions of either BSA (induction with propofol followed by the anesthetic agent sevoflurane, achieving BSA for 1 hour) or sham-BSA (induction with propofol until loss of consciousness, followed by spontaneous awakening in 5-10 minutes). Decrease in the Hamilton Rating Depression Scale was larger with BSA (-6.0 +/- 7.3) than with sham-BSA (-2.5 +/- 4.5), but differences did not reach statistical significance ( t = -1.08, p = 0.3). In our sample, we have not found BSA to be superior to sham-BSA and therefore cannot consider BSA as an alternative to ECT.

Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression

“…The explanation for why our results were more positive than other later studies may be due to closer adherence to the original protocols, particularly in patient age, dose/duration of each ISO session, and use of more ISO treatment sessions. As suggested by the QIDS-SR16 self-report data in Figure 2, much of the beneficial effect of ISO occurred in sessions 5–10, while Garcia-Toro et al terminated their treatments after only 4 sessions, and they used sevoflurane which might be less effective than ISO, especially if sustained EEG burst suppression is needed for a clinical benefit [14]. We also restricted our sample to persons aged 65 and younger, in part because of the increased likelihood of adverse blood pressure and cardiovascular concerns in elderly patients, like those studied by Greenberg et al [13].…”

“…In contrast, however, Greenberg, et al [13] showed relatively little improvement with ISO treatments in a pilot study involving 6 elderly depressed patients (including 5 aged 74–82 years). In another pilot study, Garcia-Toro, et al [14] treated 10 patients with 4 treatments of low dose sevoflurane (approximately 2.5%). While a 24% reduction in depressive symptoms was noted on average, the clinical effect was not deemed sufficient after 4 treatments and patients were switched to ECT.…”

The Clinical Utility of Inhalational Anesthesia With Sevoflurane in Electroconvulsive Therapy

“…13 This technique is described in the European literature and has not been used with any degree of regularity in the United States. A thorough discussion of the safety and efficacy issues with burst suppression therapy is beyond the scope of this report, but suffice it to say that it represents a different procedure from using brief inhalational anesthesia for ECT.…”

Leukocyte Gene Expression in Patients with Medication Refractory Depression before and after Treatment with ECT or Isoflurane Anesthesia: A Pilot Study

“…Positive antidepressant effects of High ISO were reported by Carl et al [11] and Engelhardt et al [12]. In contrast, Greenberg et al [13] reported little improvement with High ISO treatments in 6 elderly depressed patients, and García-Toro et al [14] found only limited improvement after 4 prolonged treatments of low dose sevoflurane (24% reduction in depressive symptoms).…”

“…We suggested that the previous unsuccessful studies used too few treatments when, indeed, even the gold standard intervention, ECT, requires 8–12 treatments for maximal effectiveness. Also, we hypothesized that anesthetic treatment at doses that are too low to produce strong cortical BS (like the sevoflurane dose used by García-Toro et al [14]) would have minimal antidepressant effects. Thus, we compared responses of 8 patients with medication refractory depression treated with 10 sessions of High ISO with confirmed BS to 20 patients treated with bifrontal ECT.…”