The FDA has proposed reclassification of the electroconvulsive therapy (ECT) device for use in treating severe major depressive episode (MDE) associated with major depressive disorder (MDD) or bipolar disorder (BPD) in patients 18 years of age and older. The proposed use would be limited to patients who are treatment-resistant or who require a rapid response due to the severity of their psychiatric or medical condition.
The ECT device is used to induce a major motor seizure in the patient by applying a brief intense electrical current to the patient’s head. Under the proposed order, the device would be reclassified based on the availability of new clinical literature from Class III (highest risk–premarket approval) to Class II (medium risk) with certain special control requirements. The reclassification, however, would not exempt the device from the necessity of filing a premarket notification (510(k)) submission prior to marketing.
In 1979, the FDA decided to classify the ECT device into Class III, rather than Class II, after several Neurological Device Classification Panel members expressed doubt that the characteristics of the device had been identified precisely enough such that special controls could be established providing reasonable assurance of safety and effectiveness (44 FR 51776, September 4, 1979).
In 2009, the FDA opened a public docket to receive information regarding classification of the device (74 FR 46607, September 10, 2009) and received over 3,000 submissions, with the majority of respondents (80 percent) opposing reclassification. The majority of those opposing reclassification cited adverse events from ECT treatment, such as memory loss, brain damage, and death.
The FDA’s review of new clinical literature submitted was summarized in the Executive Summary to the January 27-28, 2011, Neurological Device Panel meeting to discuss ECT classification. The Panel transcript and other meeting materials are available on FDA’s website. Based on this review, FDA concluded that the ECT device demonstrated effectiveness in the acute phase (less than 3 months after treatment).
Panel members, however, indicated that controlled clinical trials are lacking regarding the effectiveness of ECT beyond the acute phase (e.g. long-term effectiveness), in part, due to the fact that many patients have an initial improvement in the depressive symptoms following an acute course of ECT and are able to return to other treatments for managing depression, such as medications and psychotherapy. The FDA examined the results of over 60 randomized controlled clinical trials comparing ECT with either placebo (sham) or antidepressant therapy. The FDA also examined other conditions, including bipolar mania, schizophrenia, schizoaffective disorder, schizophreniform disorder, and catatonia, but there were insufficient clinical data to support effectiveness for these conditions. The ECT device will remain in Class III to be approved for these uses.
The recommended reclassification is limited to patients 18 years of age and older because data on the use of ECT in children and adolescents is limited. Most of the published literature FDA is aware of and reviewed focused on subject populations that did not receive benefit from prior treatments; therefore, the recommended reclassification is limited to treatment resistant populations as well as those patients who require a rapid response due to the severity of their psychiatric or medical condition. Further, practice guidelines published by the American Psychological Association task force on ECT and the National Institute for Health and Clinical Excellence in the United Kingdom recommend that ECT be considered for primary use (i.e., prior to medications) when there is a need for rapid, definitive response due to the severity of a psychiatric or medical condition.
According to the clinical evidence, while medical and physical risks may occur with ECT, they vary in frequency, with the most severe risks being quite rare. Death associated with ECT appears to occur at a very low rate comparable to that of minor surgical procedures. In fact, recent estimates of the mortality rate associated with ECT treatment are one per 10,000 patients or one per 80,000 treatments.
The risks of greatest concern to clinicians and patients remain cognitive and memory impairment. Both the FDA review of literature and the meta-analyses of the randomized controlled studies indicate that while post-procedure disorientation occurs frequently, it is transient, typically resolving within minutes after the procedure is complete.
Several of the risks associated with ECT, including adverse reaction to anesthetic agents/neuromuscular blocking agents, cardiovascular complications, death, and pulmonary complications, are medical/physical risks related to the use of the device. For these risks, safe use of the device is based on appropriate directions for use. FDA believes that labeling provisions are adequate to mitigate these risks.
Finally, the risks of skin burns can be mitigated by performance testing of the device to demonstrate safe electrical performance, adhesive integrity, and physical and chemical stability of the stimulation electrodes.
The FDA has also announced the availability of a draft guidance document entitled “Electroconvulsive Therapy (ECT) Devices for Class II Intended Uses,” that, when finalized, would provide recommendations for 510(k) submissions on how to comply with the special controls. Comments on the proposed order and the draft guidance must be submitted by March 28, 2016.