Cognitive and Memory Problems with ECT

A second area of key risks associated with ECT use is cognitive and memory dysfunction. The FDA review found that ECT is likely associated with immediate general cognitive and memory dysfunction. Cognitive dysfunction is represented by disorientation. Disorientation appears to be transient and generally resolves in a matter of minutes after the procedure.

Memory dysfunction in general largely resolves in the days to weeks after the completion of a course of ECT. However, in certain domains, particularly in anterograde verbal memory and retrograde autobiographical memory, deficits may be more prominent and/or persistent. While anterograde memory deficits may resolve in the days to weeks after ECT, autobiographical memory deficits may be more persistent. Per Dr. Como’s and Dr. Krulewitch’s presentations, at one to two weeks post-ECT, there is evidence that suggests that autobiographical memory performance is approximately 76 to 77 percent of baseline performance for right unilateral treatment and 58 to 67 percent for bilateral treatment. Limited evidence suggests that ECT memory deficits may approach baseline at six months.

In terms of mitigating factors, studies have demonstrated that potential mitigating factors for reducing the occurrence and risk of memory and cognitive adverse events might include exclusive use of square wave, direct current, brief pulse stimulus, use of ultrabrief pulse, 0.3 milliseconds stimulus, exclusive use of unilateral nondominant electrode placement, use of bifrontal electrode placement, or limiting ECT administration to twice per week.

When the onset of memory and cognitive function are noted during the course of ECT, other mitigating strategies may include switching from bilateral to unilateral treatments, decreasing energy dose or employing ultrabrief pulse stimulus. Identification of safe stimulation parameters in the device labeling to inform practitioners of safe device use may serve as an additional mitigating factor.

Please keep this discussion in mind in your deliberations of the following Panel question regarding mitigating the risks of adverse cognitive and memory adverse events, by employing physician labeling recommendations for exclusive use of brief pulse, that is 1 to 1.5 millisecond waveform stimulus; use of ultrabrief pulse, 0.3 millisecond stimulus; exclusive use of unilateral nondominant electrode placement; use of bifrontal electrode placement; limiting frequency of treatment to a maximum of twice weekly during a course of ECT; and monitoring cognitive status prior to ECT and throughout the course of treatment.

Also patient labeling requiring the use of a checklist of all known risks of ECT, with each item to be signed off by both patient and physician prior to initiating treatment or requirement of further premarket studies, either preclinical, bench or animal testing, or clinical studies for significant changes in device technology or new indications for use.

Please discuss each of these potential controls and whether it, either alone or in combination with others, adequate mitigates the cognitive and memory risks of ECT.

ECT Device Malfunction

My only device malfunction was identified as the third category of key risks of ECT devices. The proper functioning of all devices, not only ECT devices, is typically mitigated by generally accepted manufacturing and safety standards. These include general controls, such as good manufacturing practices and quality system regulations as described in the Code of Federal Regulations, as well as through adherence in international safety standards of medical devices such as the International Electrotechnical Commission, for example, IEC 60601-1-1 for medical electrical system safety requirements, and electromagnetic compatibility.

In summary, the objective of this Panel meeting is to gain expert recommendations on the question of whether ECT devices should be classified as Class II or Class III for each of the currently cleared indications. To review the classifications, Class II devices cannot be classified into Class I because general controls themselves are insufficient to provide reasonable assurance of the safety and effectiveness of the device, and there’s sufficient information to establish special controls to provide such assurance. Class III devices are those for which general and special controls cannot be established and therefore provide reasonable assurance of the safety and effectiveness of the device, and therefore premarket approval is required.