Cognitive and Memory Impairment of ECT

The next set of slides summarizes the FDA systematic review of the cognitive and memory adverse events literature. For each of these specific cognitive domains, more specific detailed information is available to the Panel if needed.

For time to reorientation, the literature suggests that there’s a longer period of disorientation with bilateral electrode placement and with high dose ECT, although disorientation was generally quite brief. There does not appear to be any evidence of persistent disorientation over the long term. These data will be discussed in more detail by Dr. Krulewitch in her discussion of the meta-analyses conducted by FDA.

For executive function, there is no evidence of significant differences among the various ECT treatment parameters, although there was a single study which suggested greater executive dysfunction with left unilateral ECT compared to right unilateral ECT. Overall, the literature suggests that there is improvement or no statistically significant change from baseline at up to six months after ECT.

For global cognitive function, bilateral electrode placement was associated with greater impairment than right unilateral ECT. There’s no consensus in the literature on change in test performance on the Mini Mental State Examination from baseline up to two weeks following ECT. However, there was an apparent improvement or no change from baseline by three to less than six months. There are no reported effects of energy dose. Again, these meta-analyses of the MMSE conducted by FDA will follow my presentation.

For global memory function, there were no significant differences by energy dose or waveform or with ECT compared to sham, in the medium term, up to three months. There is limited evidence that bilateral ECT typically performed three times a week may be associated with greater global memory impairment. There’s no change from baseline test performance up to six months identified in the literature.

For anterograde memory, I’m going to break it down into verbal and non-verbal memory. For verbal anterograde memory, overall there are inconsistent results in the literature comparing ECT to sham.

However, there does appear to be a greater risk of verbal memory impairment with sine wave compared to brief pulse ECT, bilateral and dominant hemisphere electrode placement, and high energy dose ECT.

With respect to change from baseline, after about one week of treatment, verbal memory function may return to baseline and might improve following right unilateral electrode placement or low moderate energy dose ECT. After about two weeks of treatment, verbal memory functioning following bilateral electrode placement may return to baseline and may actually improve. From three to six months and beyond, there is limited data to determine if verbal memory impairment persists beyond this time period.

I will now turn to anterograde non-verbal memory data. For non-verbal memory function, the literature review yielded the following. ECT is associated with greater impairment compared to sham ECT immediately after treatment. There do not appear to be any differences in non-verbal memory function with respect to electrode placement. Brief pulse ECT may be associated with greater impairment compared to ultrabrief pulse ECT. After about two weeks of ECT treatment, there is no conclusive evidence in the literature to support any differences among the various ECT treatment parameters. However, there is relatively conclusive evidence of no significant changes in non-verbal memory test performance compared to baseline in the short term, which is the two week to three month period. There is limited data to suggest that in the longer term, non-verbal memory deficits may return to baseline levels.

For impersonal retrograde memory impairment, the literature review yielded the following. Immediately post-ECT, bilateral electrode placement may be associated with greater impairment. There are inconsistent findings with respect to electrode placement, pulse, or energy dose from about 24 hours to 3 months post-ECT. There are no differences between sham ECT and ECT, electrode placement, or pulse wave at six months. Detectable changes from baseline are inconsistent up to six months post-ECT. However, again the literature suggests no significant change from baseline appear to be present at six months.