University of Health Sciences/The Chicago Medical School
Department of Psychiatry and Behavioral Sciences
3333 Green Bay Road
North Chicago, Illinois 60064-3095
Telephone 708.578.3331

October 10, 1990

Dockets Management Branch
FDA
Room 4-62
5600 Fishers Lane
Rockville MD 20857

Re: 21 CFR Part 882 (Docket No. 82P-0316): Neurological devices; proposed rule to reclassify the electroconvulsive therapy device intended for use in treating severe depression

Gentlemen:

I have the following comments concerning the above-referenced
proposed rule, which appeared in the Federal Register, vol. 55,
No. 172, pp. 36578-36590, Wednesday, September 5, 1990.

1. Limitation of intended use to severe depression, as defined by DSM-III-R criteria for major depressive episode with melancholia. (section IV, p. 36580)

a. Exclusion of non-melancholic major depressives.

The 5 references cited in support of this proposed limitation are mostly outdated--4 of them appeared between 1953 and 1965--especially in view of the several random-assignment, double-blind, sham ECT-controlled studies demonstrating the efficacy of ECT in depressed patients who do not meet DSM-III-R criteria for major depressive episode with melancholia, as follows.

Freeman, Basson and Crighton (1978) found genuine ECT (N=20) superior to sham ECT (N=20) in patients suffering from "depressive illness", which the authors defined only as a persistent mood change exceeding customary sadness, accompanied by at least one of the symptoms of guilt, insomnia, retardation, or agitation. This definition is substantially less restrictive than that for DSM-III-R major depressive episode with melancholia, which requires a minimum of 10 depressive features: at least 5 for major depressive episode plus at least 5 more for melancholia.

West (1981) demonstrated the superiority of genuine (N=11) over sham (N=11) ECT in patients with "primary depressive illness" diagnosed according to the Feighner criteria, which are substantially less restrictive than those of DSM-III-R for major depressive episode with melancholia because they require only 5 depressive features for a "definite" or 4 for a "probable" diagnosis.

Brandon et al (1984) found an advantage for genuine (N=38) vs. sham (N=31) ECT in patients described only as having "major depression", without any specification as to endogenicity, psychosis, melancholia, or number or type of symptoms required.

Gregory et al (1985) reported an advantage for genuine (N=40) vs. sham (N=20) ECT in patients who met ICD-9 criteria for major depressive disorder (296.2/3), which are very simply and broadly defined as "a widespread depressed mood of gloom and wretchedness with some degree of anxiety", often with reduced activity or agitation and restlessness, and much less restrictive than DSM-III-R criteria for major depressive episode with melancholia.

Moreover, the FDA's own summary of data in support of the proposed reclassification (section IV para. A, p. 36580) relies heavily on the 1976 study of Avery and Winokur (FDA reference #7) to support the claim that ECT exerts more potent antidepressant effects than tricyclic antidepressants. The Avery and Winokur (1976) study, however, employed only a Feighner "probable" diagnosis of depression--that is, at least four depressive symptoms--which is far less restrictive than DSM-III-R requirements for a major depressive episode with melancholia.

Thus, the proposed rule to limit the use of ECT devices in the treatment of major depression to patients who meet DSM-III-R criteria for major depressive episode with melancholia is unjustifiably restrictive, and should be broadened by dropping the "with melancholia" qualifier.

b. Exclusion of patients with schizophrenia.

The FDA's position (p. 36582) that the evidence regarding the efficacy of ECT in schizophrenia is inconclusive because it is based on mainly anecdotal and uncontrolled studies omits consideration of two important double-blind, random assignment, sham-ECT controlled studies:

Bagadia et al (1983) found a course of 6 genuine ECTs plus placebo (N=20) to be therapeutically equal to a course of 6 sham ECTs plus 600 mg/day chlorpromazine (N=18) in a sample of 38 patients who met the stringent Research Diagnostic Criteria for schizophrenia. This study is notable for excluding patients with prominent affective symptoms.

Brandon et al (1985) found a course of 8 genuine ECTs (N=9) significantly more effective than 8 sham ECTs (N=8) in lowering Montgomery-Asherg Schizophrenia Scale scores in a sample of 17 patients diagnosed as schizophrenic according to the PSE-based CATEGO program.

Taken together with the Taylor and Fleminger (1980) sham-ECT controlled study cited by the FDA, these reports provide strong scientific evidence for the efficacy of ECT in schizophrenia.