STATE UNIVERSITY OF NEW YORK AT STONY BROOK
SCHOOL OF MEDICINE - DEPARTMENT OF PSYCHIATRY
P.O. BOX 457
ST. JAMES, N. Y. 11780
PHONE: 516-444-2929

October 26, 1990

Dockets Management Branch (HFA-305)
Food and Drug Administration
5600 Fishers Lane, Room 4-62
Rockville, MD 20857

Ref: 21 CFR Part 882 Docket # 82P-0316

Gentlemen:

The FDA proposed reclassification of ECT (electroconvulsive therapy) devices to class II is commendable. The restriction in labelling for patients with "Major Depression with Melancholia" is inconsistent, however, with present practice, international experience since 1934, and numerous recent expert reviews, notable that of the Royal College of Psychiatrists of Great Britain in 1989 (1) and the American Psychiatric Association in 1990 (2). Nor is it consistent with the changing diagnostic schemes which are now beginning to view major mental illnesses as varying manifestations of a single endogenous disorder. In the proposed rule and in its in-house Task Force Review of the Literature on ECT. 1982 to 1988, dated June 10, 1988, the FDA failed to fully consider the scientific literature, failed to comprehend the meaning of the studies, and ignored well designed studies, some of which they cited and derogated.

I urge the FDA to recognize that ECT devices, when properly used to induce seizures, are effective for a range of disorders broader than that cited in the rule: ECT is effective for endogenous psychiatric illnesses in which psychosis can occur. In the present classification scheme (DSM-IIIR), these include (but are not limited to) the mood disorders of major depression, bipolar disorder (manic or depressed or mixed phases), with or without psychosis (296.xx); and schizophrenia, catatonic type (295.2x). Since it is highly likely that these labels will be changed in the next few years (DSM-IV is in preparation), a description of the populations suitable for ECT which define the labelling of these devices should be as broad as the prevailing evidence of efficacy and safety allow.

It is often difficult to separate these diagnoses, and many patients exhibit a variety of syndromes in the course of their lifelong illness. It is not unusual for patients to be depressed in one admission, psychotic and depressed in a second, and manic in a third. And these states may or may not be associated by melancholic signs and symptoms. Limiting the use of a treatment to the melancholic phase of an illness as if such a phase is unique is in error and will do a disservice to large numbers of patients.

Others have argued persuasively the merits of ECT in the treatment of a wide range of depressive disorders, notably psychotic depression (3); bipolar disorder with mania (4); and schizophrenia (5). Their arguments have been persuasive for the Task Force of the American Psychiatric Association (2) and the Royal College of Psychiatrists (1). It would be redundant for me to reiterate their persuasive arguments, when the agency staff can read those arguments directly.

I wish to comment on three issues in the recommended rule: the use of ECT in the syndrome of catatonia, in mania, and the recommendations for a sequence in treatment parameters.

Catatonia: When convulsive therapy was developed by Prof. Ladislas Meduna in Budapest in 1934, it was first used (and most successfully) in a patient with catatonia. When the first electrical inductions were made by Professors Ugo Cerletti and Luigi Bini in Rome in 1938, it was for a patient with catatonia. Catatonia is an uncommon psychiatric syndrome, but one which occurs in patients with psychosis (catatonic schizophrenia), in mania and depression (6), and secondary to medical disorders, such as lupus erythematosus and typhoid fever (7). Catatonia is also seen as a manifestations of a toxic reaction to antipsychotic drugs -- the syndrome is known as neuroleptic malignant syndrome. Finally, catatonia has a form known as malignant catatonia, a disorder that is rapidly fatal. In each of these conditions, ECT has been found to be life-saving (8).

For example, in our hospital last year, we were called to treat a young woman with lupus erythematosus who developed a malignant form of catatonia. She was cachectic, was unable to stand or feed herself, and had lost 25% of her body weight. All medical treatments having failed, after five weeks she was treated successfully and rapidly with ECT, and was well in one year follow-up (9).

I recognize that the APA classification schemes, DSM-III and DSM-IIIR do not specifically recognize this syndrome except as a type of schizophrenia (295.2x). Nevertheless, ECT has been life-saving in this syndrome and it is essential that this application be made a feature of labelling (9).

Mania: The syndrome of mania appears in many guises, that of excitement and overactivity, psychosis, psychosis with melancholia, and delirium. It is often thought of as the obverse of depressive mood. In the history of convulsive therapy, manic conditions were identified as suitable for ECT at the same time that depressive states were identified. The development of lithium and its use with antipsychotic drugs replaced the use of ECT for a time -- long enough to determine that therapy resistant and rapid cycling manic patients of may not respond to medication. In such cases, ECT is life-saving. In our recent experience, we have treated two patients in manic delirium who had been continually hospitalized for 2 and for 3 years. Further, a severely manic woman with sickle cell disease, in her second trimester of pregnancy, could not be treated with medication; ECT was highly successful (10).

Treatment Parameters: The FDA proposed rule states that "ECT use should progress from unilateral to bilateral electrode placement and from brief-pulse to sine wave stimulation and from subcritical to minimum amounts of energy needed to induce seizure activity." This recommendation is wholly inconsistent with present practice and with the recommendations of national task forces (1, 2). By making such a recommendation, the FDA is engaging in the practice of medicine, a stipulation from which the agency is clearly enjoined.

The choice of electrode placement is determined by the type of syndrome, medical status, need for urgency in response, and individual psychology and employment. The 1990 APA report does not recommend unilateral placement as the initial choice for all cases; nor does it reserve bilateral placement as a secondary use. It stipulates that each case must be treated individually. In clinical practice, for patients who have concurrent medical illness where each anesthesia exposure must be considered, bilateral electrode placement is clearly preferred. In patients who are severely suicidal, or severely manic (especially where restraints are a consideration), bilateral placement is preferred. For severely catatonic patients, especially if mute and requiring tube-feeding, bilateral placement is preferred. The use of unilateral electrode placements, with their associated 15% response failure rate, is clearly dangerous to these patients (11).

Stimulation currents at subthreshold energy levels are associated with failed or inadequate seizures. Seizures which have been induced at marginal doses of energy are clearly less efficient than those with suprathreshold currents (12), especially when brief-pulse currents and unilateral electrode placements are used (13). Recent research led the two national reviews (1,2) to argue for moderately suprathreshold currents to induce seizures and to monitor seizure duration as an index of treatment efficacy. Comparisons of U.S. experience with fixed dose brief pulse currents with Scandinavian/German experience with variable dose, modified sinusoidal currents finds a greater number of treatment failures in the fixed dose methodology.

Since the definition of an adequate treatment is under active study, the prescription of a defined sequence of treatment parameters is clearly premature and prejudicial to medical practice.

I commend the FDA in seeking to clarify the status of ECT devices, and I urge the agency to simplify the classification and labelling requirements by assigning these devices to Class II. The labelling should be consistent with more than half a century of experience and research, and must include a wider range of endogenous psychiatric illnesses, including the affective illnesses of severe depression and mania, catatonic schizophrenia, and the special syndrome of primary and secondary catatonia.

But the agency should resist interfering in medical practice by seeking to define the technical details of electrode placement, energy level, and current type and dose, leaving these details to the continuing developments of the profession and departures from prevailing practice to case law.

I have been a licensed physician since 1945; certified in neurology in 1952, in psychiatry in 1954, and in psychoanalysis in 1953. I have been a practitioner of ECT since 1952; a researcher in ECT since 1954 with more than 200 publications in convulsive therapy; editor (with Seymour Kety and James McGaugh) of the volume Psychobiology of Convulsive Therapy (Winston/Wiley, New York, 1974); author of the textbook Convulsive Therapy: Theory and Practice (Raven Press, New York, 1979); and Editor-in-Chief of Convulsive Therapy, a quarterly scientific journal published by Raven Press, since its inception in 1985. I have been a Professor of Psychiatry at various medical schools since 1962.

Sincerely yours,

Max Fink, M.D. Professor of Psychiatry

Citations:

1. Royal College of Psychiatrists. The Practical Administration of Electroconvulsive Therapy (ECT). Gaskell, London, 30 pp., 1989.

2. American Psychiatric Association. The Practice of ECT: Recommendations for Treatment. Training and Privileging. American Psychiatric Press, Washington, D.C., 1990.

3. Avery, D. and Lubrano, A.: Depression treated with imipramine and ECT: the DeCarolis study reconsidered. Am. J. Psychiatry 136: 559-62, 1979.

Kantor, S.J. and Glassman, A.H.: Delusional depressions: natural history and response to treatment. Br. J. Psychiatry 131: 351-60, 1977.

Kroessler, D.: Relative efficacy rates for therapies of delusional depression. Convulsive Ther. 1:173-182,1985.

4. Milstein, V., Small, J.G., Klapper, M.H., Small, I.F., and Kellams, J.J.: Uni-versus bilateral ECT in the treatment of mania. Convulsive Ther. 3: 1-9, 1987.

Mukherjee, S., Sackeim, H.A., Lee, C., Prohovnik, I., and Warmflash, V.: ECT in treatment resistant mania. In; C. Shagass et al. (Eds.): Biological Psychiatry 1985. Elsevier, New York, 732-4, 1986.

Berman, E. and Wolpert, E.A.: Intractable manic-depressive psychosis with rapid cycling in an 18-year-old woman successfully treated with electroconvulsive therapy. J.N.M.D. 175: 236-239,1987.