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Electroconvulsive therapy and the diencephalon: A preliminary report
Electroconvulsive Therapy and the Diencephalon: A Preliminary Report Richard Abrams and Michael A. Taylor
N
ONDOMINANT unilateral ECT was introduced in a successful attempt to reduce the amnesia and confusion that accompany classical bilateral ECT. However, unilateral ECT is less effective than bilateral ECT for the treatment of depressed patients,‘.’ an observation that raises theoretical questions regarding the mechanism of action of ECT. Cerebral stimulation sufficient to produce a convulsion is required for effective treatment of depressed patients, and this fact has led to the conclusion that the seizure is the therapeutic agent for ECT.3 But as unilateral and bilateral ECT both yield generalized seizures, variables other than the seizure alone must also influence the therapeutic effectiveness of convulsive therapy. Abrams et al.4 reported that seizures with unilateral ECT were shorter than those with bilateral ECT and less frequently terminated in a period of electrical silence. They postulated that seizures with unilateral ECT were somehow incomplete, in part accounting for the reduced therapeutic effect of this method. Recently, Abrams and Taylor5 treated depressed patients with ECT in which the treatment electrodes were placed bilaterally, but far anterior to the temporal lobes. Therapeutic effects with this method, termed anterior bifrontal ECT, were inferior to those previously obtained with bilateral ECT. The authors suggested that bilateral stimulation of temporal-lobe structures subserving mood and memory systems was, therefore, prerequisite for the fully developed effects of ECT. The present study examines this hypothesis by comparing the effects in depressed patients of electrode placements for ECT that stimulate either one or both temporal lobes yet have the same stimulus parameters and induce seizures of similar pattern and duration. METHOD The study was done in 1 year in a municipal hospital in New York City. Included were all patients referred for ECT who satisfied criteria for endogenous depression.’ Each patient was examined prior to ECT by a research psychiatrist who completed a 15-item depression rating scale’ modified from Hamilton.“ Four to six hours after the fourth ECT, the depression scale was repeated and a global assessment of treatment response made on a scale of severity ranging from 0 (worse) to 4 (recovered). The examining psychiatrist and the patients treated were unaware of which treatment was given. (We also attempted formal memory testing before and after ECT, but most patients were too ill to cooperate fully with pretreatment testing and insufficient data were obtained for analysis.) On the morning of the first treatment session each patient was assigned to one of three treatmentmethod groups. Assignment was made at random by the research nurse using a chance-order series designed to place 10 patients in each group. The treatment.methods were: two nondominant unilateral
From the Department of Psychiatry, New York Medical College, New York, N. Y.. and the Department of Psychiatry, State University of New York, Stony Brook, N. Y. Richard Abrams, M.D.: Assistant Professor of Psychiatry, New York Medical College. Michael A. Taylor, M.D.: Associate Professor of Psychiatry, State University of New York, Stony Brook. Reprints may be obtainedfrom Dr. Abrams, 142 Columbia Heights, Brookl_vn, N. Y. 11201. 01974 by Grune & Stratton, Inc. Comprehensive Psychiatry,
Vol. 15.
No.
3 (May/June), 1974
233
ABRAMS
234
Table
1. Mean Depression-Scale
Scores Before and After
Unilateral Nondominant
Prior to ECT
21.4 ECT:
Absolute
reduction
Percentage
reduction
Global-response
score
7.6 -13.8 -61.68 3.0
ECT for the Three Treatment
TAYLOR
Groups
Unilateral X 2
Nondominant/Dominant
(N= lo)
After fourth
AND
(N= 10)
k6.4)
26.6
(kg.251 k7.39)
7.0 -19.6
k34.3)
-73.4
(k1.25)
3.0
k6.8) (+6.18) (k7.76) k20.08) kO.67)
Bilateral
(N= IO) 24.1 8.0 -16.1 -72.95 3.2
k8.03)
F n.s.
(kg.351
n.s.
(k6.15)
n.s.
k28.43) (+0.92)
n.s. ns.
ECT’s each session spaced 1 min apart; nondominant unilateral ECT followed in 1 min by dominant unilateral ECT each session; one conventional bilateral ECT each session. Treatments were given three times a week, with atropine premeditation and methohexital-succinylcholine anesthesia, to a total of four treatment sessions. Following the fourth ECT session, all patients were given bilateral ECT for the remainder of their therapy. Seizures were induced with the Reiter Mol-AC II apparatus with the treatment button depressed for 2 sec. Generalized seizures were obtained in each case. No psychotropic drugs were given during the study period. When needed to control agitation, sodium amobarbital (250-500 mg intramuscular) was given every 4 to 6 hr. Nighttime sedation with barbiturate or nonbarbiturate sedatives was permitted ad libitum. RESULTS
Thirty patients completed at least four ECT sessions with the same method, and there were 10 in each treatment group. Ages ranged from 23 to 84 years (mean = 48.3), and there were no significant age or sex differences among the groups. Table 1 shows the mean depression-scale scores before and after the fourth ECT, the absolute and percentage reductions in scores after ECT, and the global estimate of treatment response for the three groups. We found no differences among the three treatment groups for the pre-ECT depression-scale scores, the post-ECT scores, the absolute or percentage reductions in depression scores after ECT, or the global estimates of treatment response. Insufficient memory-test data were available for analysis, but the clinical observation of the treating psychiatrist was that no or minimal dysmnesia occurred with two nondominant unilateral ECT’s, that such phenomena were frequently seen with bilateral ECT, and that dominant/nondominant unilateral ECT had an effect on memory somewhere in between the first two methods. DISCUSSION
Two seizures induced each treatment session with consecutive unilateral stimulation of both temporal lobes were no more effective in reducing depression than two seizures induced with unilateral nondominant temporal-lobe stimulation. This observation suggests that bilaterality of temporal-lobe stimulation is not a critical variable for the depression-relieving action of ECT. One seizure each session with conventional bilateral ECT was therapeutically equal to two seizures each session with other methods, and this is consistent with the reported advantage of bilateral over unilateral ECT.‘s2 Bilateral ECT provides simultaneous bitemporal stimulation as well as diffuse passage of current through diencephalic and other axial brain structures. 7,8The path of current flow with unilateral ECT is unknown, but there is evidence from the interseizure EEG,8 from the
ECT AND
235
THE DIENCEPHALON
lack of verbal-memory impairment with nondominant unilateral ECT,‘O and from the lack of visual-memory impairment with dominant unilateral ECT” that cerebral effects of the stimulating current are concentrated under the area of electrode placement. Such currents should not pass directly through diencephalic structures. As neither treatment method using unilateral electrode placement provided simultaneous bitemporal electrical stimulation, it is not possible to assess the relative importance of the simultaneity of bitemporal stimulation versus the direct diencephalic stimulation for the depression-relieving effects of ECT. However, much indirect evidence has been adduced for altered diencephalic functioning in endogenous depression, including the observed changes in sleep/wake cycle, appetite and weight, temperature regulation, secretory patterns, peristalsis, menstrual cycle, and sexual behavior. l2 A specific effect of ECT on diencephalic structures has recently been proposed as a mechanism for its depression-relieving effects,13 and our data provide support for such a hypothesis. It must be determined whether direct diencephalic stimulation is required, or whether it can be provided indirectly through limbic circuits during simultaneous bitemporal stimulation. We are now proceeding with the clinical study of this question in an attempt to separate the effects of these anatomical variables. SUMMARY
In a double-blind controlled study of electroconvulsive therapy (ECT), 30 patients with endogenous depression were randomly assigned to receive one of three treatment methods: two nondominant unilateral ECT’s each session; one nondominant followed by one dominant unilateral ECT each session; one conventional bilateral ECT each session. No differences in therapeutic effect were found among the three treatment methods as measured by depression rating scores obtained before ECT and after the fourth treatment session, or by the rater’s global estimate of treatment response. The possible roles of temporal-lobe and diencephalic stimulation for the depression-relieving effects of ECT are discussed, and the suggestion is made that direct stimulation of the diencephalon is a critical variable for the fully developed therapeutic effect of ECT. REFERENCES 1. Abrams R, Fink M, Dornbush R, et al: Unilateral and bilateral ECT: Effects on depression, memory, and the electroencephalogram. Arch Gen Psychiatry 27:88, 1972 2. Abrams R: Recent clinical studies of ECT. Semin Psychiatry 4:3, 1972 3. Kalinowsky LB, Hippius H: Pharmacological, Convulsive, and Other Somatic Treatments in Psychiatry. New York, Grune & Stratton, 1969 4. Abrams R, Volavka J, Fink M: EEG changes during multiple unilateral and bilateral ECT. Compr Psychiatry 14:25, 1973 5. Abrams R, Taylor M: Anterior bifrontal
ECT: A clinical trial. Br J Psychiatry 122:587, 1973 6. Hamilton M: A rating scale for depression. J Neural Neurosurg Psychiatry 23:56, 1960 7. Hayes KJ: The current path in electric convulsion shock. Arch Neurol Psychiatry 63:102, 1950 8. Smitt JW, Wegener CF: On electric convulsive therapy. Acta Psychiatry Neurol Stand 19:529, 1944 9. Abrams R, Volavka J, Dornbush R, et al: Lateralized EEG changes after unilateral and bilateral electroconvulsive therapy. Dis Nerv Syst [GWAN Suppl] 31:28, 1970
236
10. Dornbush R, Abrams R, Fink M: Memory changes after unilateral and bilateral convulsive therapy (ECT). Br J Psychiatry 119:75, 197 1 II. Cohen BD, Noblin CD, Silverman AJ: Functional asymmetry of the human brain. Science 162:475, 1968
ABRAMS
AND TAYLOR
12. Pollitt JD: Suggestions for a physiological classification of depression. Br J Psychiatry 111:489,1965 13. Carney MWP, Sheffield BF: Electroconvulsive therapy and the diencephalon. Lancet 1:1505, 1973
N
ONDOMINANT unilateral ECT was introduced in a successful attempt to reduce the amnesia and confusion that accompany classical bilateral ECT. However, unilateral ECT is less effective than bilateral ECT for the treatment of depressed patients,‘.’ an observation that raises theoretical questions regarding the mechanism of action of ECT. Cerebral stimulation sufficient to produce a convulsion is required for effective treatment of depressed patients, and this fact has led to the conclusion that the seizure is the therapeutic agent for ECT.3 But as unilateral and bilateral ECT both yield generalized seizures, variables other than the seizure alone must also influence the therapeutic effectiveness of convulsive therapy. Abrams et al.4 reported that seizures with unilateral ECT were shorter than those with bilateral ECT and less frequently terminated in a period of electrical silence. They postulated that seizures with unilateral ECT were somehow incomplete, in part accounting for the reduced therapeutic effect of this method. Recently, Abrams and Taylor5 treated depressed patients with ECT in which the treatment electrodes were placed bilaterally, but far anterior to the temporal lobes. Therapeutic effects with this method, termed anterior bifrontal ECT, were inferior to those previously obtained with bilateral ECT. The authors suggested that bilateral stimulation of temporal-lobe structures subserving mood and memory systems was, therefore, prerequisite for the fully developed effects of ECT. The present study examines this hypothesis by comparing the effects in depressed patients of electrode placements for ECT that stimulate either one or both temporal lobes yet have the same stimulus parameters and induce seizures of similar pattern and duration. METHOD The study was done in 1 year in a municipal hospital in New York City. Included were all patients referred for ECT who satisfied criteria for endogenous depression.’ Each patient was examined prior to ECT by a research psychiatrist who completed a 15-item depression rating scale’ modified from Hamilton.“ Four to six hours after the fourth ECT, the depression scale was repeated and a global assessment of treatment response made on a scale of severity ranging from 0 (worse) to 4 (recovered). The examining psychiatrist and the patients treated were unaware of which treatment was given. (We also attempted formal memory testing before and after ECT, but most patients were too ill to cooperate fully with pretreatment testing and insufficient data were obtained for analysis.) On the morning of the first treatment session each patient was assigned to one of three treatmentmethod groups. Assignment was made at random by the research nurse using a chance-order series designed to place 10 patients in each group. The treatment.methods were: two nondominant unilateral
From the Department of Psychiatry, New York Medical College, New York, N. Y.. and the Department of Psychiatry, State University of New York, Stony Brook, N. Y. Richard Abrams, M.D.: Assistant Professor of Psychiatry, New York Medical College. Michael A. Taylor, M.D.: Associate Professor of Psychiatry, State University of New York, Stony Brook. Reprints may be obtainedfrom Dr. Abrams, 142 Columbia Heights, Brookl_vn, N. Y. 11201. 01974 by Grune & Stratton, Inc. Comprehensive Psychiatry,
Vol. 15.
No.
3 (May/June), 1974
233
ABRAMS
234
Table
1. Mean Depression-Scale
Scores Before and After
Unilateral Nondominant
Prior to ECT
21.4 ECT:
Absolute
reduction
Percentage
reduction
Global-response
score
7.6 -13.8 -61.68 3.0
ECT for the Three Treatment
TAYLOR
Groups
Unilateral X 2
Nondominant/Dominant
(N= lo)
After fourth
AND
(N= 10)
k6.4)
26.6
(kg.251 k7.39)
7.0 -19.6
k34.3)
-73.4
(k1.25)
3.0
k6.8) (+6.18) (k7.76) k20.08) kO.67)
Bilateral
(N= IO) 24.1 8.0 -16.1 -72.95 3.2
k8.03)
F n.s.
(kg.351
n.s.
(k6.15)
n.s.
k28.43) (+0.92)
n.s. ns.
ECT’s each session spaced 1 min apart; nondominant unilateral ECT followed in 1 min by dominant unilateral ECT each session; one conventional bilateral ECT each session. Treatments were given three times a week, with atropine premeditation and methohexital-succinylcholine anesthesia, to a total of four treatment sessions. Following the fourth ECT session, all patients were given bilateral ECT for the remainder of their therapy. Seizures were induced with the Reiter Mol-AC II apparatus with the treatment button depressed for 2 sec. Generalized seizures were obtained in each case. No psychotropic drugs were given during the study period. When needed to control agitation, sodium amobarbital (250-500 mg intramuscular) was given every 4 to 6 hr. Nighttime sedation with barbiturate or nonbarbiturate sedatives was permitted ad libitum. RESULTS
Thirty patients completed at least four ECT sessions with the same method, and there were 10 in each treatment group. Ages ranged from 23 to 84 years (mean = 48.3), and there were no significant age or sex differences among the groups. Table 1 shows the mean depression-scale scores before and after the fourth ECT, the absolute and percentage reductions in scores after ECT, and the global estimate of treatment response for the three groups. We found no differences among the three treatment groups for the pre-ECT depression-scale scores, the post-ECT scores, the absolute or percentage reductions in depression scores after ECT, or the global estimates of treatment response. Insufficient memory-test data were available for analysis, but the clinical observation of the treating psychiatrist was that no or minimal dysmnesia occurred with two nondominant unilateral ECT’s, that such phenomena were frequently seen with bilateral ECT, and that dominant/nondominant unilateral ECT had an effect on memory somewhere in between the first two methods. DISCUSSION
Two seizures induced each treatment session with consecutive unilateral stimulation of both temporal lobes were no more effective in reducing depression than two seizures induced with unilateral nondominant temporal-lobe stimulation. This observation suggests that bilaterality of temporal-lobe stimulation is not a critical variable for the depression-relieving action of ECT. One seizure each session with conventional bilateral ECT was therapeutically equal to two seizures each session with other methods, and this is consistent with the reported advantage of bilateral over unilateral ECT.‘s2 Bilateral ECT provides simultaneous bitemporal stimulation as well as diffuse passage of current through diencephalic and other axial brain structures. 7,8The path of current flow with unilateral ECT is unknown, but there is evidence from the interseizure EEG,8 from the
ECT AND
235
THE DIENCEPHALON
lack of verbal-memory impairment with nondominant unilateral ECT,‘O and from the lack of visual-memory impairment with dominant unilateral ECT” that cerebral effects of the stimulating current are concentrated under the area of electrode placement. Such currents should not pass directly through diencephalic structures. As neither treatment method using unilateral electrode placement provided simultaneous bitemporal electrical stimulation, it is not possible to assess the relative importance of the simultaneity of bitemporal stimulation versus the direct diencephalic stimulation for the depression-relieving effects of ECT. However, much indirect evidence has been adduced for altered diencephalic functioning in endogenous depression, including the observed changes in sleep/wake cycle, appetite and weight, temperature regulation, secretory patterns, peristalsis, menstrual cycle, and sexual behavior. l2 A specific effect of ECT on diencephalic structures has recently been proposed as a mechanism for its depression-relieving effects,13 and our data provide support for such a hypothesis. It must be determined whether direct diencephalic stimulation is required, or whether it can be provided indirectly through limbic circuits during simultaneous bitemporal stimulation. We are now proceeding with the clinical study of this question in an attempt to separate the effects of these anatomical variables. SUMMARY
In a double-blind controlled study of electroconvulsive therapy (ECT), 30 patients with endogenous depression were randomly assigned to receive one of three treatment methods: two nondominant unilateral ECT’s each session; one nondominant followed by one dominant unilateral ECT each session; one conventional bilateral ECT each session. No differences in therapeutic effect were found among the three treatment methods as measured by depression rating scores obtained before ECT and after the fourth treatment session, or by the rater’s global estimate of treatment response. The possible roles of temporal-lobe and diencephalic stimulation for the depression-relieving effects of ECT are discussed, and the suggestion is made that direct stimulation of the diencephalon is a critical variable for the fully developed therapeutic effect of ECT. REFERENCES 1. Abrams R, Fink M, Dornbush R, et al: Unilateral and bilateral ECT: Effects on depression, memory, and the electroencephalogram. Arch Gen Psychiatry 27:88, 1972 2. Abrams R: Recent clinical studies of ECT. Semin Psychiatry 4:3, 1972 3. Kalinowsky LB, Hippius H: Pharmacological, Convulsive, and Other Somatic Treatments in Psychiatry. New York, Grune & Stratton, 1969 4. Abrams R, Volavka J, Fink M: EEG changes during multiple unilateral and bilateral ECT. Compr Psychiatry 14:25, 1973 5. Abrams R, Taylor M: Anterior bifrontal
ECT: A clinical trial. Br J Psychiatry 122:587, 1973 6. Hamilton M: A rating scale for depression. J Neural Neurosurg Psychiatry 23:56, 1960 7. Hayes KJ: The current path in electric convulsion shock. Arch Neurol Psychiatry 63:102, 1950 8. Smitt JW, Wegener CF: On electric convulsive therapy. Acta Psychiatry Neurol Stand 19:529, 1944 9. Abrams R, Volavka J, Dornbush R, et al: Lateralized EEG changes after unilateral and bilateral electroconvulsive therapy. Dis Nerv Syst [GWAN Suppl] 31:28, 1970
236
10. Dornbush R, Abrams R, Fink M: Memory changes after unilateral and bilateral convulsive therapy (ECT). Br J Psychiatry 119:75, 197 1 II. Cohen BD, Noblin CD, Silverman AJ: Functional asymmetry of the human brain. Science 162:475, 1968
ABRAMS
AND TAYLOR
12. Pollitt JD: Suggestions for a physiological classification of depression. Br J Psychiatry 111:489,1965 13. Carney MWP, Sheffield BF: Electroconvulsive therapy and the diencephalon. Lancet 1:1505, 1973