Movement Disorders Vol. 6 , No. 4, 1991, pp. 293-303 0 1991 Movement Disorder Society
Review
Electroconvulsive Therapy in Parkinson’s Disease and Other Movement Disorders *Raymond Faber and ?Michael R. Trimble *Department of Psychiatry, University of Texas Health Science Center at San Antonio and Audie L . Murphy Memorial Veterans Hospital, San Antonio, Texas, U . S . A . ,and ?National Hospitals and Institute of Neurology, Queen Square, London, England
Summary: Early case reports note marked improvements in the signs of Parkinson’s disease (PD) in several patients with coexisting psychiatric disorders after treatment with electroconvulsive therapy (ECT). Studies since 1959 reveal improvement of parkinsonism in over half of PD patients receiving ECT, regardless of the presence or absence of psychiatric comorbidity. Druginduced parkinsonism, tardive dystonia, and tardive dyskinesia have also been shown to improve with ECT administration; tic syndromes have achieved mixed results. In animals, ECT enhances dopamine-mediated effects and increases GABA concentrations in the CNS. Optimal parameters relevant to the antiparkinsonism effects of ECT require further study. Key Words: Electroconvulsive therapy-Movement disorders-Parkinson’s disease.
that the case descriptions were submitted for publication. There have been six reports on the result of ECT on PD without psychiatric comorbidity. One of these was a single case report; four were open studies of consecutive PD patients given ECT for severe, usually “on-off,” symptomatology , and one recent study used a double-blind methodology with sham ECT as a control. We have divided the literature into case reports and continuous series with psychiatric comorbidity, and continuous series and studies without psychiatric comorbidity. The less extensive and more ambiguous literature on ECT in some other movement disorders is also summarized.
i n this review, the literature on the effects of electroconvulsive therapy (ECT) on the motor disabilities of Parkinson’s disease (PD) and other movement disorders is examined. The available data are not widely appreciated but do lead to the conclusion that there is a role for ECT in the management of some cases of PD. Beginning with the observations of Gallinek in 1947 (I), there have been 35 reports on PD and ECT. Modern studies beginning with Fromm in 1959 (2) include 14 single case reports, while another seven have been case reports on from two to seven patients. These account for 33 separate patients, all of whom had a coexisting psychiatric condition that was the indication for the administration of ECT. It is notable that in these instances, the results of ECT on PD signs were often so marked
PD WITH PSYCHIATRIC COMORBIDITY Early History
Address correspondence and reprint requests to Dr. R. Faber, Department of Psychiatry, Audie L. Murphy Memorial Veterans Hospital, 7400 Merton Minter Drive, San Antonio, TX 78284, U.S.A.
Eight reports from the 1940s and 1950s, which mainly pertained to the safe administration of ECT
293
294
R . FABER AND M . R. TRIMBLE
to geriatric and medically ill patients, include mention of over 20 parkinsonian patients, some of whom had significant improvements in their motor disabilities. Kalinowsky (3) described improvement in both parkinsonian symptoms of 7 years’ duration and depression in a 68-year-old woman given six ECT treatments. Since this case was prototypical, we will translate and quote it in some detail. Twelve years ago, Y, a 68-year-old woman, had a psychotic episode with delusions of persecution which lasted for several months. Seven years ago she began showing symptoms of Parkinson’s disease. Her face became expressionless and her movements became slowed. A few weeks prior to her first hospitalization in the Neurological Institute in July 1945, she showed psychological changes and at the same time became totally immobile. At admission she presented the typical picture of severe parkinsonism. Psychiatrically hallucinations and delusions predominated; she believed herself to be in prison, heard the voices of police officers and was in a state of constant fear and agitation. She received 6 electroshock treatments during which the psychotic picture abated completely. Simultaneously with the psychiatric improvement, the stiffness of the various muscle groups receded to such an extent that the patient could not only walk at discharge, but was capable of total self care, although she retained symptoms of parkinsonism such as mask facies, lack of associated movements and moderate rigidity. One year later, in August 1946, she again suffered a depression with delusions. Again she became totally immobile during that episode. The psychosis resolved after 5 ECTs and her ability to walk returned after 3 treatments.
Negative findings were also reported, however, by Kaplan and Freund (4), who treated four patients with parkinsonism and mental changes and noted no effects on any parkinsonian symptoms. Savitsky and Karliner (5) described the effects of ECT on seven patients with PD and depression. In four of these seven parkinsonism was unchanged, two patients had remission of tremor though rigidity persisted, while another patient had improvement of both tremor and rigidity. Shapiro and Goldberg (6) treated three patients with depression and PD with ECT and described improvement of parkinsonian signs in one. Between 1947-55 there were four publications concerning the safe administration of ECT to geriatric and medically ill patients with coexisting psychiatric disorders. Gallinek (1) described a 64-yearold woman with a 3-year history of PD. Eight ECT
Movement Disorders, Vul. 6, No. 4, 1991
treatments induced a remission of her depression while her parkinsonism was unchanged. In three separate series, each including over 100 participants (7-9), several patients with PD safely received ECT with no mention made of any change in neurologic status. Modern Reports We have listed all 27 modern reports on PD and ECT in Table 1 . Lebensohn and Jenkins (10) described “marked improvement” in each of two patients after four sessions of ECT. One patient had mainly rigidity; the other had prominent rigidity and tremor. In both, the improvement lasted for “many months.” Lipper and Bermanzohn (1 1) described a 54-yearold man with PD who, after seven ECT sessions for psychotic depression, regained “good control” with the reinstitution of his prior L-dopa dose. No unique benefits were ascribed to his ECT. In a letter, Brown (12) reported a “poorer than usual” antidepressant effect in seven PD patients, each given one to four courses of eight ECT treatments per course. He makes no mention of any improvement in PD symptoms. Of note, however, was the fact that all seven of his patients showed moderate to severe dementia before ECT was given. In three patients described by Lebensohn (13), one evidenced “striking improvement,” one “moderate improvement,” and the other little improvement in parkinsonian symptoms while being treated for depression. Rainey and Faust (14) claimed that three ECT courses over 3 years reduced and temporarily relieved signs of parkinsonism in a delusionally depressed man who had also intermittently received neuroleptic medication but whose diagnosis by a neurologist was primary parkinsonism. Dysken et al. (15) described in great detail a 69year-old man with PD who received 12 bilateral ECT treatments for depression. A partially blinded rater used a formal rating scale to document substantial improvement in rigidity and bradykinesia with no alteration in tremor. Asnis (16) treated a 61-year-old man with depression and PD with six bilateral ECT treatments, obtaining an excellent antidepressant response and marked overall improvement in PD symptoms evaluated by rating scales. However, when the patient was observed 7 weeks after treatment, both depressive and parkinsonian symptoms had returned to pre-ECT baseline levels. Barcia and Martinez (17) described a 70-year-old man with both depression and PD that “disap-
ECT IN PARKINSON’S DISEASE
295
TABLE 1. Electroconvulsive therapy (ECT) effects on Parkinson’s diseuse (CPD) ~~
No. of Study
Patient history
patients
Psychiatric morbidity
ECT parameters
~
Response duration
Results on PD
Parkinsonism with psychiatric comorbidity Lebensohn and Jenkins (10) (1975)
2
Lipper and Bermanzohn (1 I ) (1975)
I
Brown (12) (1975)
7
Lebensohn (13) (1975)
3
Rainey and Faust (14) (1975)
1
Dysken et al. (IS) (1976)
1
Asnis (16) (1977)
4 treatments
PD 7 yr
Psychotic depression and bipolar depression, respectivefy Psychotic depression
Average age 67, all moderately to severelv demented NS
Depression, obtained “poorer than usual” ECT antidepressant response Depression
1-4 courses, 8 sessions per course
65 yr old, no L-dopa, prior neuroleptic exposure 69 yr old. prior treatment with thioridazine
Depression
3 courses over 3 yr
Depression
12 bilateral
1
61 yr old, 4 yr PD,
Depression
6 bilateral
Barcia and Martinez (17) ( I 978) Yudofsky (18) (1979)
1
prior L-dopa 70 yr old
Depression
3 ECT
1
66 yr old, 2 yr PD, prior r-dopa
Delusional depression
10 ECT
Ward et al. (32) (1980)
1
57 yr old, 10 yr PD, on r-dopa
Psychotic depression
3 courses of
Levy et al. (19) (1983)
1
76 yr old, PD 18 yr, on L-dopa
Depression
10 ECT
Holcomb et al. (20) (1983)
1
72 yr old, concurrent TD
Delusional depression
14 bilateral
Young et al. (21) (1985)
1
Marked improvement
1
Depression unrelieved by ECT, dementia also present Depression
7 unilateral
Raskin (22) ( 1985)
73 yr old, “on-off ’ several yr NS
NS
Marked improvement
Baruch et al. (23) (198s) Jaeckle and Dilsaver (24) ( 1986) Burke et al. (25) (1988)
6
NS
Depression
4 of 6 improved
1
59 yr old
Bipolar psychotic depression
7-15 ECT treatments 9 bilateral
Sustained with maintenance ECT 3-8 yr
Marked improvement
NS
3
Average age 71
Depression
5 unilateral
Much improved
Over I mo
72 yr old
6 unilateral 8 unilateral 12 bilateral
Marked improvement No change Marked improvement
12 days
1
Depression Depression Mania
2
Average age 63
Psychosis secondary to L-dopa and bromocriptine in both patients
6 bilateral
Rating scales used, moderate improvement
Over 6 mo
3 bilateral
Rating scales used, moderate improvement
Over 5 mo
Atre-Vdidya and Jampala (26) (1988) Hurwitz et al. (27) (1988)
Pre-L-dopa
each 7 treatments
NS
bilateral ECT
Marked improvement both in patient with mainly rigidity and patient with rigidity and tremor No unique benefit from ECT, “good control” with reinstitution of prior L-dopa dose No comment on PD symptoms One striking improvement, one moderate improvement, one little improvement PD signs reduced and temporarily relieved
Many months in both
NS
NS
NS NS
Bradykmesia and rigidity, greatly improved, tremor not affected, rating scale used Marked overall improvement, rating scales used Marked improvement
NS
Marked improvement in gait, speed, stability, rigidity, self-care; rating scale used Significant improvement with courses I and 2 ECT
3 days
Substantial improvement in gait, stability, speed, rigidity Rating scales used; PD marked improvement, TD markedly worse
Relapsed within 7 wk NS
Return of initial PD symptoms in spite of maintenance ECT Over 6 mo 1 wk, then no
significant PD with 2nd course and maintenance ECT Over 1 yr
Over 10 mo
(continued on foilowing page)
Movement Disorders, Vol. 6 , N o . 4 , 1991
R . FABER AND M . R . TRIMBLE
296
TABLE l-(Continued) Study Roth et al. (28) (1 988) Douyon et al. (29) (1989)
No. of patients 1
Patient history 62 yr old
I
Psychiatric morbidity
ECT parameters
Response duration
Results on PD
Manid and TD, both improved Depression
10 unilateral
Marked improvement
NS
7 bilateral
Rating scales used. 6 of 7 improved markedly in motor function
NS
No morbidity
NS
Excellent improvement in 5 of 5 with prominent rigidity and bradykinesia, no change in 3 of 3 with mainly Iremor, maximal response after 2-3 ECT courses Included in Balldin et al. (31) (1981) N o significant change, rating scale used
2-3 mo
Detailed ratings used, 5 marked improvement, 2 slight improvement, 2 no change Transient improvement
4 4 1 wk
No change with sham, 9 of 11 improved with real ECT
2-6 wk
Parkinsonism without psychiatric comorbidity Fromm (2) (1959)
Pre-r-dopa, PD of 5-20 yr’s duration
Balldin et al. (30) ( 1980) Ward et al. (32) (1980)
“On-off,” 2-7 yr
Bilateral
Average age 57, “on-off’ over 1 yr PD for 6-20 yr, “on-off’ for 2-7 yr
No morbidity
6 bilateral
No morbidity
3-8 bilateral
Berger and de Sot0 (34) ( 1990) Controlled studies
71 yr old
History of depresbion, mild dementia
6 unilateral
Anderson et al. (33) (1987)
Average age 70, 15 yr PD, “on-off’ 5 k 2 yr, on L-dopa
No morbidity
6 patients
Balldin et al. (31) (1981)
initially received sham ECT, then switched 4 to bilateral and 2 to unilateral; 5 received 5 6 bilateral initially
NS, not specified; TD, tardive dyskinesia.
peared” after three ECT treatments. Unfortunately, the authors did not indicate the duration of improvement or type of ECT. Yudofsky (18) described “marked improvement” in walking speed, postural stability, rigidity, selfcare, and manual dexterity as determined by rating scale assessment after 10 ECT treatments for delusional depression in a 66-year-old man. The patient experienced a sustained complete recovery from psychiatric symptomatology but his parkinsonian symptoms restarted in 3 days and in 1 week had returned to their pre-ECT level. Levy et al. (19) described a 76-year-old man with depression and PD who after 10 ECT treatments had substantially improved gait, speed, balance, and rigidity, which were maintained at 6-month follow-up observation. Holcomb et al. (20) administered 14 bilateral ECT treatments to a 72-year-old woman with delusional depression, PD, and coexisting tardive dyskinesia (TD). Marked improvements in depression and par-
Movement Disorders, Vol. 6 , No. 4, 1991
kinsonian symptoms were documented using rating scales, while the dyskinesias markedly worsened. Following the recurrence of PD and depression within 1 week, a second course of ECT again resolved these symptoms, which continued in remission with the administration of monthly maintenance ECT. Young et al. (21) described marked improvements in parkinsonian symptoms that persisted for over 1 year in a 73-year-old woman given seven unilateral ECT treatments for depression. This improvement was particularly notable since the depressive symptomatology went unchanged. The patient also evidenced moderately severe dementia, which remained unchanged over the period of study. Raskin (22) reported marked improvement in depression and complete resolution of idiopathic parkinsonism in a single patient that were both sustained by monthly maintenance ECT. Patient characteristics and ECT parameters were not specified.
ECT IN PARKINSON’S DISEASE Baruch et al. (23) described six patients with both depression and PD treated with ECT seven to 15 times. All had a good antidepressant response, while four of the six had notable improvement in their parkinsonism. Incredibly, at follow-up observation of 3-8 years, none of these four showed signs of PD or needed antiparkinsonian treatment. Jaeckle and Dilsaver (24) described a 59-year-old woman with a bipolar disorder who exhibited classic and severe symptoms of PD during several discrete depressive episodes. A course of nine bilateral ECT treatments brought about a remission of her psychotic depression and markedly improved her parkinsonian symptoms. Burke et al. (25) described treating three patients with coexisting PD and depression with ECT. All had remission from their depressive symptoms. One patient’s parkinsonism was much improved, another had marked improvement but the return of symptoms after 12 days, while the third patient’s parkinsonism remained unchanged. Atre-Vaidya and Jampala (26) described marked improvement of parkinsonism in a 72-year-old woman lasting over 10 months following 12 bilateral ECT treatments used to resolve a manic episode. Hurwitz et al. (27) successfully treated psychotic symptoms secondary to bromocriptine and L-dopa therapy with ECT in two PD patients. Rating scales revealed moderate improvement following ECT, which allowed the reinstitution of optimal doses of the medications. Roth et al. (28) described a 62-year-old man with coexistent mania, idiopathic parkinsonism, and TD. After a course of 10 right unilateral ECT treatments, his manic symptoms and TD remained unchanged, but all of his parkinsonian symptoms markedly improved. Douyon et al. (29) found ECT to improve depression and all aspects of PD in six of seven patients treated with an average of seven bilateral ECT treatments. Standardized rating instruments noted significant improvement in motor function after two ECT treatments. Final average ratings of impairment were 51% lower at the completion of ECT. Also of interest was the finding of a dissociation of antidepressant and antiparkinsonian effects in two of the patients. PARKINSON’S DISEASE WITHOUT PSYCHIATRIC COMORBIDITY Fromm’s report (2) on eight PD patients without psychiatric comorbidity noted that five of five patients with prominent rigidity and bradykinesia ob-
297
tained “noticeable remissions” (lasting 2-3 months) after two or three ECT treatments. Several bedridden patients became able to care for themselves and perform household duties for the first time in years. None of three patients with predominant tremor symptoms, including the only postencephalitic patient, responded substantially. Balldin et al. (30) reported the results of ECT given to five PD patients with prominent “on-off’ periods and without psychiatric comorbidity . These same five patients were included in a longer report on a total of nine PD patients with “on-off ’ symptoms and no significant psychiatric comorbidity , though a few patients were mildly depressed (31). Patients were given three to eight bilateral ECT treatments. Five of the nine showed marked improvement that lasted from 4-41 weeks. Their “off’ time decreased from 54 to 5% after ECT, with four of these five having no “off’ time after ECT. Two other patients had moderate improvement, with “off’ time decreasing from 52 to 26%, but their improvement was never marked and only lasted for 2 weeks. Finally, another two patients evidenced no improvement at all. Following the Balldin et al. (30) initial report, Ward et al. (32) reported on their experience in a similar patient population. They could detect no significant changes using rating scales in five PD patients without psychiatric comorbidity , each given six bilateral ECT treatments. They commented that these results ran counter to what had been their clinical experience. As an addendum, they described their results in a 57-year-old woman with PD and psychotic depression, both groups of symptoms improving significantly with three courses of ECT but eventually returning to former levels in spite of twice-weekly maintenance ECT. In 1987, Anderson et al. (33) did the first and only double-blind controlled study of ECT in PD. Again they observed patients with significant “off’ time and without psychiatric comorbidity or dementia. Six randomly assigned patients received five to six sham ECT treatments, identical to active treatment except that electric current was not given. Another five patients received five to six real bilateral ECT treatments. Striking differences were found in the percentage of “on” time, as the sham group remained unchanged but the active ECT group more than doubled its “on” time from 32 to 71%. Following their sham treatments, these six patients received real ECT, four patients bilaterally and two unilaterally. Their percentage of “on” time in-
Movement Disorders, Vol. 6, N o . #, 1991
R . FABER AND M . R . TRIMBLE
298
creased from 32 to 44%. Considering the effects of ECT on all 11 patients, two had marked improvement, seven had moderate improvement, and two did not have improvement. Of note was the short duration of improvement in light of the group’s prior report, ranging from only 2 to 6 weeks with a mean of just under 3 weeks in the nine responders. Berger and de Soto (34) described a 71-year-old man with severe PD and no evident psychopathologic condition who, during a course of six unilateral ECT treatments for his PD, had transient improvement after each treatment that quickly returned to baseline levels. DRUG-INDUCED PARKINSONISM In parallel with ECT improving idiopathic PD symptoms are reports of ECT ameliorating parkinsonism induced by neuroleptic drugs. Anath et al. (35) describe a 25-year-old schizophrenic man with catatonic symptoms refractory to fluphenazine, 6& 80 mglday. In the face of severe rigidity, tremor, and bradykinesia, a course of bilateral ECT was given, with marked improvement in both parkinsonism and psychopathology even as the fluphenazine was continued. Small et al. (36) found that patients treated with thiothixene plus ECT had fewer extrapyramidal symptoms (EPSS) than patients treated with thiothixene alone. Gangadhar et al. (37) assessed the effects of ECT on neuroleptic-induced parkinsonism in 17 nondepressed first-admission psychotic patients. Using the Simpson and Angus EPS rating scale, patients receiving over 500 chlorpromazine milligram equivalents and five ECT treatments obtained an average score of 1.0, which was significantly less than an average score of 5.5 from a well-matched control group of 18 patients who received equivalent medication without ECT for a similar duration. Goswani et al. (38) found that ECT significantly reduced the severity of neuroleptic-induced parkinsonism in nine schizophrenic patients observed in an A-B-A design: neuroleptics-neuroleptics plus nine bilateral ECT treatments for 3 weeksneuroleptics alone for 2 weeks. Parkinsonism scores declined steeply and significantly following the introduction of ECT, then increased gradually after completion of ECT. OTHER MOVEMENT DISORDERS Tardive Dyskinesia A number of case reports have described the effects of ECT on TD, with rather mixed results (39).
Movement Disorders, Vol. 6 , No. 4,1991
Asnis and Leopold (40) reported no effect from ECT on TD. They treated four women, each with TD and psychiatric decompensation. Blinded movement ratings of videotapes revealed no change in three patients and possible worsening in a fourth whose markedly fluctuating baseline ratings made conclusions tenuous. Price and Levin (41), however, reported nearly complete remission of TD in a 49-year-old woman given a course of seven ECT treatments, and Rosenbaum et al. (42) described a 74-year-old woman with recurrent agitated, depressive episodes who experienced a marked improvement of severe TD after a course of eight ECT treatments. Chacko and Root (43) reported dramatic remissions of severe TD in two women aged 62 and 63 years. Marked improvements began after their third and fourth ECT treatments and were sustained for 1- and 2-year follow-up examinations. The 62-yearold patient had, in addition, severe neuroleptic drug-induced EPSS of resting tremor, cogwheel rigidity, and akathisia, which all cleared concurrently with TD symptoms. Gosek and Weller (44) also described dramatic improvement in TD present for 5 years in a 54-yearold woman, when she was treated with ECT for a depressive episode. This improvement was sustained at follow-up observation 14 months later. Malek-Ahmadi and Weddige (45) described a remarkable reduction in dyskinetic movement in a 65year-old woman given five bilateral ECT treatments for depression with psychotic features. Tardive dyskinesia had been present for 10 years before ECT, but at 2-month post-ECT follow-up observation, only minimal, infrequent buccolingual movements were present. Based on a community survey in Hungary, Gardos et al. (46) noted a very low prevalence of TD in outpatient schizophrenics there. They speculated that the preferred practice of using ECT in place of high-dosage neuroleptics may have a protective effect in the development of TD. However, in a survey of 682 mental hospital patients of whom 196 had buccal-lingual-masticatory (tardive) dyskinesias, Brandon et al. (47) found no association between ECT exposure or number and the occurrence of TD. Other authors have suggested that ECT may contribute to the development of or exacerbate TD. Uhrbrand and Faurbye (48) ascribed four cases of TD to the administration of ECT. These were drawn from 33 cases of TD in a total psychiatric
ECT IN PARKINSON’S DISEASE population of 500 women. The extent of ECT given to the entire study population was not described, basing the ECT-TD relationship solely on the appearance of TD after the administration of ECT. Holcomb et al. (20), in their case report of a 72year-old man with a delusional depression, described marked worsening of TD while depressive and PD symptoms greatly improved with a course of ECT. Flaherty et al. (49) described three cases of reversible buccolingual dyskinesia emerging during the course of ECT without concurrent or recent neuroleptic drug administration. The dyskinesia lasted in each respective case for 3 months, 2 weeks, and 4 weeks. In their case report of coexisting mania, PD, and TD, Roth et al. (28) found ECT to alleviate PD and manic symptoms, with choreoathetoid limb movements resolving while severe orofacial and lingual dyskinesias appeared. Fahn et al. (50) described ECT relieving severe, intractable tardive akathisia and TD in three patients. These mixed reports of ECT sometimes ameliorating and sometimes worsening TD would suggest heterogeneity in the underlying biochemical pathophysiology of TD. Other Conditions We could find only two case reports of tardive dystonia treated with ECT. Kwentus et al. (51) described a 52-year-old woman with extensive prior neuroleptic exposure who exhibited sustained opisthotonic trunk extension with retrocollis and sustained extension movement of the arms. The patient received a course of nine nondominant, unilateral ECT treatments for catatonia associated with depression. Along with completely relieving all depressive symptoms, the dystonias abated except for some hyperextension of the wrists. Adityanjee et al. (52) described a 30-year-old man with a history of schizophrenia treated with antipsychotic drugs since age 17. He began a course of ECT after a I-month history of severe anterocollis. Auditory hallucinations disappeared after four treatments while the tardive dystonia began to improve after six ECT treatments. After 11 treatments, the dystonia was remarkably improved. At 2-month followup observation, there was a moderate recrudescence of the dystonia. In a mental hospital survey, Friedman et al. (53) suggested that ECT may be a risk factor for the emergence of tardive dystonia, as two of the five patients they identified as having tardive dystonia
299
were previously treated with ECT. They do not, however, report the percentage of patients without tardive dystonia (n = 326) who had received ECT. They present no statistical basis for their conclusion. Araneta et al. (54) described a case of Gilles de la Tourette’s syndrome in a man with symptom onset at age 35. After neuroleptics no longer provided relief for severe symptomatology, a course of ECT was administered, to no avail. In a report on the use of ECT in one child and three adolescents, Guttmacher and Cretella (55) described a 15-year-old boy with Gilles de la Tourette’s syndrome and childhood-onset pervasive developmental disorder. Though a course of seven bilateral ECT treatments brought about a dramatic improvement in a concurrent mood disorder, this was not accompanied by any change in motor and speech functioning. Swerdlow et al. (56) described a 65-year-old man with a disabling tic and a major depressive episode. The patient’s motor and affective symptoms resolved after ECT, and he remained asymptomatic at 1-year follow-up observation. Transient bilateral upper limb asterixis lasting for 2 h was noted after two of 10 ECT treatments given to a 48-year-old woman treated for mania and later found to have primary hyperparathyroidism (57). MECHANISM OF ACTION A suggested mechanism for the efficacy of ECT in PD has been discussed by Fochtmann (58) with an emphasis on the effects of electroconvulsive shock (ECS) on animal dopamine systems. Nomikos et al. (50) found massive increases in interstitial striatal dopamine using dialysis probes in freely moving rats given ECS. Long-term (as opposed to short-term) ECS enhances a variety of dopaminemediated behaviors stimulated by apomorphine, amphetamine, or L-dopa plus tranylcypromine (6062). Costain et al. (63) found ECT in depressed patients to increase the growth hormone response to apomorphine. Though Chiodo and Antelman (64) found progressive dopamine autoreceptor subsensitivity independent of repeated treatment after ECS, the dopaminergic effects of ECS have been suggested to occur at least postsynaptically (65) or even further downstream of the receptor at its effector-coupled system (66). Recent work suggests prominent ECS effects on D, receptors (67). Sershen et al. (68) found ECS to significantly increase D, binding activity in control and MPTP-treated mice without affecting D, receptor activity. Sharp
Movement Disorders, Vol. 6, No. 4, 1991
300
R . FABER AND M . R . TRIMBLE
et al. (69) found ECS-enhanced behavior with the D, (SFK38393) and mixed (apomorphine) dopamine agonists but not with a specific D, agonist (RU24213). While Fochtmann et al. (70) found increased D, receptor binding in the substantia nigra of rats after long-term ECS, Martin et al. (71) found no such ECS effect and Klimek and Neilson (72) detected a decrease in D, binding sites in the nucleus accumbens. In addition to these findings regarding D, receptor binding, striatal binding of the D, receptor ligand, spiperone, is also affected by ECS (73-76). The physiological relationship of D, and D, receptors is such that D, receptor activation is required to obtain full expression of the D, receptor site, which has typically been associated with the clinical benefits of dopaminergic therapy in PD (77-80). An up-regulation of D, receptors is thus proposed as a mechanism for the antiparkinsonian effect of ECT. Nondopaminergic systems affected in PD may also be modified by ECT. In PD the ascending noradrenergic ceruleocortical system is reduced by about 50% (81) while, as an apparent compensation, cortical beta,-adrenergic receptors are increased (82). Repeated ECS down-regulates the cortical beta-adrenoreceptor number (83), a phenomenon it shares with all known effective antidepressant treatments but without known direct relevance on motor systems. Changes in brain gamma-aminobutyric acid (GABA) in PD are debated. While reductions in GABAergic systems have been reported, this may simply be secondary to loss of GABA-sensitive dopaminergic nigrostriatal neurones (81). Striatal GABA concentrations are increased by ECS (84) and GABA-B receptors have been reported to increase with repeated ECS (85). The findings that D, receptors are located presynaptically on striatal GABAergic neurons (86) could link both dopamine and GABA systems to the antiparkinsonian effect of ECT. Although serotoninergic systems are moderately reduced in PD, these changes are not believed to be related to parkinsonian symptoms (81). Electroconvulsive shock reduces serotonin- 1A presynaptic receptors and up-regulates serotonin-2 postsynaptic receptors (87); these changes are believed to be extremely relevant in mediating antidepressant effects (88,89). Although cholinergic systems are mainly intact in the basal ganglia in PD, cortical and hippocampal cholinergic systems are diminished to varying de-
Movement Disorders, Vol. 6,N o . 4, 1991
grees. This latter diminishment in cholinergic systems may contribute to the cognitive dysfunction that can be associated with PD. Dopamine and cholinergic links have historically been a major avenue for therapeutic interventions in PD. Electroconvulsive shock induces a small downregulation in cortical muscarinic cholinergic receptors (90). Various peptides are reduced in PD, but none of these deficiencies correlates with parkinsonian symptoms or response to treatment. Electroconvulsive shock can increase encephalin concentration, but no consistent peptide changes have been reported in this little-studied area (91). In discussing the role of glutamate in the basal ganglia, Suedfeld et al. (92) proposed that ECT benefits PD by decreasing glutamatergic function. Summarized in Table 2, various neurotransmitter systems are perturbated in PD, and repeated ECS/ ECT causes many neuroadaptive responses. It is ECT’s effect on increasing postsynaptic dopamine function that seems most relevant to its antiparkinsonian action. This effect would also explain the exacerbation of TD in some reports. The more consistent results of ECT on PD in comparison with the other movement disorders reviewed emphasize the differences in the underlying biochemistry of the various disorders. DISCUSSION This review of the literature suggests that ECT has antiparkinsonian effects, independent of any effects on mental state. The predictability, magniTABLE 2. Neurotransmitters in ECT and PD PD Dopamine
Decreased 80%
D1 D2
Norepinephrine GABA
Decreased but beta, receptors increased Decreased
Serotonin
Decreased
Acetylcholine
Minimal changes, decrease in cortical and hippocampal systems
ECT Increased receptor responsiveness Increased receptor activation Increased receptor binding, apomorphine-growth hormone enhancement, apomorphine-prolactin reduction Decreased beta, receptors Concentration increased, receptors increased S-HT,, presynaptic receptors decreased, 5-HT, postsynaptic receptors increased Minimal changes, slight downregulation of cortical mucarinic receptors
ECT, electroconvulsive therapy; PD, Parkinson’s disease.
ECT IN PARKINSON’S DISEASE tude, and duration of such effects, however, cannot be well specified. The reports have largely been poorly controlled, unblinded, with failure to attempt objective assessment of PD symptoms. Nonetheless, several studies are substantially better designed, including the Anderson et al. (33) double-blind sham-controlled study. It is on the basis of these data that we offer these conclusions. This review examines the results of 27 reports on 78 patients with idiopathic PD. We tabulate that 48 patients obtained definite, meaningful clinical benefit sustained for at least 2 weeks while 30 did not. While most of the reports we cite have been retrospective and undoubtedly the literature is biased by the underreporting of negative cases, three prospective studies (29,32,33) cumulatively found improvement in 15 of 23 patients. We speculate that approximately half of PD patients who receive ECT may be expected to benefit clinically. This is aside from the 80% response rate expected when treating depression or psychosis. Such responses are certainly worthy of further investigation. We counted four of eight unilaterally treated patients positively, in contrast to 44 of 70 patients with bilateral treatments. Given the notable difference in cognitive side effects between those electrode placements (92) and the problems of cognitive dysfunction in PD, further study of electrode position is warranted. The length of treatment and timing of ECTs requires exploration. The onset of antiparkinsonian ECT effects varies considerably from rather immediate to requiring a “full course” of between six and 10 treatments. While the distinction of improvement sustained for more than 2 weeks is more valid clinically at this point, transient improvement noted by Yudofsky (18) and Burke et al. (25) implies that neurochemical changes are induced that, if they could be harnessed and prolonged, would also be therapeutically meaningful. Several authors (20,22) have advocated maintenance ECT in PD, as is sometimes used in severe relapsing affective disorders. We would suggest that PD patients who have an unsatisfactory response to conventional treatments be considered for a course of up to eight bilateral ECT treatments given two to three times per week. The literature on unilateral ECT for PD is too scanty to recommend it at this time. If the transient confusion and amnesia from bilateral ECT become major problems, spacing the treatments further apart usually reduces such side effects to acceptable levels. If ECT brings about clinically
301
significant improvement that lasts at least 1 month, we would continue maintenance ECT at about monthly intervals. Our review also suggests a role for ECT in the management of drug-induced parkinsonism (93) and TD. The judicious combination of ECT with neuroleptics may cause fewer motor side effects than neuroleptics alone and for some patients may also be more efficacious (94). Other drug-induced movement disorders have not been studied sufficiently to warrant comment. In summary, though the literature we reviewed is more notable for its quantity than its quality, we conclude that approximately half of patients with severe PD might be expected to have a meaningful clinical response of sufficient duration to make ECT a worthwhile adjunctive consideration when current therapies are unsatisfactory, especially if maintenance ECT can be continued when warranted. Acknowledgment: We are grateful to Dr. Eileen Smith for reviewing and editing this manuscript and thank Ann Martin and Joanna McNamara for expert manuscript preparation.
REFERENCES 1. Gallinek A. Electric convulsive therapy in geriatrics. NY
State J Med 1947;47:1233-1241. 2. Fromm GH. Observations of the effect of electroshock treatment on patients with parkinsonism. Bull Tulane Univ Med Faculty 1959;18:71-73. 3. Kalinowsky LB. Die Electrokrampfbehandlungin ihrer Beziehung zur Neurologie. Monatsschr Psychiatr Neuroll949; 177:268-279. 4. Kaplan LA, Freund DJ. Electroshock therapy in patients with severe organic disease. I / / Med J 1949;95:96-101. 5. Savitsky N , Karliner W. Electroshock in the presence of organic disease of the central nervous system. J Hillside HOSP 1953;2:3-22. 6. Shapiro MF, Goldberg HH. Electroconvulsive therapy in patients with structural disease of the central nervous system. Am J Med Sci 1957;233:186-195. 7. Ehrenberg R, Gullingsrud MJO. Electroconvulsive therapy in elderly patients. Am J Psychiatry 1955;111:743-747. 8. Wolff GE. Electric shock treatment. Am J Psychiatry 1955; 1 1 1 :748-750. 9. Tucker WI, Fleming R, Raeder 0 . Electroconvulsive treatment in a general hospital. N Engl J Med 1955;253:451-454. 10. Lebensohn ZM, Jenkins RB. Improvement of parkinsonism in depressed patients treated with ECT. Am J Psychiatry 1975;132:283-285. 11. Lipper S, Bermanzohn PC. Electroconvulsive therapy in patients with parkinsonism. Am J Psychiatry 1975;132:457. 12. Brown GC. Parkinsonism, depression and ECT. Am J Psychiatry 1975;132:1084. 13. Lebensohn ZM. Parkinsonism, depression and ECT. Am J Psychiatry 1975;132:1084. 14. Rainey JM, Faust M. Parkinsonism masked by ECT and psychotropic medication. Am J Psychiafry 1975;132:10841085.
Movement Disorders, Vol. 6 , No. 4, 1991
302
R . FABER AND M . R . TRIMBLE
15. Dysken M, Evans HM, Chan CH, et al. Improvements of depression and parkinsonism during ECT. Neuropsychobiology 1976;2:81-86. 16. Asnis G. Parkinson’s disease, depression, and ECT: a review and case study. A m J Psychiatry 1977;134:191-195. 17. Barcia D, Martinez PF. Cuadros depresivos en enfermedad de Parkinson tratados con electroshock. Arch Neurobiol 1978;41:393-398. 18. Yudofsky SC. Parkinson’s disease, depression, and electroconvulsive therapy: a clinical and neurological synthesis. Compr Psychiatry 1979;20:579-581. 19. Levy LA, Savit JM, Hodes M. Parkinsonism: improvement by electroconvulsive therapy. Arch Phys Med Rehabil 1983; 64:432433. 20. Holcomb HH, Sternberg DE, Heninger GR. Effects of electroconvulsive therapy on mood, parkinsonism, and tardive dyskinesia in a depressed patient: ECT and dopamine systems. Biol Psychiatry 1983;18:865-873. 21. Young RC, Alexopoulos GS, Shamoian CA. Dissociation of motor response from mood and cognition in a parkinsonian patient treated with ECT. Biol Psychiatry 1985;20:566-569. 22. Raskin D. Can ECT cure Parkinson’s disease? 138th Annual Meeting of the American Psychiatric Association. Abstracts of the New Research Program. Dallas: TX, 1985. 23. Baruch P, Jouvent R, Vindreau C, Drouillon C, Widlocher D, Agid Y . Improvements of parkinsonism in ECT-treated depressed patients: Parkinson’s disease and depressionrelated extra-pyramidal disorder? In: Abstracts of the IVth World Congress of Biological Psychology. Philadelphia: PA, 1985. 24. Jaeckle RS, Dilsaver SC. Covariation of depressive symptoms, parkinsonism, and post-dexamethasone plasma cortical levels in bipolar patients: simultaneous response to ECT and lithium carbonate. Acta Psychiatr Scand 1986;74:68-72. 25. Burke WJ, Peterson J, Rubin EH. Electroconvulsive therapy in the treatment of combined depression and Parkinson’s disease. Psychosomatics 1988;29:341-346. 26. Atre-Vaidya N, Jampala VC. Electroconvulsive therapy in parkinsonism with affective disorder. Br J Psychiatry 1988; 152:55-58. 27. Hunvitz TA, Calne DB, Waterman K. Treatment of dopaminomimetic psychosis in Parkinson’s disease with electroconvulsive therapy. Can J Neurol Sci 1988;15:32-34. 28. Roth SD, Mukherjee S, Sacheim HA. Electroconvulsive therapy in a patient with mania, parkinsonism, and tardive dyskinesia. Convulsive Ther 1988;4:92-97. 29. Douyon R, Serby M, Klutchko B, Rotrosen J. ECT and Parkinson’s disease revisited: a “naturalistic” study. Am J Psychiatry 1989;146:1451-1 455. 30. Balldin J, Eden S, Granerus AK, et al. Electroconvulsive therapy in Parkinson’s syndrome with “on-off’ phenomenon. J Neural Transm 1980;47:11-21. 31. Balldin J, Granerus AK, Lindstedt G, Modigh K, Wallinder J. Predictors for improvement after electroconvulsive therapy in a parkinsonian patient with “on-off’ symptoms. J Neural Transm 1981;52:199-21 1. 32. Ward C, Stem GM, Pratt RTC, McKenna P. Electroconvulsive therapy in parkinsonian patients with the “on-off” syndrome. J Neural Transm 1980;49:133-135. 33. Anderson K, Balldin J, Gottpries CG, et al. A double-blind evaluation of electroconvulsive therapy in Parkinson’s disease with “on-off’ phenomena. Acta Neurol Scand 1987; 76:191-199. 34. Berger M, de Soto DA. The use of ECT for parkinson symptoms in a nondepressed patient. Psychosomatics 1990;31: 465466.
Movement Disorders. Vol. 6, N o . 4, 1991
35. Anath J, Samra D, Kolivakis T. Amelioration of druginduced parkinsonism by ECT. A m J Psychiatry 1979;136: 1094. 36. Small JG, Milstein V, Klapper M, Kellams JJ, Small IF. ECT combined with neuroleptics in the treatment of schizophrenia. Psychopharmacol Bull 1982;18:34-35. 37. Gangadhar BN, Roychowdhury J, Channabasavanna SM. ECT and drug-induced parkinsonism. Indian J Psychiatry 1983;25:212-2 13. 38. Goswani U, Duttaq S, Kuruvilla K, Papp E, Perengi A. Electronconvulsive therapy in neuropeptic-induced parkinsonism. Biol Psychiatry 1989;26:234-238. 39. Hay DP, Hay L, Blackwell B, Spiro HR. ECT and tardive dyskinesia. J Geriatr Psychiatry Neurol 1990;3:106-109. 40. Asnis GM, Leopold MA. A single-blind study of ECT in patients with tardive dyskinesia. Am J Psychiatry 1978;135: 1235-1238. 41. Price TRP, Levin R. The effects of electroconvulsive therapy on tardive dyskinesia. Am J Psychiatry 1978;135:991993. 42. Rosenbaum AH, O’Connor MK, Duane DD, Auger RG. Treatment of tardive dyskinesia in an agitated, depressed patient. Psychosomatics 1980;21:765-766. 43. Chacko RC, Root L. ECT and tardive dyskinesia: two cases and a review. J Clin Psychiatry 1983;44:265-266. 44. Gosek E, Weller RA. Improvement of tardive dyskinesia associated with electroconvulsive therapy. J Nerv Men1 Dis 1988;176:120-122. 45. Malek-Ahmadi P, Weddige RL. Tardive dyskinesia and electroconvulsive therapy. Convulsive Ther 1988;4:328-331. 46. Gardos G, Samu I, Kallos M, Cole JO. Absence of severe tardive dyskinesia in Hungarian schizophrenic outpatients. Psychopharmacology 1980;71:29-34. 47. Brandon S, McClelland HA, Protheroe C. A study of facial dyskinesia in a mental hospital population. Br J Psychiatry 1971;118:171-184. 48. Uhrbrand L, Faurbye A. Reversible and irreversible dyskinesia after treatment with perphenazine, chloropromazine, reserpine, and electroconvulsive therapy. Psychopharmacologin 1960;1 :40W18. 49. Flaherty JA, Naidu J, Dysken M. ECT, emergent dyskinesia, and depression. Am J Psychiatry 1984;141:808-809. 50. Fahn S, Brin M, Bressman S. Relief of intractable, disabling tardive akathisia and tardive dyskinesiddystonia with electroconvulsive therapy (ECT) [Abstract]. American Neurological Association Meeting, September 1989. New Orleans: LA, 1989. 51. Kwentus JA, Schulz SC, Hart RP. Tardive dystonia, catatonia, and electroconvulsive therapy. J Nerv Ment Dis 1984; 172: 171-173. 52. Adityanjee, Jayaswal SK, Chan TM, Subramaniam M. Temporary remission of tardive dystonia following electroconvulsive therapy. Br J Psychiatry 1990;156:433435. 53. Friedman JH, Kucharski LT, Wagner RL. Tardive dystonia in a psychiatric hospital. J Neurol Neurosurg Psychiatry 1987;50:801-803. 54. Araneta E, Magen J, Musci MN, Singer P, Vann CR. Gilles de la Tourette’s syndrome-symptom onset at age thirtyfive. Child Psychiatry Hum Dev 1975;5:224230. 5 5 . Guttmacher LB, Cretella H. Electroconvulsive therapy in one child and three adolescents. J Clin Psychiatry 1988;49: 20-23. 56. Swerdlow NR, Gierz M, Berkowitz A, Nemiroff R, Lohr J. Electroconvulsive therapy in a patient with severe tic and major depressive episode. J Clin Psychiatry 1990;51:3435. 57. Dysken MW, Halaris AE. Post-ECT asterixis associated
ECT IN PARKINSON'S DISEASE with primary hyperparathyroidism. Am J Psychiatry 1978; 135:1237-1238. 58. Fochtmann L. A mechanism for the efficiency of ECT in Parkinson's disease. Convulsive Ther 1988;4:321-327. 59. Nomikos GG, Zis AP, Damsma G, Fibiger HC. Electroconvulsive shock produces large increases in interstitial concentrations of dopamine in the rat straitum: an in vivo microdialysis study. Neuropsychopharmacology 1991;4:65-69. 60. Modigh K, Balldin J, Eriksson E, Granerus AK, Walinder J. Increased responsiveness of dopamine receptors after ECT: a review of experimental and clinical evidence. In: Lerer B, Weiner RD, Belmaker RH, eds. ECT: basic mechanisms. London: John Libby, 1984:18-27. 61. Green AR, Nutt DJ. Psychopharmacology of repeated seizures: possible relevance to the mechanism of action of electroconvulsive therapy. In: lverson LL, Iverson SD, Snyder SH, eds. Handbook of psychopharmacology. Vol. 19. New York: Plenum Press, 1987:375419. 62. Lerer B. Neurochemical and other consequences of ECT. Implications for the pathogenesis and treatment of affective disorders. In: Meltzer HL, ed. Psychopharmacology: the third generation of progress. New York: Raven Press, 1987:577-588. 63. Costain DW, Cowen PJ, Gelder MG, Grahame-Smith DG. Electroconvulsive therapy and the brain: evidence for increased dopamine-mediated responses. Lancet 1982;2:400404. 64. Chiodo LA, Antelman SM. Electroconvulsive shock: progressive dopamine autoreceptor subsensitivity independent of repeated treatment. Science 1980;210:799-801. 65. Green AR, Heal DJ, Grahame-Smith DG. Further observations on the effect of repeated electroconvulsive shock on the behavioural responses of rats produced by increases in the functional ability of brain 5-hydroxytryptamine and dopamine. Psychopharmacology 1977$2: 195-200. 66. Heal DJ, Green AR. Repeated electroconvulsive shock increases the behavioral responses of rats to injection of both dopamine and dibutyryl cyclic AMP into the nucleus accumbens. Neuropharmacology 1978;17:1085-1087. 67. Nowak G, Zak J. Repeated electroconvulsive shock (ECS) enhances striated D-1 dopamine receptor turnover in rats. Eur J Pharmacol 1989;167:307-308. 68. Sershen H, Wolinsky T, Douyon R, et al. The effects of electroconvulsive shock on dopamine-1 and dopamine-2 receptor ligand binding activity in MPTP-treated mice. J Neuropsychiatry Clin Neurosci 1991;3:58-63. 69. Sharp T, Kingston J, Grahame-Smith DG. Repeated ECS enhances dopamine D-1 but not D-1 agonist-induced behavioral responses in rats. Psychopharmacology 1990;lOO: 110-1 14. 70. Fochtmann LJ, Cruciani R, Aiso M, Potter WZ. Chronic electroconvulsive shock increases D-1 receptor binding in rat substrantia nigra. Eur J Pharmacol 1989;167:305-306. 71. Martin WR, Sloessl AJ, Palmer M, et al. Pet scanning in dystonia. Adv Neurol 1988;50:223-229. 72. Klimek V, Neilson M. Chronic treatment with antidepressants decreases the number of 3H-SCH23390 binding sites in the rat striatum and limbic system. Eur J Pharmacol 1987; 139: 163-169. 73. Bergstrom DA, Kellar KJ. Effect of electroconvulsive shock on monoaminergic receptor binding sites in rat brain. Nature 1979;278:464-466. 74. Deakin JF, Owen F , Cross AJ, Dashwood MJ. Studies on possible mechanisms of action of electroconvulsive therapy; effects of repeated electrically induced seizures on rat brain receptors for monoamines and other neurotransmitters. Psychopharrnacology 1981;73:345-349. 75. Lerer B, Belmaker RH. Receptors and mechanism of action
303
of electroconvulsive therapy. Biol Psychiatry 1982;17:497511. 76. Gulati A, Srimai RC, Dhawan KN, Dhawan BN. On the mechanism of potentiation of apomorphine-induced stereotypy due to electroconvulsive shock. Neuropharmacology 1987;26:1733-1737. 77. Beaulieu M. Clinical importance of D-1 and D-2 receptors. Can J Neurol Sci 1987;14:402406. 78. Clark D, White FJ. Review: DI dopamine receptor-the search for a function: a critical evaluation of the DUD2 dopamine receptor classification and its functional implications. Synapse 1987;1:347-388. 79. Creese I. Biochemical properties of CNS dopamine receptors. In: Meltzer HL, ed. Psychopharmcology: the third generation of progress. New York: Raven Press, 1987:257264. 80. Nomikos GG, Zis AP, Damsma G, Fibiger HC. Electroconvulsive shock and dopamine neurotransmission [Abstract]. Biol Psychiatry 1990;27:143A. 81. Agid Y , Javoy-Agid F, Ruberg M. Biochemistry of neurotransmitters in Parkinson's disease. In: Marsden CD, Fahn S, eds. Movement disorders 2. London: Butterworths, 1987: 166-230. 82. Cash R, Ruberg M, Raisman R, Agid Y . Adrenergic receptors in Parkinson's disease. Brain Res 1984;322:269-275. 83. Belmaker RH, Lerer B, Bannet J, Birmaker B. The effect of electroconvulsive shock at a clinically equivalent schedule on rat cortical beta-adrenoreceptors. J Clin Pharmacol 1982;34:275. 84. Green AR, Sant K, Bowdler JM, Cowen PJ. Further evidence for a relationship between changes in GABA concentration in rat brain and enhanced monoamine activated behaviours following repeated electroconvulsive shock. Neuropharmacology 1982;21:981-984. 85. Lloyd KG, Perrault G, Zivkovic B. Implications of GABAergic synapses in neuropsychiatry. J Pharmacol 1985; 16(suppl 2):5-27. 86. Porceddu ML, Giogi 0, Ongini E, Mele S , Biggio G. 3H SCH23390 binding sites in the rat substantia nigra: evidence for a presynaptic localization and innervation by dopamine. Life Sci 1986;39:321-328. 87. Green AR, Johnson P, Nemgaunkar VL. Increased 5-HT receptor number in the brain as a probable explanation for behaviour folthe enhanced 5-hydroxytryptamine-mediated lowing repeated electroconvulsive shock administration to rats. Br J Pharmacol 1983;80: 173-177. 88. Grahame-Smith DG, Green AR, Costain DW. Mechanism of the antidepressant action of electroconvulsive therapy. Lancet 1978;1:25&257. 89. Lerer B, Shapira B. Neurochemical mechanisms of mood stabilization: focus on electroconvulsive therapy. Ann N Y Acad Sci 1985;462:366-375. 90. Lerer B, Sitaram N. Clinical strategies for evaluating electroconvulsive therapy mechanisms-pharmacological, biochemical and psychophysiological approaches. Prog Neuropsychopharmacol Biol Psychiatry 1983;7:309-333. 91. Holaday JW, Belenky GL. Opiate-like effects of electroconvulsive shock in rats: a differential effect on nociceptive measures. Life Sci 1980;27:1929-1938. 92. Suedfeld P, Ramirez CE, Remick RA, Fleming JA. Reduction of post-ECT memory complaints through brief, partial restricted environmental stimulation. Prog Neuropsychopharmacol Biol Psychiatry 1989;13:693-700. 93. Fink M. ECT for Parkinson's disease? Convulsive Ther 1988;4: 189-19 1. 94. Greenberg LB, Mofson K, Fink M. Prospective electroconvulsive therapy in a delusional depressed patient with a frontal meningioma. Br J Psychiatry 1988;153:105-107.
Movement Disorders, Vol. 6,No. 4, 1991
Review
Electroconvulsive Therapy in Parkinson’s Disease and Other Movement Disorders *Raymond Faber and ?Michael R. Trimble *Department of Psychiatry, University of Texas Health Science Center at San Antonio and Audie L . Murphy Memorial Veterans Hospital, San Antonio, Texas, U . S . A . ,and ?National Hospitals and Institute of Neurology, Queen Square, London, England
Summary: Early case reports note marked improvements in the signs of Parkinson’s disease (PD) in several patients with coexisting psychiatric disorders after treatment with electroconvulsive therapy (ECT). Studies since 1959 reveal improvement of parkinsonism in over half of PD patients receiving ECT, regardless of the presence or absence of psychiatric comorbidity. Druginduced parkinsonism, tardive dystonia, and tardive dyskinesia have also been shown to improve with ECT administration; tic syndromes have achieved mixed results. In animals, ECT enhances dopamine-mediated effects and increases GABA concentrations in the CNS. Optimal parameters relevant to the antiparkinsonism effects of ECT require further study. Key Words: Electroconvulsive therapy-Movement disorders-Parkinson’s disease.
that the case descriptions were submitted for publication. There have been six reports on the result of ECT on PD without psychiatric comorbidity. One of these was a single case report; four were open studies of consecutive PD patients given ECT for severe, usually “on-off,” symptomatology , and one recent study used a double-blind methodology with sham ECT as a control. We have divided the literature into case reports and continuous series with psychiatric comorbidity, and continuous series and studies without psychiatric comorbidity. The less extensive and more ambiguous literature on ECT in some other movement disorders is also summarized.
i n this review, the literature on the effects of electroconvulsive therapy (ECT) on the motor disabilities of Parkinson’s disease (PD) and other movement disorders is examined. The available data are not widely appreciated but do lead to the conclusion that there is a role for ECT in the management of some cases of PD. Beginning with the observations of Gallinek in 1947 (I), there have been 35 reports on PD and ECT. Modern studies beginning with Fromm in 1959 (2) include 14 single case reports, while another seven have been case reports on from two to seven patients. These account for 33 separate patients, all of whom had a coexisting psychiatric condition that was the indication for the administration of ECT. It is notable that in these instances, the results of ECT on PD signs were often so marked
PD WITH PSYCHIATRIC COMORBIDITY Early History
Address correspondence and reprint requests to Dr. R. Faber, Department of Psychiatry, Audie L. Murphy Memorial Veterans Hospital, 7400 Merton Minter Drive, San Antonio, TX 78284, U.S.A.
Eight reports from the 1940s and 1950s, which mainly pertained to the safe administration of ECT
293
294
R . FABER AND M . R. TRIMBLE
to geriatric and medically ill patients, include mention of over 20 parkinsonian patients, some of whom had significant improvements in their motor disabilities. Kalinowsky (3) described improvement in both parkinsonian symptoms of 7 years’ duration and depression in a 68-year-old woman given six ECT treatments. Since this case was prototypical, we will translate and quote it in some detail. Twelve years ago, Y, a 68-year-old woman, had a psychotic episode with delusions of persecution which lasted for several months. Seven years ago she began showing symptoms of Parkinson’s disease. Her face became expressionless and her movements became slowed. A few weeks prior to her first hospitalization in the Neurological Institute in July 1945, she showed psychological changes and at the same time became totally immobile. At admission she presented the typical picture of severe parkinsonism. Psychiatrically hallucinations and delusions predominated; she believed herself to be in prison, heard the voices of police officers and was in a state of constant fear and agitation. She received 6 electroshock treatments during which the psychotic picture abated completely. Simultaneously with the psychiatric improvement, the stiffness of the various muscle groups receded to such an extent that the patient could not only walk at discharge, but was capable of total self care, although she retained symptoms of parkinsonism such as mask facies, lack of associated movements and moderate rigidity. One year later, in August 1946, she again suffered a depression with delusions. Again she became totally immobile during that episode. The psychosis resolved after 5 ECTs and her ability to walk returned after 3 treatments.
Negative findings were also reported, however, by Kaplan and Freund (4), who treated four patients with parkinsonism and mental changes and noted no effects on any parkinsonian symptoms. Savitsky and Karliner (5) described the effects of ECT on seven patients with PD and depression. In four of these seven parkinsonism was unchanged, two patients had remission of tremor though rigidity persisted, while another patient had improvement of both tremor and rigidity. Shapiro and Goldberg (6) treated three patients with depression and PD with ECT and described improvement of parkinsonian signs in one. Between 1947-55 there were four publications concerning the safe administration of ECT to geriatric and medically ill patients with coexisting psychiatric disorders. Gallinek (1) described a 64-yearold woman with a 3-year history of PD. Eight ECT
Movement Disorders, Vul. 6, No. 4, 1991
treatments induced a remission of her depression while her parkinsonism was unchanged. In three separate series, each including over 100 participants (7-9), several patients with PD safely received ECT with no mention made of any change in neurologic status. Modern Reports We have listed all 27 modern reports on PD and ECT in Table 1 . Lebensohn and Jenkins (10) described “marked improvement” in each of two patients after four sessions of ECT. One patient had mainly rigidity; the other had prominent rigidity and tremor. In both, the improvement lasted for “many months.” Lipper and Bermanzohn (1 1) described a 54-yearold man with PD who, after seven ECT sessions for psychotic depression, regained “good control” with the reinstitution of his prior L-dopa dose. No unique benefits were ascribed to his ECT. In a letter, Brown (12) reported a “poorer than usual” antidepressant effect in seven PD patients, each given one to four courses of eight ECT treatments per course. He makes no mention of any improvement in PD symptoms. Of note, however, was the fact that all seven of his patients showed moderate to severe dementia before ECT was given. In three patients described by Lebensohn (13), one evidenced “striking improvement,” one “moderate improvement,” and the other little improvement in parkinsonian symptoms while being treated for depression. Rainey and Faust (14) claimed that three ECT courses over 3 years reduced and temporarily relieved signs of parkinsonism in a delusionally depressed man who had also intermittently received neuroleptic medication but whose diagnosis by a neurologist was primary parkinsonism. Dysken et al. (15) described in great detail a 69year-old man with PD who received 12 bilateral ECT treatments for depression. A partially blinded rater used a formal rating scale to document substantial improvement in rigidity and bradykinesia with no alteration in tremor. Asnis (16) treated a 61-year-old man with depression and PD with six bilateral ECT treatments, obtaining an excellent antidepressant response and marked overall improvement in PD symptoms evaluated by rating scales. However, when the patient was observed 7 weeks after treatment, both depressive and parkinsonian symptoms had returned to pre-ECT baseline levels. Barcia and Martinez (17) described a 70-year-old man with both depression and PD that “disap-
ECT IN PARKINSON’S DISEASE
295
TABLE 1. Electroconvulsive therapy (ECT) effects on Parkinson’s diseuse (CPD) ~~
No. of Study
Patient history
patients
Psychiatric morbidity
ECT parameters
~
Response duration
Results on PD
Parkinsonism with psychiatric comorbidity Lebensohn and Jenkins (10) (1975)
2
Lipper and Bermanzohn (1 I ) (1975)
I
Brown (12) (1975)
7
Lebensohn (13) (1975)
3
Rainey and Faust (14) (1975)
1
Dysken et al. (IS) (1976)
1
Asnis (16) (1977)
4 treatments
PD 7 yr
Psychotic depression and bipolar depression, respectivefy Psychotic depression
Average age 67, all moderately to severelv demented NS
Depression, obtained “poorer than usual” ECT antidepressant response Depression
1-4 courses, 8 sessions per course
65 yr old, no L-dopa, prior neuroleptic exposure 69 yr old. prior treatment with thioridazine
Depression
3 courses over 3 yr
Depression
12 bilateral
1
61 yr old, 4 yr PD,
Depression
6 bilateral
Barcia and Martinez (17) ( I 978) Yudofsky (18) (1979)
1
prior L-dopa 70 yr old
Depression
3 ECT
1
66 yr old, 2 yr PD, prior r-dopa
Delusional depression
10 ECT
Ward et al. (32) (1980)
1
57 yr old, 10 yr PD, on r-dopa
Psychotic depression
3 courses of
Levy et al. (19) (1983)
1
76 yr old, PD 18 yr, on L-dopa
Depression
10 ECT
Holcomb et al. (20) (1983)
1
72 yr old, concurrent TD
Delusional depression
14 bilateral
Young et al. (21) (1985)
1
Marked improvement
1
Depression unrelieved by ECT, dementia also present Depression
7 unilateral
Raskin (22) ( 1985)
73 yr old, “on-off ’ several yr NS
NS
Marked improvement
Baruch et al. (23) (198s) Jaeckle and Dilsaver (24) ( 1986) Burke et al. (25) (1988)
6
NS
Depression
4 of 6 improved
1
59 yr old
Bipolar psychotic depression
7-15 ECT treatments 9 bilateral
Sustained with maintenance ECT 3-8 yr
Marked improvement
NS
3
Average age 71
Depression
5 unilateral
Much improved
Over I mo
72 yr old
6 unilateral 8 unilateral 12 bilateral
Marked improvement No change Marked improvement
12 days
1
Depression Depression Mania
2
Average age 63
Psychosis secondary to L-dopa and bromocriptine in both patients
6 bilateral
Rating scales used, moderate improvement
Over 6 mo
3 bilateral
Rating scales used, moderate improvement
Over 5 mo
Atre-Vdidya and Jampala (26) (1988) Hurwitz et al. (27) (1988)
Pre-L-dopa
each 7 treatments
NS
bilateral ECT
Marked improvement both in patient with mainly rigidity and patient with rigidity and tremor No unique benefit from ECT, “good control” with reinstitution of prior L-dopa dose No comment on PD symptoms One striking improvement, one moderate improvement, one little improvement PD signs reduced and temporarily relieved
Many months in both
NS
NS
NS NS
Bradykmesia and rigidity, greatly improved, tremor not affected, rating scale used Marked overall improvement, rating scales used Marked improvement
NS
Marked improvement in gait, speed, stability, rigidity, self-care; rating scale used Significant improvement with courses I and 2 ECT
3 days
Substantial improvement in gait, stability, speed, rigidity Rating scales used; PD marked improvement, TD markedly worse
Relapsed within 7 wk NS
Return of initial PD symptoms in spite of maintenance ECT Over 6 mo 1 wk, then no
significant PD with 2nd course and maintenance ECT Over 1 yr
Over 10 mo
(continued on foilowing page)
Movement Disorders, Vol. 6 , N o . 4 , 1991
R . FABER AND M . R . TRIMBLE
296
TABLE l-(Continued) Study Roth et al. (28) (1 988) Douyon et al. (29) (1989)
No. of patients 1
Patient history 62 yr old
I
Psychiatric morbidity
ECT parameters
Response duration
Results on PD
Manid and TD, both improved Depression
10 unilateral
Marked improvement
NS
7 bilateral
Rating scales used. 6 of 7 improved markedly in motor function
NS
No morbidity
NS
Excellent improvement in 5 of 5 with prominent rigidity and bradykinesia, no change in 3 of 3 with mainly Iremor, maximal response after 2-3 ECT courses Included in Balldin et al. (31) (1981) N o significant change, rating scale used
2-3 mo
Detailed ratings used, 5 marked improvement, 2 slight improvement, 2 no change Transient improvement
4 4 1 wk
No change with sham, 9 of 11 improved with real ECT
2-6 wk
Parkinsonism without psychiatric comorbidity Fromm (2) (1959)
Pre-r-dopa, PD of 5-20 yr’s duration
Balldin et al. (30) ( 1980) Ward et al. (32) (1980)
“On-off,” 2-7 yr
Bilateral
Average age 57, “on-off’ over 1 yr PD for 6-20 yr, “on-off’ for 2-7 yr
No morbidity
6 bilateral
No morbidity
3-8 bilateral
Berger and de Sot0 (34) ( 1990) Controlled studies
71 yr old
History of depresbion, mild dementia
6 unilateral
Anderson et al. (33) (1987)
Average age 70, 15 yr PD, “on-off’ 5 k 2 yr, on L-dopa
No morbidity
6 patients
Balldin et al. (31) (1981)
initially received sham ECT, then switched 4 to bilateral and 2 to unilateral; 5 received 5 6 bilateral initially
NS, not specified; TD, tardive dyskinesia.
peared” after three ECT treatments. Unfortunately, the authors did not indicate the duration of improvement or type of ECT. Yudofsky (18) described “marked improvement” in walking speed, postural stability, rigidity, selfcare, and manual dexterity as determined by rating scale assessment after 10 ECT treatments for delusional depression in a 66-year-old man. The patient experienced a sustained complete recovery from psychiatric symptomatology but his parkinsonian symptoms restarted in 3 days and in 1 week had returned to their pre-ECT level. Levy et al. (19) described a 76-year-old man with depression and PD who after 10 ECT treatments had substantially improved gait, speed, balance, and rigidity, which were maintained at 6-month follow-up observation. Holcomb et al. (20) administered 14 bilateral ECT treatments to a 72-year-old woman with delusional depression, PD, and coexisting tardive dyskinesia (TD). Marked improvements in depression and par-
Movement Disorders, Vol. 6 , No. 4, 1991
kinsonian symptoms were documented using rating scales, while the dyskinesias markedly worsened. Following the recurrence of PD and depression within 1 week, a second course of ECT again resolved these symptoms, which continued in remission with the administration of monthly maintenance ECT. Young et al. (21) described marked improvements in parkinsonian symptoms that persisted for over 1 year in a 73-year-old woman given seven unilateral ECT treatments for depression. This improvement was particularly notable since the depressive symptomatology went unchanged. The patient also evidenced moderately severe dementia, which remained unchanged over the period of study. Raskin (22) reported marked improvement in depression and complete resolution of idiopathic parkinsonism in a single patient that were both sustained by monthly maintenance ECT. Patient characteristics and ECT parameters were not specified.
ECT IN PARKINSON’S DISEASE Baruch et al. (23) described six patients with both depression and PD treated with ECT seven to 15 times. All had a good antidepressant response, while four of the six had notable improvement in their parkinsonism. Incredibly, at follow-up observation of 3-8 years, none of these four showed signs of PD or needed antiparkinsonian treatment. Jaeckle and Dilsaver (24) described a 59-year-old woman with a bipolar disorder who exhibited classic and severe symptoms of PD during several discrete depressive episodes. A course of nine bilateral ECT treatments brought about a remission of her psychotic depression and markedly improved her parkinsonian symptoms. Burke et al. (25) described treating three patients with coexisting PD and depression with ECT. All had remission from their depressive symptoms. One patient’s parkinsonism was much improved, another had marked improvement but the return of symptoms after 12 days, while the third patient’s parkinsonism remained unchanged. Atre-Vaidya and Jampala (26) described marked improvement of parkinsonism in a 72-year-old woman lasting over 10 months following 12 bilateral ECT treatments used to resolve a manic episode. Hurwitz et al. (27) successfully treated psychotic symptoms secondary to bromocriptine and L-dopa therapy with ECT in two PD patients. Rating scales revealed moderate improvement following ECT, which allowed the reinstitution of optimal doses of the medications. Roth et al. (28) described a 62-year-old man with coexistent mania, idiopathic parkinsonism, and TD. After a course of 10 right unilateral ECT treatments, his manic symptoms and TD remained unchanged, but all of his parkinsonian symptoms markedly improved. Douyon et al. (29) found ECT to improve depression and all aspects of PD in six of seven patients treated with an average of seven bilateral ECT treatments. Standardized rating instruments noted significant improvement in motor function after two ECT treatments. Final average ratings of impairment were 51% lower at the completion of ECT. Also of interest was the finding of a dissociation of antidepressant and antiparkinsonian effects in two of the patients. PARKINSON’S DISEASE WITHOUT PSYCHIATRIC COMORBIDITY Fromm’s report (2) on eight PD patients without psychiatric comorbidity noted that five of five patients with prominent rigidity and bradykinesia ob-
297
tained “noticeable remissions” (lasting 2-3 months) after two or three ECT treatments. Several bedridden patients became able to care for themselves and perform household duties for the first time in years. None of three patients with predominant tremor symptoms, including the only postencephalitic patient, responded substantially. Balldin et al. (30) reported the results of ECT given to five PD patients with prominent “on-off’ periods and without psychiatric comorbidity . These same five patients were included in a longer report on a total of nine PD patients with “on-off ’ symptoms and no significant psychiatric comorbidity , though a few patients were mildly depressed (31). Patients were given three to eight bilateral ECT treatments. Five of the nine showed marked improvement that lasted from 4-41 weeks. Their “off’ time decreased from 54 to 5% after ECT, with four of these five having no “off’ time after ECT. Two other patients had moderate improvement, with “off’ time decreasing from 52 to 26%, but their improvement was never marked and only lasted for 2 weeks. Finally, another two patients evidenced no improvement at all. Following the Balldin et al. (30) initial report, Ward et al. (32) reported on their experience in a similar patient population. They could detect no significant changes using rating scales in five PD patients without psychiatric comorbidity , each given six bilateral ECT treatments. They commented that these results ran counter to what had been their clinical experience. As an addendum, they described their results in a 57-year-old woman with PD and psychotic depression, both groups of symptoms improving significantly with three courses of ECT but eventually returning to former levels in spite of twice-weekly maintenance ECT. In 1987, Anderson et al. (33) did the first and only double-blind controlled study of ECT in PD. Again they observed patients with significant “off’ time and without psychiatric comorbidity or dementia. Six randomly assigned patients received five to six sham ECT treatments, identical to active treatment except that electric current was not given. Another five patients received five to six real bilateral ECT treatments. Striking differences were found in the percentage of “on” time, as the sham group remained unchanged but the active ECT group more than doubled its “on” time from 32 to 71%. Following their sham treatments, these six patients received real ECT, four patients bilaterally and two unilaterally. Their percentage of “on” time in-
Movement Disorders, Vol. 6, N o . #, 1991
R . FABER AND M . R . TRIMBLE
298
creased from 32 to 44%. Considering the effects of ECT on all 11 patients, two had marked improvement, seven had moderate improvement, and two did not have improvement. Of note was the short duration of improvement in light of the group’s prior report, ranging from only 2 to 6 weeks with a mean of just under 3 weeks in the nine responders. Berger and de Soto (34) described a 71-year-old man with severe PD and no evident psychopathologic condition who, during a course of six unilateral ECT treatments for his PD, had transient improvement after each treatment that quickly returned to baseline levels. DRUG-INDUCED PARKINSONISM In parallel with ECT improving idiopathic PD symptoms are reports of ECT ameliorating parkinsonism induced by neuroleptic drugs. Anath et al. (35) describe a 25-year-old schizophrenic man with catatonic symptoms refractory to fluphenazine, 6& 80 mglday. In the face of severe rigidity, tremor, and bradykinesia, a course of bilateral ECT was given, with marked improvement in both parkinsonism and psychopathology even as the fluphenazine was continued. Small et al. (36) found that patients treated with thiothixene plus ECT had fewer extrapyramidal symptoms (EPSS) than patients treated with thiothixene alone. Gangadhar et al. (37) assessed the effects of ECT on neuroleptic-induced parkinsonism in 17 nondepressed first-admission psychotic patients. Using the Simpson and Angus EPS rating scale, patients receiving over 500 chlorpromazine milligram equivalents and five ECT treatments obtained an average score of 1.0, which was significantly less than an average score of 5.5 from a well-matched control group of 18 patients who received equivalent medication without ECT for a similar duration. Goswani et al. (38) found that ECT significantly reduced the severity of neuroleptic-induced parkinsonism in nine schizophrenic patients observed in an A-B-A design: neuroleptics-neuroleptics plus nine bilateral ECT treatments for 3 weeksneuroleptics alone for 2 weeks. Parkinsonism scores declined steeply and significantly following the introduction of ECT, then increased gradually after completion of ECT. OTHER MOVEMENT DISORDERS Tardive Dyskinesia A number of case reports have described the effects of ECT on TD, with rather mixed results (39).
Movement Disorders, Vol. 6 , No. 4,1991
Asnis and Leopold (40) reported no effect from ECT on TD. They treated four women, each with TD and psychiatric decompensation. Blinded movement ratings of videotapes revealed no change in three patients and possible worsening in a fourth whose markedly fluctuating baseline ratings made conclusions tenuous. Price and Levin (41), however, reported nearly complete remission of TD in a 49-year-old woman given a course of seven ECT treatments, and Rosenbaum et al. (42) described a 74-year-old woman with recurrent agitated, depressive episodes who experienced a marked improvement of severe TD after a course of eight ECT treatments. Chacko and Root (43) reported dramatic remissions of severe TD in two women aged 62 and 63 years. Marked improvements began after their third and fourth ECT treatments and were sustained for 1- and 2-year follow-up examinations. The 62-yearold patient had, in addition, severe neuroleptic drug-induced EPSS of resting tremor, cogwheel rigidity, and akathisia, which all cleared concurrently with TD symptoms. Gosek and Weller (44) also described dramatic improvement in TD present for 5 years in a 54-yearold woman, when she was treated with ECT for a depressive episode. This improvement was sustained at follow-up observation 14 months later. Malek-Ahmadi and Weddige (45) described a remarkable reduction in dyskinetic movement in a 65year-old woman given five bilateral ECT treatments for depression with psychotic features. Tardive dyskinesia had been present for 10 years before ECT, but at 2-month post-ECT follow-up observation, only minimal, infrequent buccolingual movements were present. Based on a community survey in Hungary, Gardos et al. (46) noted a very low prevalence of TD in outpatient schizophrenics there. They speculated that the preferred practice of using ECT in place of high-dosage neuroleptics may have a protective effect in the development of TD. However, in a survey of 682 mental hospital patients of whom 196 had buccal-lingual-masticatory (tardive) dyskinesias, Brandon et al. (47) found no association between ECT exposure or number and the occurrence of TD. Other authors have suggested that ECT may contribute to the development of or exacerbate TD. Uhrbrand and Faurbye (48) ascribed four cases of TD to the administration of ECT. These were drawn from 33 cases of TD in a total psychiatric
ECT IN PARKINSON’S DISEASE population of 500 women. The extent of ECT given to the entire study population was not described, basing the ECT-TD relationship solely on the appearance of TD after the administration of ECT. Holcomb et al. (20), in their case report of a 72year-old man with a delusional depression, described marked worsening of TD while depressive and PD symptoms greatly improved with a course of ECT. Flaherty et al. (49) described three cases of reversible buccolingual dyskinesia emerging during the course of ECT without concurrent or recent neuroleptic drug administration. The dyskinesia lasted in each respective case for 3 months, 2 weeks, and 4 weeks. In their case report of coexisting mania, PD, and TD, Roth et al. (28) found ECT to alleviate PD and manic symptoms, with choreoathetoid limb movements resolving while severe orofacial and lingual dyskinesias appeared. Fahn et al. (50) described ECT relieving severe, intractable tardive akathisia and TD in three patients. These mixed reports of ECT sometimes ameliorating and sometimes worsening TD would suggest heterogeneity in the underlying biochemical pathophysiology of TD. Other Conditions We could find only two case reports of tardive dystonia treated with ECT. Kwentus et al. (51) described a 52-year-old woman with extensive prior neuroleptic exposure who exhibited sustained opisthotonic trunk extension with retrocollis and sustained extension movement of the arms. The patient received a course of nine nondominant, unilateral ECT treatments for catatonia associated with depression. Along with completely relieving all depressive symptoms, the dystonias abated except for some hyperextension of the wrists. Adityanjee et al. (52) described a 30-year-old man with a history of schizophrenia treated with antipsychotic drugs since age 17. He began a course of ECT after a I-month history of severe anterocollis. Auditory hallucinations disappeared after four treatments while the tardive dystonia began to improve after six ECT treatments. After 11 treatments, the dystonia was remarkably improved. At 2-month followup observation, there was a moderate recrudescence of the dystonia. In a mental hospital survey, Friedman et al. (53) suggested that ECT may be a risk factor for the emergence of tardive dystonia, as two of the five patients they identified as having tardive dystonia
299
were previously treated with ECT. They do not, however, report the percentage of patients without tardive dystonia (n = 326) who had received ECT. They present no statistical basis for their conclusion. Araneta et al. (54) described a case of Gilles de la Tourette’s syndrome in a man with symptom onset at age 35. After neuroleptics no longer provided relief for severe symptomatology, a course of ECT was administered, to no avail. In a report on the use of ECT in one child and three adolescents, Guttmacher and Cretella (55) described a 15-year-old boy with Gilles de la Tourette’s syndrome and childhood-onset pervasive developmental disorder. Though a course of seven bilateral ECT treatments brought about a dramatic improvement in a concurrent mood disorder, this was not accompanied by any change in motor and speech functioning. Swerdlow et al. (56) described a 65-year-old man with a disabling tic and a major depressive episode. The patient’s motor and affective symptoms resolved after ECT, and he remained asymptomatic at 1-year follow-up observation. Transient bilateral upper limb asterixis lasting for 2 h was noted after two of 10 ECT treatments given to a 48-year-old woman treated for mania and later found to have primary hyperparathyroidism (57). MECHANISM OF ACTION A suggested mechanism for the efficacy of ECT in PD has been discussed by Fochtmann (58) with an emphasis on the effects of electroconvulsive shock (ECS) on animal dopamine systems. Nomikos et al. (50) found massive increases in interstitial striatal dopamine using dialysis probes in freely moving rats given ECS. Long-term (as opposed to short-term) ECS enhances a variety of dopaminemediated behaviors stimulated by apomorphine, amphetamine, or L-dopa plus tranylcypromine (6062). Costain et al. (63) found ECT in depressed patients to increase the growth hormone response to apomorphine. Though Chiodo and Antelman (64) found progressive dopamine autoreceptor subsensitivity independent of repeated treatment after ECS, the dopaminergic effects of ECS have been suggested to occur at least postsynaptically (65) or even further downstream of the receptor at its effector-coupled system (66). Recent work suggests prominent ECS effects on D, receptors (67). Sershen et al. (68) found ECS to significantly increase D, binding activity in control and MPTP-treated mice without affecting D, receptor activity. Sharp
Movement Disorders, Vol. 6, No. 4, 1991
300
R . FABER AND M . R . TRIMBLE
et al. (69) found ECS-enhanced behavior with the D, (SFK38393) and mixed (apomorphine) dopamine agonists but not with a specific D, agonist (RU24213). While Fochtmann et al. (70) found increased D, receptor binding in the substantia nigra of rats after long-term ECS, Martin et al. (71) found no such ECS effect and Klimek and Neilson (72) detected a decrease in D, binding sites in the nucleus accumbens. In addition to these findings regarding D, receptor binding, striatal binding of the D, receptor ligand, spiperone, is also affected by ECS (73-76). The physiological relationship of D, and D, receptors is such that D, receptor activation is required to obtain full expression of the D, receptor site, which has typically been associated with the clinical benefits of dopaminergic therapy in PD (77-80). An up-regulation of D, receptors is thus proposed as a mechanism for the antiparkinsonian effect of ECT. Nondopaminergic systems affected in PD may also be modified by ECT. In PD the ascending noradrenergic ceruleocortical system is reduced by about 50% (81) while, as an apparent compensation, cortical beta,-adrenergic receptors are increased (82). Repeated ECS down-regulates the cortical beta-adrenoreceptor number (83), a phenomenon it shares with all known effective antidepressant treatments but without known direct relevance on motor systems. Changes in brain gamma-aminobutyric acid (GABA) in PD are debated. While reductions in GABAergic systems have been reported, this may simply be secondary to loss of GABA-sensitive dopaminergic nigrostriatal neurones (81). Striatal GABA concentrations are increased by ECS (84) and GABA-B receptors have been reported to increase with repeated ECS (85). The findings that D, receptors are located presynaptically on striatal GABAergic neurons (86) could link both dopamine and GABA systems to the antiparkinsonian effect of ECT. Although serotoninergic systems are moderately reduced in PD, these changes are not believed to be related to parkinsonian symptoms (81). Electroconvulsive shock reduces serotonin- 1A presynaptic receptors and up-regulates serotonin-2 postsynaptic receptors (87); these changes are believed to be extremely relevant in mediating antidepressant effects (88,89). Although cholinergic systems are mainly intact in the basal ganglia in PD, cortical and hippocampal cholinergic systems are diminished to varying de-
Movement Disorders, Vol. 6,N o . 4, 1991
grees. This latter diminishment in cholinergic systems may contribute to the cognitive dysfunction that can be associated with PD. Dopamine and cholinergic links have historically been a major avenue for therapeutic interventions in PD. Electroconvulsive shock induces a small downregulation in cortical muscarinic cholinergic receptors (90). Various peptides are reduced in PD, but none of these deficiencies correlates with parkinsonian symptoms or response to treatment. Electroconvulsive shock can increase encephalin concentration, but no consistent peptide changes have been reported in this little-studied area (91). In discussing the role of glutamate in the basal ganglia, Suedfeld et al. (92) proposed that ECT benefits PD by decreasing glutamatergic function. Summarized in Table 2, various neurotransmitter systems are perturbated in PD, and repeated ECS/ ECT causes many neuroadaptive responses. It is ECT’s effect on increasing postsynaptic dopamine function that seems most relevant to its antiparkinsonian action. This effect would also explain the exacerbation of TD in some reports. The more consistent results of ECT on PD in comparison with the other movement disorders reviewed emphasize the differences in the underlying biochemistry of the various disorders. DISCUSSION This review of the literature suggests that ECT has antiparkinsonian effects, independent of any effects on mental state. The predictability, magniTABLE 2. Neurotransmitters in ECT and PD PD Dopamine
Decreased 80%
D1 D2
Norepinephrine GABA
Decreased but beta, receptors increased Decreased
Serotonin
Decreased
Acetylcholine
Minimal changes, decrease in cortical and hippocampal systems
ECT Increased receptor responsiveness Increased receptor activation Increased receptor binding, apomorphine-growth hormone enhancement, apomorphine-prolactin reduction Decreased beta, receptors Concentration increased, receptors increased S-HT,, presynaptic receptors decreased, 5-HT, postsynaptic receptors increased Minimal changes, slight downregulation of cortical mucarinic receptors
ECT, electroconvulsive therapy; PD, Parkinson’s disease.
ECT IN PARKINSON’S DISEASE tude, and duration of such effects, however, cannot be well specified. The reports have largely been poorly controlled, unblinded, with failure to attempt objective assessment of PD symptoms. Nonetheless, several studies are substantially better designed, including the Anderson et al. (33) double-blind sham-controlled study. It is on the basis of these data that we offer these conclusions. This review examines the results of 27 reports on 78 patients with idiopathic PD. We tabulate that 48 patients obtained definite, meaningful clinical benefit sustained for at least 2 weeks while 30 did not. While most of the reports we cite have been retrospective and undoubtedly the literature is biased by the underreporting of negative cases, three prospective studies (29,32,33) cumulatively found improvement in 15 of 23 patients. We speculate that approximately half of PD patients who receive ECT may be expected to benefit clinically. This is aside from the 80% response rate expected when treating depression or psychosis. Such responses are certainly worthy of further investigation. We counted four of eight unilaterally treated patients positively, in contrast to 44 of 70 patients with bilateral treatments. Given the notable difference in cognitive side effects between those electrode placements (92) and the problems of cognitive dysfunction in PD, further study of electrode position is warranted. The length of treatment and timing of ECTs requires exploration. The onset of antiparkinsonian ECT effects varies considerably from rather immediate to requiring a “full course” of between six and 10 treatments. While the distinction of improvement sustained for more than 2 weeks is more valid clinically at this point, transient improvement noted by Yudofsky (18) and Burke et al. (25) implies that neurochemical changes are induced that, if they could be harnessed and prolonged, would also be therapeutically meaningful. Several authors (20,22) have advocated maintenance ECT in PD, as is sometimes used in severe relapsing affective disorders. We would suggest that PD patients who have an unsatisfactory response to conventional treatments be considered for a course of up to eight bilateral ECT treatments given two to three times per week. The literature on unilateral ECT for PD is too scanty to recommend it at this time. If the transient confusion and amnesia from bilateral ECT become major problems, spacing the treatments further apart usually reduces such side effects to acceptable levels. If ECT brings about clinically
301
significant improvement that lasts at least 1 month, we would continue maintenance ECT at about monthly intervals. Our review also suggests a role for ECT in the management of drug-induced parkinsonism (93) and TD. The judicious combination of ECT with neuroleptics may cause fewer motor side effects than neuroleptics alone and for some patients may also be more efficacious (94). Other drug-induced movement disorders have not been studied sufficiently to warrant comment. In summary, though the literature we reviewed is more notable for its quantity than its quality, we conclude that approximately half of patients with severe PD might be expected to have a meaningful clinical response of sufficient duration to make ECT a worthwhile adjunctive consideration when current therapies are unsatisfactory, especially if maintenance ECT can be continued when warranted. Acknowledgment: We are grateful to Dr. Eileen Smith for reviewing and editing this manuscript and thank Ann Martin and Joanna McNamara for expert manuscript preparation.
REFERENCES 1. Gallinek A. Electric convulsive therapy in geriatrics. NY
State J Med 1947;47:1233-1241. 2. Fromm GH. Observations of the effect of electroshock treatment on patients with parkinsonism. Bull Tulane Univ Med Faculty 1959;18:71-73. 3. Kalinowsky LB. Die Electrokrampfbehandlungin ihrer Beziehung zur Neurologie. Monatsschr Psychiatr Neuroll949; 177:268-279. 4. Kaplan LA, Freund DJ. Electroshock therapy in patients with severe organic disease. I / / Med J 1949;95:96-101. 5. Savitsky N , Karliner W. Electroshock in the presence of organic disease of the central nervous system. J Hillside HOSP 1953;2:3-22. 6. Shapiro MF, Goldberg HH. Electroconvulsive therapy in patients with structural disease of the central nervous system. Am J Med Sci 1957;233:186-195. 7. Ehrenberg R, Gullingsrud MJO. Electroconvulsive therapy in elderly patients. Am J Psychiatry 1955;111:743-747. 8. Wolff GE. Electric shock treatment. Am J Psychiatry 1955; 1 1 1 :748-750. 9. Tucker WI, Fleming R, Raeder 0 . Electroconvulsive treatment in a general hospital. N Engl J Med 1955;253:451-454. 10. Lebensohn ZM, Jenkins RB. Improvement of parkinsonism in depressed patients treated with ECT. Am J Psychiatry 1975;132:283-285. 11. Lipper S, Bermanzohn PC. Electroconvulsive therapy in patients with parkinsonism. Am J Psychiatry 1975;132:457. 12. Brown GC. Parkinsonism, depression and ECT. Am J Psychiatry 1975;132:1084. 13. Lebensohn ZM. Parkinsonism, depression and ECT. Am J Psychiatry 1975;132:1084. 14. Rainey JM, Faust M. Parkinsonism masked by ECT and psychotropic medication. Am J Psychiafry 1975;132:10841085.
Movement Disorders, Vol. 6 , No. 4, 1991
302
R . FABER AND M . R . TRIMBLE
15. Dysken M, Evans HM, Chan CH, et al. Improvements of depression and parkinsonism during ECT. Neuropsychobiology 1976;2:81-86. 16. Asnis G. Parkinson’s disease, depression, and ECT: a review and case study. A m J Psychiatry 1977;134:191-195. 17. Barcia D, Martinez PF. Cuadros depresivos en enfermedad de Parkinson tratados con electroshock. Arch Neurobiol 1978;41:393-398. 18. Yudofsky SC. Parkinson’s disease, depression, and electroconvulsive therapy: a clinical and neurological synthesis. Compr Psychiatry 1979;20:579-581. 19. Levy LA, Savit JM, Hodes M. Parkinsonism: improvement by electroconvulsive therapy. Arch Phys Med Rehabil 1983; 64:432433. 20. Holcomb HH, Sternberg DE, Heninger GR. Effects of electroconvulsive therapy on mood, parkinsonism, and tardive dyskinesia in a depressed patient: ECT and dopamine systems. Biol Psychiatry 1983;18:865-873. 21. Young RC, Alexopoulos GS, Shamoian CA. Dissociation of motor response from mood and cognition in a parkinsonian patient treated with ECT. Biol Psychiatry 1985;20:566-569. 22. Raskin D. Can ECT cure Parkinson’s disease? 138th Annual Meeting of the American Psychiatric Association. Abstracts of the New Research Program. Dallas: TX, 1985. 23. Baruch P, Jouvent R, Vindreau C, Drouillon C, Widlocher D, Agid Y . Improvements of parkinsonism in ECT-treated depressed patients: Parkinson’s disease and depressionrelated extra-pyramidal disorder? In: Abstracts of the IVth World Congress of Biological Psychology. Philadelphia: PA, 1985. 24. Jaeckle RS, Dilsaver SC. Covariation of depressive symptoms, parkinsonism, and post-dexamethasone plasma cortical levels in bipolar patients: simultaneous response to ECT and lithium carbonate. Acta Psychiatr Scand 1986;74:68-72. 25. Burke WJ, Peterson J, Rubin EH. Electroconvulsive therapy in the treatment of combined depression and Parkinson’s disease. Psychosomatics 1988;29:341-346. 26. Atre-Vaidya N, Jampala VC. Electroconvulsive therapy in parkinsonism with affective disorder. Br J Psychiatry 1988; 152:55-58. 27. Hunvitz TA, Calne DB, Waterman K. Treatment of dopaminomimetic psychosis in Parkinson’s disease with electroconvulsive therapy. Can J Neurol Sci 1988;15:32-34. 28. Roth SD, Mukherjee S, Sacheim HA. Electroconvulsive therapy in a patient with mania, parkinsonism, and tardive dyskinesia. Convulsive Ther 1988;4:92-97. 29. Douyon R, Serby M, Klutchko B, Rotrosen J. ECT and Parkinson’s disease revisited: a “naturalistic” study. Am J Psychiatry 1989;146:1451-1 455. 30. Balldin J, Eden S, Granerus AK, et al. Electroconvulsive therapy in Parkinson’s syndrome with “on-off’ phenomenon. J Neural Transm 1980;47:11-21. 31. Balldin J, Granerus AK, Lindstedt G, Modigh K, Wallinder J. Predictors for improvement after electroconvulsive therapy in a parkinsonian patient with “on-off’ symptoms. J Neural Transm 1981;52:199-21 1. 32. Ward C, Stem GM, Pratt RTC, McKenna P. Electroconvulsive therapy in parkinsonian patients with the “on-off” syndrome. J Neural Transm 1980;49:133-135. 33. Anderson K, Balldin J, Gottpries CG, et al. A double-blind evaluation of electroconvulsive therapy in Parkinson’s disease with “on-off’ phenomena. Acta Neurol Scand 1987; 76:191-199. 34. Berger M, de Soto DA. The use of ECT for parkinson symptoms in a nondepressed patient. Psychosomatics 1990;31: 465466.
Movement Disorders. Vol. 6, N o . 4, 1991
35. Anath J, Samra D, Kolivakis T. Amelioration of druginduced parkinsonism by ECT. A m J Psychiatry 1979;136: 1094. 36. Small JG, Milstein V, Klapper M, Kellams JJ, Small IF. ECT combined with neuroleptics in the treatment of schizophrenia. Psychopharmacol Bull 1982;18:34-35. 37. Gangadhar BN, Roychowdhury J, Channabasavanna SM. ECT and drug-induced parkinsonism. Indian J Psychiatry 1983;25:212-2 13. 38. Goswani U, Duttaq S, Kuruvilla K, Papp E, Perengi A. Electronconvulsive therapy in neuropeptic-induced parkinsonism. Biol Psychiatry 1989;26:234-238. 39. Hay DP, Hay L, Blackwell B, Spiro HR. ECT and tardive dyskinesia. J Geriatr Psychiatry Neurol 1990;3:106-109. 40. Asnis GM, Leopold MA. A single-blind study of ECT in patients with tardive dyskinesia. Am J Psychiatry 1978;135: 1235-1238. 41. Price TRP, Levin R. The effects of electroconvulsive therapy on tardive dyskinesia. Am J Psychiatry 1978;135:991993. 42. Rosenbaum AH, O’Connor MK, Duane DD, Auger RG. Treatment of tardive dyskinesia in an agitated, depressed patient. Psychosomatics 1980;21:765-766. 43. Chacko RC, Root L. ECT and tardive dyskinesia: two cases and a review. J Clin Psychiatry 1983;44:265-266. 44. Gosek E, Weller RA. Improvement of tardive dyskinesia associated with electroconvulsive therapy. J Nerv Men1 Dis 1988;176:120-122. 45. Malek-Ahmadi P, Weddige RL. Tardive dyskinesia and electroconvulsive therapy. Convulsive Ther 1988;4:328-331. 46. Gardos G, Samu I, Kallos M, Cole JO. Absence of severe tardive dyskinesia in Hungarian schizophrenic outpatients. Psychopharmacology 1980;71:29-34. 47. Brandon S, McClelland HA, Protheroe C. A study of facial dyskinesia in a mental hospital population. Br J Psychiatry 1971;118:171-184. 48. Uhrbrand L, Faurbye A. Reversible and irreversible dyskinesia after treatment with perphenazine, chloropromazine, reserpine, and electroconvulsive therapy. Psychopharmacologin 1960;1 :40W18. 49. Flaherty JA, Naidu J, Dysken M. ECT, emergent dyskinesia, and depression. Am J Psychiatry 1984;141:808-809. 50. Fahn S, Brin M, Bressman S. Relief of intractable, disabling tardive akathisia and tardive dyskinesiddystonia with electroconvulsive therapy (ECT) [Abstract]. American Neurological Association Meeting, September 1989. New Orleans: LA, 1989. 51. Kwentus JA, Schulz SC, Hart RP. Tardive dystonia, catatonia, and electroconvulsive therapy. J Nerv Ment Dis 1984; 172: 171-173. 52. Adityanjee, Jayaswal SK, Chan TM, Subramaniam M. Temporary remission of tardive dystonia following electroconvulsive therapy. Br J Psychiatry 1990;156:433435. 53. Friedman JH, Kucharski LT, Wagner RL. Tardive dystonia in a psychiatric hospital. J Neurol Neurosurg Psychiatry 1987;50:801-803. 54. Araneta E, Magen J, Musci MN, Singer P, Vann CR. Gilles de la Tourette’s syndrome-symptom onset at age thirtyfive. Child Psychiatry Hum Dev 1975;5:224230. 5 5 . Guttmacher LB, Cretella H. Electroconvulsive therapy in one child and three adolescents. J Clin Psychiatry 1988;49: 20-23. 56. Swerdlow NR, Gierz M, Berkowitz A, Nemiroff R, Lohr J. Electroconvulsive therapy in a patient with severe tic and major depressive episode. J Clin Psychiatry 1990;51:3435. 57. Dysken MW, Halaris AE. Post-ECT asterixis associated
ECT IN PARKINSON'S DISEASE with primary hyperparathyroidism. Am J Psychiatry 1978; 135:1237-1238. 58. Fochtmann L. A mechanism for the efficiency of ECT in Parkinson's disease. Convulsive Ther 1988;4:321-327. 59. Nomikos GG, Zis AP, Damsma G, Fibiger HC. Electroconvulsive shock produces large increases in interstitial concentrations of dopamine in the rat straitum: an in vivo microdialysis study. Neuropsychopharmacology 1991;4:65-69. 60. Modigh K, Balldin J, Eriksson E, Granerus AK, Walinder J. Increased responsiveness of dopamine receptors after ECT: a review of experimental and clinical evidence. In: Lerer B, Weiner RD, Belmaker RH, eds. ECT: basic mechanisms. London: John Libby, 1984:18-27. 61. Green AR, Nutt DJ. Psychopharmacology of repeated seizures: possible relevance to the mechanism of action of electroconvulsive therapy. In: lverson LL, Iverson SD, Snyder SH, eds. Handbook of psychopharmacology. Vol. 19. New York: Plenum Press, 1987:375419. 62. Lerer B. Neurochemical and other consequences of ECT. Implications for the pathogenesis and treatment of affective disorders. In: Meltzer HL, ed. Psychopharmacology: the third generation of progress. New York: Raven Press, 1987:577-588. 63. Costain DW, Cowen PJ, Gelder MG, Grahame-Smith DG. Electroconvulsive therapy and the brain: evidence for increased dopamine-mediated responses. Lancet 1982;2:400404. 64. Chiodo LA, Antelman SM. Electroconvulsive shock: progressive dopamine autoreceptor subsensitivity independent of repeated treatment. Science 1980;210:799-801. 65. Green AR, Heal DJ, Grahame-Smith DG. Further observations on the effect of repeated electroconvulsive shock on the behavioural responses of rats produced by increases in the functional ability of brain 5-hydroxytryptamine and dopamine. Psychopharmacology 1977$2: 195-200. 66. Heal DJ, Green AR. Repeated electroconvulsive shock increases the behavioral responses of rats to injection of both dopamine and dibutyryl cyclic AMP into the nucleus accumbens. Neuropharmacology 1978;17:1085-1087. 67. Nowak G, Zak J. Repeated electroconvulsive shock (ECS) enhances striated D-1 dopamine receptor turnover in rats. Eur J Pharmacol 1989;167:307-308. 68. Sershen H, Wolinsky T, Douyon R, et al. The effects of electroconvulsive shock on dopamine-1 and dopamine-2 receptor ligand binding activity in MPTP-treated mice. J Neuropsychiatry Clin Neurosci 1991;3:58-63. 69. Sharp T, Kingston J, Grahame-Smith DG. Repeated ECS enhances dopamine D-1 but not D-1 agonist-induced behavioral responses in rats. Psychopharmacology 1990;lOO: 110-1 14. 70. Fochtmann LJ, Cruciani R, Aiso M, Potter WZ. Chronic electroconvulsive shock increases D-1 receptor binding in rat substrantia nigra. Eur J Pharmacol 1989;167:305-306. 71. Martin WR, Sloessl AJ, Palmer M, et al. Pet scanning in dystonia. Adv Neurol 1988;50:223-229. 72. Klimek V, Neilson M. Chronic treatment with antidepressants decreases the number of 3H-SCH23390 binding sites in the rat striatum and limbic system. Eur J Pharmacol 1987; 139: 163-169. 73. Bergstrom DA, Kellar KJ. Effect of electroconvulsive shock on monoaminergic receptor binding sites in rat brain. Nature 1979;278:464-466. 74. Deakin JF, Owen F , Cross AJ, Dashwood MJ. Studies on possible mechanisms of action of electroconvulsive therapy; effects of repeated electrically induced seizures on rat brain receptors for monoamines and other neurotransmitters. Psychopharrnacology 1981;73:345-349. 75. Lerer B, Belmaker RH. Receptors and mechanism of action
303
of electroconvulsive therapy. Biol Psychiatry 1982;17:497511. 76. Gulati A, Srimai RC, Dhawan KN, Dhawan BN. On the mechanism of potentiation of apomorphine-induced stereotypy due to electroconvulsive shock. Neuropharmacology 1987;26:1733-1737. 77. Beaulieu M. Clinical importance of D-1 and D-2 receptors. Can J Neurol Sci 1987;14:402406. 78. Clark D, White FJ. Review: DI dopamine receptor-the search for a function: a critical evaluation of the DUD2 dopamine receptor classification and its functional implications. Synapse 1987;1:347-388. 79. Creese I. Biochemical properties of CNS dopamine receptors. In: Meltzer HL, ed. Psychopharmcology: the third generation of progress. New York: Raven Press, 1987:257264. 80. Nomikos GG, Zis AP, Damsma G, Fibiger HC. Electroconvulsive shock and dopamine neurotransmission [Abstract]. Biol Psychiatry 1990;27:143A. 81. Agid Y , Javoy-Agid F, Ruberg M. Biochemistry of neurotransmitters in Parkinson's disease. In: Marsden CD, Fahn S, eds. Movement disorders 2. London: Butterworths, 1987: 166-230. 82. Cash R, Ruberg M, Raisman R, Agid Y . Adrenergic receptors in Parkinson's disease. Brain Res 1984;322:269-275. 83. Belmaker RH, Lerer B, Bannet J, Birmaker B. The effect of electroconvulsive shock at a clinically equivalent schedule on rat cortical beta-adrenoreceptors. J Clin Pharmacol 1982;34:275. 84. Green AR, Sant K, Bowdler JM, Cowen PJ. Further evidence for a relationship between changes in GABA concentration in rat brain and enhanced monoamine activated behaviours following repeated electroconvulsive shock. Neuropharmacology 1982;21:981-984. 85. Lloyd KG, Perrault G, Zivkovic B. Implications of GABAergic synapses in neuropsychiatry. J Pharmacol 1985; 16(suppl 2):5-27. 86. Porceddu ML, Giogi 0, Ongini E, Mele S , Biggio G. 3H SCH23390 binding sites in the rat substantia nigra: evidence for a presynaptic localization and innervation by dopamine. Life Sci 1986;39:321-328. 87. Green AR, Johnson P, Nemgaunkar VL. Increased 5-HT receptor number in the brain as a probable explanation for behaviour folthe enhanced 5-hydroxytryptamine-mediated lowing repeated electroconvulsive shock administration to rats. Br J Pharmacol 1983;80: 173-177. 88. Grahame-Smith DG, Green AR, Costain DW. Mechanism of the antidepressant action of electroconvulsive therapy. Lancet 1978;1:25&257. 89. Lerer B, Shapira B. Neurochemical mechanisms of mood stabilization: focus on electroconvulsive therapy. Ann N Y Acad Sci 1985;462:366-375. 90. Lerer B, Sitaram N. Clinical strategies for evaluating electroconvulsive therapy mechanisms-pharmacological, biochemical and psychophysiological approaches. Prog Neuropsychopharmacol Biol Psychiatry 1983;7:309-333. 91. Holaday JW, Belenky GL. Opiate-like effects of electroconvulsive shock in rats: a differential effect on nociceptive measures. Life Sci 1980;27:1929-1938. 92. Suedfeld P, Ramirez CE, Remick RA, Fleming JA. Reduction of post-ECT memory complaints through brief, partial restricted environmental stimulation. Prog Neuropsychopharmacol Biol Psychiatry 1989;13:693-700. 93. Fink M. ECT for Parkinson's disease? Convulsive Ther 1988;4: 189-19 1. 94. Greenberg LB, Mofson K, Fink M. Prospective electroconvulsive therapy in a delusional depressed patient with a frontal meningioma. Br J Psychiatry 1988;153:105-107.
Movement Disorders, Vol. 6,No. 4, 1991
