Directory UMM :Data Elmu:jurnal:B:Biological Psichatry:Vol48.Issue3.2000:

Effects of Stimulus Intensity on the Efficacy of
Bilateral ECT in Schizophrenia: A Preliminary Study
Worrawat Chanpattana, M.L. Somchai Chakrabhand, Wanchai Buppanharun,
and Harold A. Sackeim
Background: This preliminary study examined the effects
of electrical stimulus intensity on the speed of response
and efficacy of bilateral electroconvulsive therapy (ECT)
in the treatment of schizophrenia.
Methods: Sixty-two patients with schizophrenia received
combination treatment with bilateral ECT and flupenthixol. Using a randomized, double-blind design, the
effects of three dosages of the ECT electrical stimulus
were examined. Patients were treated with a stimulus
intensity that was just above seizure threshold, two-times
threshold, or four-times threshold. Assessments of outcome used the Brief Psychiatric Rating Scale, Global
Assessment of Functioning, and the Mini-Mental State
Exam.
Results: Thirty-three of sixty-two patients met remitter
criteria, including maintaining improvement over a
3-week stabilization period. The dosage groups were
equivalent in the number of patients who met remitter
criteria. The low-dose remitter group (n 5 11) received

more ECT treatments and required more days to meet
remitter status than both the twofold (n 5 11) and fourfold
remitter groups (n 5 11). There was no difference among
the groups in change in global cognitive status as assessed
by the Mini-Mental State Exam.
Conclusions: This preliminary study indicates that treatment with high-dosage bilateral ECT speeds clinical response in patients with schizophrenia. There may be a
therapeutic window of stimulus intensity in impacting on the
efficacy of bilateral ECT, which needs further study. A more
sensitive battery of cognitive tests should be used in future
research. Biol Psychiatry 2000;48:222–228 © 2000 Society of Biological Psychiatry
Key Words: Electroconvulsive therapy, method, efficacy,
schizophrenia

From the Departments of Psychiatry (WC) and Preventive Medicine (WB),
Srinakharinwirot University, Bangkok, and the Department of Mental Health,
Nonthaburi (MLSC), Thailand, and the Department of Biological Psychiatry,
New York State Psychiatric Institute and Departments of Psychiatry and
Radiology, College of Physicians & Surgeons, Columbia University, New
York, New York (HAS).
Address reprint requests to Worrawat Chanpattana, M.D., Department of Psychiatry, Srinakharinwirot University, 681Samsen, Dusit Bangkok 10300, Thailand.

Received October 1, 1999; revised January 10, 2000; accepted January 19, 2000.

© 2000 Society of Biological Psychiatry

Introduction

S

ince its inception, electroconvulsive therapy (ECT) has
been used to treat schizophrenia. Neuroleptic medications rapidly replaced ECT after their introduction in the
1950s. During the 1970s, when limitations in the efficacy
of neuroleptics and adverse effects from prolonged use
were recognized, interest in ECT as a treatment for
medication-resistant schizophrenia returned (Fink and
Sackeim 1996). A number of surveys in several countries
found that from 2.9% to 36% of patients receiving ECT
had a diagnosis of schizophrenia (Krueger and Sackeim
1995). This rate was reported to be 60% and 75% in Czech
(Baudis 1992) and Indian patients (Shukla 1981),
respectively.

Research on the use of ECT in schizophrenia has
been characterized by a variety of methodologic limitations, including uncertain diagnostic criteria, nonrandom assignment to treatment groups, and lack of blind
and reliable clinical assessment (Krueger and Sackeim
1995). Nonetheless, the conclusions suggested in this
literature are that 1) ECT is effective in the treatment of
schizophrenia, especially among patients with acute
exacerbations, relatively short duration of illness, or
both; and that 2) combined ECT and neuroleptic treatment is more effective than either ECT alone or
neuroleptic treatment alone (Chanpattana et al 1999a,
1999b; Fink and Sackeim 1996).
The interactive effects of stimulus intensity and electrode placement on the efficacy of ECT in major depression is established (Sackeim et al 1987a, 1987b, 1993, in
press; Krystal et al 1998; McCall et al, in press). With
right unilateral ECT, the likelihood of clinical response in
major depression is highly dependent on the degree to
which stimulus dosage exceeds seizure threshold. With
both right unilateral and bilateral ECT, higher stimulus
intensity results in faster clinical improvement ( Nobler et
al 1997; Sackeim et al 1993, in press). The impact of
electrical dosage in moderating the efficacy of bilateral
ECT in schizophrenia is unknown. We hypothesized that

high-dosage bilateral ECT would enhance the speed of
clinical response in patients with schizophrenia.
0006-3223/00/$20.00
PII S0006-3223(00)00830-1

ECT Stimulus Intensity

Methods and Materials
Subjects
Sixty-seven patients (30 men, 37 women) with acute psychotic
exacerbations and who met the DSM-IV criteria for schizophrenia (American Psychiatric Association 1994) were referred for
ECT because of failure to respond to neuroleptic treatment.
Psychiatric diagnosis was based on the consensus of three
psychiatrists and also had to concur with the patients’ medical
records. Diagnosis in the medical records had to be consistent
throughout the episode of illness. Other inclusion criteria were a
minimum pretreatment score of 37 on the Brief Psychiatric
Rating Scale (BPRS, 18 items, rated 0 – 6; Overall and Gorham
1962), and subjects had to be between ages 16 and 50 years.
Patients were excluded if they received treatment with depot

neuroleptics or ECT during the previous 6 months, psychotic
disorders due to a general medical condition, neurologic illness,
alcohol or other substance abuse, or serious medical illness. All
patients had normal results of complete blood count, serum
electrolytes, and electrocardiography. This study was approved
by the Ethics Committee of the Faculty of Medicine of Srinakharinwirot University and the National Review Board of Research Studies in Humans of Thailand. After complete description of the study and the opportunity to ask questions, voluntary
written informed consent was obtained from the patients or their
guardians.
Twenty-three patients (10 men, 13 women) were randomized
to receive low-dosage bilateral ECT (dose just above the seizure
threshold), 23 patients (11 men and 12 women) were assigned to
the twofold seizure threshold group, and 21 patients (9 men and
12 women) were assigned to the fourfold seizure threshold
group. Five patients dropped out from this double-blind comparative study—two from the low-dose group, two from the twofold
seizure threshold group, and one from the fourfold seizure
threshold group—leaving 62 patients in the study.

Procedures
Neuroleptic medications prescribed before the study were discontinued without a washout period. Flupenthixol was started
before the first ECT session and was continued throughout the

study. The dosage schedule of flupenthixol was fixed at 12
mg/day ($600 mg chlorpromazine [CPZ] equivalents) during the
first week, 18 mg/day ($900 mg CPZ equivalents) for the days
8 –10, and 24 mg/day ($1200 mg CPZ equivalents) thereafter,
depending on tolerability. All patients were treated between
18 –24 mg/day of flupenthixol, which has a half-life of approximately 35 hours, leading to steady state at 7 days. Benzhexol
(4 –15 mg/day) was used to manage extrapyramidal symptoms,
with dosage titrated on a clinical basis. Diazepam (10 mg/day)
was prescribed to control agitation on a PRN basis and was
withheld at least 8 hours before each ECT treatment.
Electroconvulsive therapy was administered three times per
week. The ECT devices were a Thymatron DGx and MECTA SR
1. Each patient was treated with only one ECT device (two
different hospitals participated in the study, each using a different
device). Thiopental (2– 4 mg/kg) was used at the lowest dosage
to induce general anesthesia, minimizing effects on seizure

BIOL PSYCHIATRY
2000;48:222–228

223

threshold. Succinylcholine (0.5–1 mg/kg) served as the muscle
relaxant. Atropine (0.4 mg intravenously) was administered
approximately 2 min before the anesthetic. Patients were oxygenated from anesthetic administration until postictal resumption
of spontaneous respiration. Bitemporal bilateral electrode placement was used throughout. The tourniquet method and two
channels of prefrontal electroencephalogram (EEG) were used to
assess seizure duration. An adequate seizure was defined as a
tonic-clonic motor convulsion occurring bilaterally for at least 30
sec, plus EEG evidence of a cerebral seizure. Reliance on the
duration of motor manifestations to define adequacy was conservative because EEG ictal expression typically outlasts motor
expression for several seconds (Sackeim et al 1991; Warmflash
et al 1987). Grossly suprathreshold stimulation can result in
reduced seizure duration, below conventional cutoffs for “adequacy” (American Psychiatric Association Task Force, in press;
Sackeim et al 1991); however, it was felt that the stimulus
intensities used here, all adjusted relative to initial seizure
threshold, would be insufficient to result in a marked shortening
of seizure duration. In each treatment one adequate seizure was
elicited.
Using the empirical titration technique (Sackeim et al 1987c),

seizure threshold was quantified at the first two treatment
sessions and was defined as the minimal electrical stimulus (in
millicoulombs) to produce a motor seizure duration of at least 30
sec. For the MECTA SR 1, the titration schedule followed that
used by Coffey et al (1995). With the Thymatron DGx, the first
stimulus at the first treatment session was 10% of total charge. If
this failed to produce an adequate seizure, electrical dosage was
increased in 10% steps. This approach roughly matched the
charge delivered by the MECTA SR 1 and Thymatron DGx at
each step in the titration schedule. There was a limit of four
stimulations in a session, but the maximal number administered
in this sample was three. A 40-sec interval elapsed between each
step in the titration, and no patient required additional thiopental.
At the second treatment session, patients were stimulated with
an intensity 5% below the first treatment’s threshold value. If this
failed to produce an adequate seizure, the first session’s value
was adopted as the initial seizure threshold (ST). Patients were
then stimulated with the assigned electrical stimulus charge
(either 1, or 2, or 4 3 ST). If the decreased intensity produced an
adequate seizure, this new value was taken as the ST, and there

was no further stimulation in that session. At subsequent sessions
in the 1 ST group, if needed, electrical stimulus dosage was
increased by one step to achieve an adequate seizure. In the 2 ST
and 4 ST groups, the duration of motor seizures was ignored
during the three subsequent sessions. Afterward, if the seizure
was shorter than 30 sec, the delivered charge was increased by
one step. At the 10th treatment session, all patients were
reassessed for ST. The stimulus charge was then adjusted based
on the assigned ST group or to the maximal charge settings of the
device.

Clinical Evaluation
The criterion for clinical response corresponded to a BPRS score
of 25 or less, as described elsewhere (Chanpattana 1997). The
patients who manifested this level of clinical improvement went

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W. Chanpattana et al

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2000;48:222–228

Table 1. Demographic and Clinical Features of the Sample
Treatment groupa
Variable
Age
Gender
Education (years)
Subtypeb
Onset of illness (years)
Duration of illness (years)
Episode duration (years)
Number of prior psychiatric admissions
Prior failure of adequate NT trials
Duration of NT trials (months)
Mean CPZ equivalent dose (mg)
Prior failure of flupenthixol
Family history of schizophrenia
BPRS at entry

MMSE at entry
GAF at entry
Dosage of flupenthixol (mg)
Seizure threshold (mC)
Baseline
Tenth
Increment

1 ST (n 5 21)

2 ST (n 5 21)

4 ST (n 5 20)

35.1 6 8.3 (21– 48)
9 men, 12 women
9.8 6 12.9 (4 –16)
13 P, 6 D, 2 U
19.5 6 4.6 (12–32)
15.7 6 7.9 (3–32)
3.6 6 3.5 (1 month–12 years)
7.5 6 4.0 (2–15)
3.5 6 1.1 (2– 6)
24.8 6 27.5 (2.4 –126)
1191.2 6 263.2 (825–1,900)
5 patients
3 patients
51.8 6 10.7 (39 –73)
24.0 6 5.6 (14 –30)
29.2 6 7.4 (20 – 45)
22.9 6 2.4 (18 –24)

35.2 6 8.2 (21– 49)
10 men, 11 women
8.0 6 3.6 (4 –15)
12 P, 5 D, 1 C
21.2 6 5.6 (15–35)
14.0 6 7.3 (3–32)
3.1 6 3.3 (2 months–12 years)
6.2 6 5.8 (1–26)
3.4 6 1.0 (2– 6)
20.0 6 16.6 (3–72)
1283.7 6 358.1 (833–2,080)
6 patients
2 patients
48.7 6 7.2 (37– 67)
21.5 6 5.3 (14 –30)
26.8 6 4.1 (22–36)
23.1 6 2.2 (18 –24)

33.5 6 7.4 (20 – 48)
8 men, 12 women
8.5 6 3.2 (4 –16)
15 P, 4 D, 1 U
20.7 6 5.6 (14 –35)
12.9 6 5.5 (3–25)
3.2 6 3.2 (3 months–10 years)
7.4 6 5.4 (2–22)
3.4 6 1.4 (2–7)
18.2 6 16.8 (2.5–72)
1256.7 6 288 (800 –1,775)
6 patients
4 patients
47.9 6 6.1 (38 – 60)
23.2 6 4.3 (13–30)
27.6 6 4.7 (22–36)
23.1 6 2.2 (18 –24)

75.4 6 30.0 (48 –128)
184.3 6 95.2 (48 – 403)
107.5 6 84.8 (0 –323)

79.5 6 23.4 (48 –128)
188.9 6 105.5 (75.6 – 460.8)
108.8 6 111.0 (0 – 412.8)

81.2 6 28.7 (48 –128)
229.5 6 75.3 (128 – 403)
147.8 6 86.0 (48 –355.2)

a

Treatment groups: 1 ST, dose just above seizure threshold (ST); 2 ST, 2 3 ST; 4 ST, 4 3 ST.
Subtype: P, paranoid; D, disorganized; C, catatonia; U, undifferentiated.
Values are mean 6 SD (range). NT, neuroleptic; CPZ, chlorpromazine, BPRS, Brief Psychiatric Rating Scale; MMSE, Mini-Mental State Exam; GAF, Global
Assessment Functioning; mC, millicoulombs.
b

on to a 3-week stabilization period (Chanpattana 1998, 1999;
Chanpattana et al 1999a, 1999b). The stabilization period comprised the following treatment schedule: 3 ECT treatments in the
first week, then once a week for the second and third weeks
(during which BPRS scores of 25 or less had to be consistently
maintained). If BPRS scores rose above 25 at any time during
this period, and the total number of ECT treatments was less than
20, patients returned to the acute ECT treatment regimen and
repeated the acute phase and stabilization schedules again.
Patients with BPRS scores above 25, who had already received
20 ECT treatments, were considered ECT nonresponders. The
same considerations applied to the patients who had not shown
significant improvement (BPRS . 25) until their 20th ECT
treatment. Thus, ECT responders were patients who completed
the 3-week stabilization period during which the BPRS score
assessed before each treatment was consistently 25 or less.
Measures used to assess study outcome were 1) BPRS assessed before each treatment, during the acute and stabilization
periods, and end of the study (1 week after the last treatment); 2)
Global Assessment of Functioning (GAF) assessed before each
acute treatment and at the end of the study; and 3) the MiniMental State Exam (MMSE, Thai version; Kongsakon and
Vanichtanom 1994) assessed at the same time as the BPRS.
Three psychiatric nurses served as raters, masked to the treatment
conditions. Each patient was rated by the same nurse. These
raters underwent training for 12–24 months. Interrater reliability
was assessed. Each rater provided ratings simultaneously on 10
patients. Each patient was interviewed by a psychiatrist for 20
min. The correlations of BPRS scores between each rater and the
psychiatrist indicated strong reliability (0.93, 0.96, and 0.97).

Statistical Analyses
The results are expressed as mean 6 SD. Seizure threshold data
were analyzed after logarithmic transformation to improve the
normality of the data distribution (Sackeim et al 1987b). For
discontinuous data, chi-square tests were used to test for differences among the groups. One-way analyses of variance
(ANOVA) were used to compare the three treatment groups in
continuous demographic and clinical variables. Significant main
effects of treatment group were followed by Scheffe´ post hoc
comparisons to identify pair-wise differences. The groups were
compared in speed of response by conducting ANOVAs on the
number of ECT treatments and the number of days in ECT
treatment for patients who met initial and final remitter criteria.
In addition, across the total sample, Kaplan-Meier survival
analyses were conducted on these measures, treating ECT
nonresponders as censored observations.

Results
Sixty-seven patients with schizophrenia received ECT.
Five patients dropped out, leaving 62 patients in the study.
All 5 patients who dropped out withdrew consent, reporting fear of ECT, despite receiving basic information about
ECT and schizophrenia. Table 1 presents demographic and
clinical features of the 62 patients as a function of
treatment condition. There were no significant differences
among the three treatment groups in any variable.
Thirty-three patients maintained remitter status through

ECT Stimulus Intensity

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2000;48:222–228

225

Table 2. Treatment Features of Electroconvulsive Therapy (ECT) Remitters
Treatment Groupa
Variable
Seizure threshold (mC)
First
Tenth
Average charge (mC per session)
Sessions 2–9
Sessions 11– end
At first improvement
No. of ECT treatments
Days of treatment
At the end of study
No. of ECT treatments
Days of treatments

1 ST (n 5 11)

2 ST (n 5 11)

4 ST (n 5 11)

68.4 6 16.1 (48 – 80)
179.5 6 97.3 (80 – 403)

83.2 6 23.3 (48 –128)
222.5 6 93.8 (126 – 403)

77.3 6 29.1 (48 –128)
224 6 55.4 (192–288)

118.4 6 47.1 (68 –196)
254.6 6 131 (128 –533)

195.6 6 32.9 (151–259)
413.1 6 139 (230 –576)

372.2 6 66.5 (245– 461)
576 all

13.6 6 5.0 (4 –18)
35.4 6 16.3 (7–58)

7.5 6 3.8 (3–15)
16.4 6 11.9 (4 – 42)

4.2 6 1.5 (3–7)
7.0 6 3.6 (4 –14)

18.6 6 5.0 (9 –23)
56.4 6 16.3 (28 –79)

12.5 6 3.8 (8 –20)
37.5 6 12.0 (25– 63)

9.2 6 1.5 (8 –12)
28.0 6 3.6 (25–35)

Valus are given in mean 6 SD (range). mC, millicoulombs.
a
Treatment groups: 1 ST, dose just above seizure threshold (ST); 2 ST, 2 3 ST;4 ST, 4 3 ST.

the stabilization period and were classified as ECT responders. There was no difference in response rate among
the three treatment groups [52%, 52%, and 55% for 1 ST,
2 ST, and 4 ST, respectively; x2(2) 5 0.04, ns]. There
were 11 patients in each treatment group. The three
treatment groups did not differ in any of the demographic
or clinical variables listed in Table 1.
Table 2 presents the treatment features for the remitted
patients as a function of the ECT conditions. Compared
with remitters in the low-dosage group, remitters in both
the 2 ST and 4 ST groups received fewer ECT treatments
at the time of first significant clinical improvement,
defined as a BPRS score of 25 or less [F(2,30) 5 18.70,
p , .0001; 1 ST vs. 2 ST, p 5 .002; 1 ST vs. 4 ST, p ,
.0001] and had fewer days in ECT treatment [F(2,30) 5
16.35, p , .0001; 1 ST vs. 2 ST, p 5 .003; 1 ST vs. 4 ST,
p , .0001]. The 2 ST and 4 ST groups did not differ
significantly in these measures (Table 2), although the
pattern of means suggested more rapid onset of improvement in the 4 ST relative to the 2 ST group (p 5 .19).
At the end of study, the same effects were manifest.
Remitters in both the 2 ST and 4 ST groups received fewer
treatments [F(2,30) 5 18.70, p , .0001; 1 ST vs. 2 ST,
p , .002; 1 ST vs. 4 ST, p , .0001] and had fewer days
in treatment than remitters in the low-dosage group
[F(2,30) 5 16.29, p , .0001; 1 ST vs. 2 ST, p 5 .003; 1
ST vs. 4 ST, p , .0001]. The 2 ST and 4 ST groups did not
differ in these measures (Table 2), although again the 4 ST
group averaged three fewer treatments than did the 2 ST
group (p 5 .13). Including the stabilization phase, remitters in the 1 ST group on average received 18.64 (SD 5
4.95) treatments, whereas the 2 ST remitters averaged
12.46 (SD 5 3.75) treatments and the 4 ST remitters
averaged 9.18 (SD 5 1.47) treatments.
These effects were reexamined using survival analysis
on the total sample of 62 patients, with ECT nonre-

sponders treated as censored observations. The survival
analysis on number of ECT treatments administered
yielded a significant effect of treatment group [Figure 1;
log-rank x2(2) 5 25.00, p , .0001], as did the analysis of
the number of days in treatment [log-rank x2(2) 5 24.38,
p , .0001].
The extent of clinical improvement was comparable
among the three remitter groups. At the end of the study,
the 1 ST, 2 ST, and 4 ST remitter groups, respectively, had
62.6%, 60.8%, and 65.6% reductions in BPRS scores and
55.5%, 66.7%, and 55.8% increases in GAF scores. In the
total sample, ANOVAs were conducted on the percentage
change from baseline to study exit in BPRS, GAF, and
MMSE scores, with treatment group and remitter status as

Figure 1. Kaplan–Meier survival plot for cumulative probability
of nonresponse as a function of the number of electroconvulsive
therapy (ECT) treatments. Groups were treated just above seizure
threshold (1 3 ST), two times above threshold (2 3 ST), or four
times above threshold (4 3 ST).

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BIOL PSYCHIATRY
2000;48:222–228

between-subject factors. In the ANOVA on change in
BPRS scores there was only a main effect of remitter
status [F(1,56) 5 102.37, p , .0001]. Similarly, there was
only a main effect of remitter status in the ANOVA on
change in GAF scores [F(1,56) 5 18.23, p , .0001]. This
indicated that the treatment groups were equivalent in the
degree of change in symptoms and functional status. The
ANOVA on MMSE scores produced no significant effects, indicating that change in global cognitive status was
independent of treatment condition and remitter status.
In the total sample, the three treatment groups did not
differ in initial seizure threshold [F(2,59) 5 0.40, p 5 .67]
or in the percentage increase in threshold from the first to
tenth treatment [F(2,47) 5 0.79, p 5 .46; Table 1].
Patients who did or did not achieve remitter status did not
differ in initial seizure threshold [t(60) 5 0.45, p 5 .65] or
in the increase in threshold [t(48) 5 0.41, p 5 .68].
Although there is some evidence that response to ECT in
major depression is associated with a larger cumulative
seizure threshold increase (Sackeim 1999; Sackeim et al
1987b), this does not appear to be the case in
schizophrenia.

Discussion
This study found that speed of clinical response to bilateral
ECT in patients with schizophrenia is influenced by the
degree to which stimulus dosage exceeds seizure threshold. Both of the high-dosage groups had more rapid
improvement than did the low-dosage group. The findings
parallel the results reported in patients with major depression ( Nobler et al 1997; Ottosson 1960; Robin and De
Tissera 1982; Sackeim et al 1993, in press). This is of
clinical importance because ECT is frequently used when
rapid improvement is needed. This was the first ECT study
examining the effect of stimulus intensity in patients with
schizophrenia.
Dosage factors, which are known to have greater impact
on the efficacy of right unilateral ECT, may also influence
the therapeutic properties of bilateral ECT. In major
depression, Ottosson (1960) examined the effects of stimulus dose intensity on the efficacy of bilateral ECT.
Although there was no effect of dosage on response rate,
speed of symptom reduction was faster in patients who
received a stimulus intensity that was markedly suprathreshold. Cronholm and Ottosson (1963) reported that
low-intensity, ultra-brief pulse, bilateral ECT was less
effective than higher intensity, sinusoidal waveform, bilateral ECT. Robin and De Tissera (1982) found that with
bilateral ECT, high-intensity brief-pulse or chopped sine
wave stimulation resulting in faster clinical improvement
than did low-intensity brief-pulse stimulation. Sackeim et
al (1993) randomly assigned patients to four treatment

W. Chanpattana et al

conditions: low-dosage right unilateral ECT, high-dosage
right unilateral ECT, low-dosage bilateral ECT, and highdosage bilateral ECT. They found that regardless of
electrode placement, the high-dosage groups had more
rapid improvement than did the low-dosage groups. In
addition, low-dosage right unilateral ECT had poor efficacy. In another four-group study, Sackeim et al (in press)
found that markedly suprathreshold (6 3 ST) right unilateral ECT and moderate dosage (2.5 3 ST) bilateral ECT
were more effective and resulted in more rapid improvement than lower intensity (1.5 3 ST and 2.5 3 ST) right
unilateral ECT. Thus, in studies of major depression, there
have been repeated findings that stimulus intensity impacts on speed of clinical response. This study extends this
observation to patients with schizophrenia.
Analyses restricted to the remitter sample and survival
analyses of the total sample both supported the conclusion
that higher stimulus intensity resulted in more rapid
improvement in patients with schizophrenia. The analyses
in the remitter sample were particularly critical because
comparisons of speed of clinical improvement are most
relevant when restricted to patients who actually respond
(Laska and Siegel 1995; Nobler et al 1997). This approach
also avoids confounding likelihood of response (efficacy)
with speed of response (efficiency). There was no evidence in this study that the stimulus-intensity conditions
differed in likelihood of response or degree of symptomatic improvement.
An unusual aspect of this study was the use of a 3-week
stabilization period as a screening method to identify
remitters (Chanpattana 1998, 1999; Chanpattana et al
1999a, 1999b). The stabilization period started immediately after the first sign of significant clinical improvement
(BPRS # 25). Stability of clinical symptoms across these
3 weeks was required for classification as an ECT remitter.
Therefore, ECT remitters in this study maintained clinical
improvement for a substantial period of time.
This preliminary study had a number of limitations. A
washout period for previous antipsychotic medications
was not used because all study patients were in psychotic
exacerbations, and many patients were difficult to manage.
Lack of a washout may have had a substantial effect on the
patient’s initial seizure threshold because many patients
had prior treatment with low potency neuroleptics (Sackeim et al 1991). In contrast, all patients were treated with
flupenthixol, a typical neuroleptic with a potency about
1.5 times that of haloperidol. A fixed titration schedule of
flupenthixol dosage was used to minimize variability in
effects on seizure threshold.
A structured diagnostic instrument was not used. Instead, the diagnosis of schizophrenia was based on the
consensus of at least three psychiatrists, which had to
concur with the patients’ psychiatric records throughout

ECT Stimulus Intensity

the episode of illness. Theoretically, the inclusion in the
sample of patients with depressive or manic disorders
could account for the concordance of the results with
similar studies major depression. The relatively high
representation of female patients might suggest this possibility. That the patients presented with schizophrenia is
supported by the average episode duration of approximately 3.5 years (Table 1) and relatively low baseline
scores on the BPRS items of depressive mood, grandiosity, and excitement, coupled with high scores on traditional BPRS positive symptoms of psychosis (data not
shown).
It is well documented that ECT produces cognitive
impairment (American Psychiatric Association Task
Force, in press; Sackeim 1992). There were no differences
among the treatment groups or among ECT responders
and nonresponders in change in MMSE scores. Although
this suggests that the dosage conditions did not differ in
changes in global cognitive status, the MMSE is a measure
insensitive to the characteristic effects of ECT on anterograde and retrograde memory (Sobin et al 1995). In major
depression, there is evidence that higher stimulus intensity
and longer courses of ECT treatment can result in more
severe transient cognitive side effects (Sackeim 1992;
Sackeim et al 1993). It will be important in future research
to use more sensitive neuropsychologic measures and
determine in patients with schizophrenia whether the
enhancement in speed of response due to higher stimulus
intensity offsets a detrimental effect of cognitive function.
In summary, this preliminary study indicates that in
patients with schizophrenia, electrical dosage impacts on
the speed of clinical response to bilateral ECT. Both the
groups treated at twice and four times seizure threshold
had more rapid improvement than did the low-dosage
group, who were treated just above seizure threshold.
Future research should examine the effects of high-dosage
bilateral ECT on cognitive functions, which should be
assessed with a comprehensive neuropsychological
battery.

Supported in part by Grant No. BRG 3980009 from the Thailand
Research Fund (WC) and Grant No. R37 MH35636 from the National
Institute of Mental Health (HAS). The authors thank Wiwat Yatapootanon, M.D., for technical support and the nursing staff of the Srithunya
mental hospital.

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