The present study aimed to report the initial seizure threshold (IST) of a brief-pulse bilateral electroconvulsive therapy (BP-BL ECT) in Korean patients with schizophrenia/schizoaffective disorder and to identify IST predictors.
Among 67 patients who received ECT and diagnosed with schizophrenia/schizoaffective disorder based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, we included 56 patients who received 1-millisecond BP-BL ECT after anesthesia with sodium thiopental between March 2012 and June 2018. Demographic and clinical information was gathered from electronic medical records, and a multiple regression analysis was conducted to identify predictors of the IST.
The mean age of the patients was 36.9±12.0 years and 30 (53.6%) patients were male. The mean and median IST were 105.9±54.5 and 96 millicoulombs (mC), respectively. The IST was predicted by age, gender, and dose (mg/kg) of sodium thiopental. Other physical and clinical variables were not associated with the IST.
The present study demonstrated that the IST of 1-ms BP-BL ECT following sodium thiopental anesthesia in Korean patients was comparable to those reported in previous literature. The IST was associated with age, gender, and dose of sodium thiopental.
Electroconvulsive therapy (ECT) is a safe and effective treatment for various psychiatric disorders and conditions [
However, IST determination is not a straightforward task, as it varies up to 40 times for different individuals [
Several methods of IST determination have been proposed, including age-based, half-age-based, fixed-high, and empirical titration methods [
The influence of race and ethnicity on IST is not yet clear [
The present retrospective study based on chart-review aimed to report the distribution of IST values in Korean patients following a specific protocol. Especially, this study had focused on patients diagnosed with either schizophrenia or schizoaffective disorder. To date, studies on IST done with psychotic patients were hard to find [
Patients who underwent an acute course of ECT under the diagnosis of schizophrenia or schizoaffective disorder from March 2012 to June 2018 at the ECT center of Dongguk University International Hospital were identified as eligible subjects. Diagnoses were confirmed by the physician-in-charge and one of the authors (CIW) after the chart review in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR).
In an effort to report the IST distribution following a specific protocol, only the patients who had received 1-ms BP-BL ECT after anesthesia with sodium thiopental were selected, which constituted the majority of the all eligible subjects. Information on demographic characteristics, clinical characteristics, ECT history, and use of concomitant medications (antipsychotics, anticonvulsants, antidepressants, and benzodiazepines) was obtained from electronic medical records (EMR). The study proposal was approved by the Institutional Review Board of Dongguk University International Hospital (2018-10-003).
The ECT session was commenced only after completion of psychiatric and medical work-ups. The administration of anticonvulsants and/or benzodiazepines was stopped or reduced the day before the ECT session in all patients. The MECTA spECTrum 5,000Q (MECTA Corp; Lake Oswego, OR, USA) was used to deliver the electrical stimulus, and BP-BL ECT was the primary recommendation if there were no concerns about memory or cognitive impairments. The seizure was monitored in three ways: electroencephalography (EEG), electrocardiography (ECG), and motor movement measuring by an optical motion sensor (OMS) under the tourniquet method. The anesthesia and muscle relaxation procedures were described in detail in a previous report issued by our research group [
The IST was measured at the first ECT session by empirical titration method. The stimulus intensity was increased according to a predetermined schedule (
The demographic and clinical characteristics of the patients are presented in
In total, 67 patients with schizophrenia or schizoaffective disorder received ECT during the study period. Among them, 56 (83.5%) had undergone a 1-ms BP-BL ECT after anesthesia with sodium thiopental. These patients were included in the present analysis. The excluded patients were 1) seven patients with the right unilateral electrode placement and 2) four patients with propofol-induced anesthesia.
The mean age of the study subjects was 36.9±12.0 years, and 30 patients (53.6%) were male. There were no gender differences in educational level, occupation, family history, intelligence quotient (IQ) proportion and duration of illness, but the mean BMI of the male subjects (27.1±5.4) was significantly higher than that of the female subjects (24.0±5.3; t=2.158, p=0.035). The medication-related variables, such as chlorpromazine-equivalent dose, use of clozapine, and use of concomitant anticonvulsants, antidepressants, or benzodiazepines, did not differ between the male and female subjects (
The mean IST of the study subjects was 105.9±54.5 millicoulomb (mC; range: 48–288 mC) (
A multiple regression analysis with stepwise variable selection procedure suggested that age, gender and the dose per body weight (mg/kg) of sodium thiopental were the most relevant and parsimonious set of predictors (
The relationship between IST and the set of relevant predictors (age, gender, and a dose of sodium thiopental) is depicted in
Other clinical variables related to the use of concurrent medications (clozapine, anticonvulsants, antidepressants, and benzodiazepines) were not significantly related to IST. Neither were they included in the final model nor any of the t-test for each variable revealed group difference.
This study explored the overall IST distribution in Korean patients with schizophrenia and schizoaffective disorder. The mean and median values of IST were 105.9 mC and 96 mC respectively. The distribution was highly right-skewed with about 80% of the study subjects below the IST value of 128 mC. The range was 48–288 mC and the variability was a six-fold difference. The obtained IST was much higher than those reported from unilateral electrode placement [
The largest studies so far which have explored IST values in representative samples of patients were done by Nitturkar et al. [
This comparison gives the impression that the IST values from Korean subjects are rather low than from the American or Indian population. However, IST values reported in other small or medium-sized studies were in the lower or similar range as the present study irrespective of race or ethnicity (
This study replicated the well-known fact that IST values are significantly associated with age and gender. Older age and being male predict a higher IST [
Apart from this, another finding was the association between thiopental dose and IST. Traditionally, methohexital, etomidate, thiopental, and propofol have been used in ECT and there is no robust evidence to recommend a particular agent [
In an ECT center, an operation protocol is usually predefined according to the characteristics of the patient population and the ECT equipment. It dictates the employed ECT method, stimulus dose titration method, anesthesia-related procedures and policy on concomitant medication. In this case, estimating the IST distribution and finding the possible predictors of IST on that protocol would be important in several aspects. The Royal College of Psychiatrists recommends that the selection of the electrical dose should be individualized and contingent upon the IST value determined in the first session [
Thus, the balance between harm and benefit of the empirical titration partly depends on the location and range of the expected IST value distribution. Past authors have had very different views on the extent of the IST variability. Some authors reported as high as 40-fold variation [
The present study described an IST reference in Korean patients following a certain predefined protocol as an example. In order to successfully manage and to set up a procedure protocol of ECT, a preliminary determination of IST values stratified by sex, age and other variables may have to be defined based on past experience and accumulated data. In this case, the reference data described in the present study could be helpful in deciding whether the obtained IST values were within a comparable range and whether the similar variables could partly predict the individual IST values. Admittedly, the number of subjects in the present study was only modest for obtaining adequate generalizability and for properly investigating the determinants of IST with all their interactions. This may limit the value of the present findings. Undoubtedly, a universal reference which can be applied to every case is fundamentally unobtainable since every ECT center would deal with different patient populations and employ different ECT procedures. Minor changes in the implemented protocol may influence the overall distribution. Therefore, the data in the present study could only be used as a starting point to define each center’s own reference guide suited to its own needs
In conclusion, the present study reported an IST value distribution in Korean patients and replicated the previous finding that age and gender were independent predictors of IST. Additionally, it demonstrated that the dose of sodium thiopental per body weight was another predictor of IST. The described IST distribution was comparable to previous studies and the empirical titration method seemed appropriate to deal with most of the cases. Taken together, these findings may be used as a reference for estimating the IST in patients with schizophrenia or schizoaffective disorder. However, it has to be mentioned that this result only applies to Korean patients who underwent 1-ms BP-BL ECT following sodium thiopental anesthesia. It may limit the generalizability of the study result.
This study was supported by research grants of Clinical Institute of Psychopharmacology, Dongguk University Medical Center and Whanin Pharm. Co. LTD.
Dr. Kim YS received grants, research support and honoraria from Janssen, Otsuka, and Dainippon Sumitomo. Dr. Chung IW received research and educational grants from Janssen, Otsuka, Hanmi, Mecta, and Whanin. Dr. Youn T received research and educational grants from Otsuka, Eisai, Hanmi, Lundbeck, and Mecta. The others have nothing to declare.
Conceptualization: Yong Sik Kim, In Won Chung. Data curation: Young Wook Jeong, Jin Hyeok Jang. Formal analysis: Seong Hoon Jeong, Tak Youn. Funding acquisition: Yong Sik Kim, In Won Chung. Investigation: Yong Sik Kim, In Won Chung, Young Wook Jeong. Methodology: In Won Chung, Jin Hyeok Jang, Tak Youn. Project administration: In Won Chung, Tak Youn. Resources: In Won Chung, Yong Sik Kim. Software: Seong Hoon Jeong, Younsuk Lee, Jin Hyeok Jang. Supervision: Yong Sik Kim, Younsuk Lee. Validation: Seong Hoon Jeong, Younsuk Lee, Tak Youn. Visualization: Seong Hoon Jeong, In Won Chung. Writing—original draft: Seong Hoon Jeong, In Won Chung. Writing—review & editing: Yong Sik Kim, Seong Hoon Jeong.
The distibution of IST after 1-millisecond pulse width BP-BL ECT. The IST values were estimated by empirical titration methods according to a predefined protocol. The subjects were 56 patients with schizophrenia and schizophreniform disorder. ECT was administered after anesthesia with sodium thiopental (gray dots are the actual cases and the thick black line is the estimated kernel density). IST: initial seizure threshold, BP-BL: brief-pulse bilateral, ECT: electrovulsive therapy.
Relationships between IST and age, gender, and dose of sodium thiopental in patients who underwent BP-BL ECT after anesthesia with sodium thiopental. The overlaid lines represent the linear regression lines through respective subsets of study subjects. A: Relationship between IST and age stratified by gender and dose (mg/kg) of sodium thiopental using an arbitrary categorization of dose into three non-overlapping ranges with equal numbers of patients. B: Relationship between IST and dose (mg/kg) of sodium thiopental stratified by gender and age using an arbitrary categorization of age into three non-overlapping ranges with equal numbers of patients. IST: initial seizure threshold, BP-BL: brief-pulse bilateral, ECT: electrovulsive therapy.
Summary of demographic, ECT, medication related variables and the estimated IST of the study subjects who underwent BP-BL ECT after anesthesia with sodium thiopental (N=56)
Variables | Total (N=56) | Male (N=30) | Female (N=26) | Male vs. female p-values |
---|---|---|---|---|
Demographic variables | ||||
Age (years) | 36.9±12.0 |
33.4±11.5 | 40.9±11.5 | 0.018 |
Weight (kg) | 70.6±18.1 | 79.7±16.0 | 60.2±14.5 | <0.001 |
Height (cm) | 165.5±8.5 | 171.6±4.9 | 158.4±5.8 | <0.001 |
BMI (kg/m2) | 25.6±5.5 | 27.1±5.4 | 24.0±5.3 | 0.035 |
Duration of illness (years) | 12.2±7.8 | 12.5±7.9 | 11.8±7.8 | 0.729 |
ECT variables | ||||
Thiopental dose (mg) | 214.7±62.5 | 240.8±59.3 | 184.6±52.5 | <0.001 |
Thiopental dose/weight (mg/kg) | 3.1±0.6 | 3.0±0.5 | 3.1±0.7 | 0.725 |
IST (millicoulomb) | 105.9±54.5 | 115.2±59.9 | 95.2±46.3 | 0.174 |
Concomitant medications | ||||
Chlorpromazine-equivalent dose of antipsychotics (mg) | 667.2±458.6 | 695.6±430.8 | 634.4±495.3 | 0.623 |
Clozapine use (yes/no) | 40/16 | 20/10 | 20/6 | 0.102 |
Anticonvulsant use (yes/no) | 27/29 | 16/14 | 11/15 | 0.579 |
Antidepressant use (yes/no) | 14/42 | 8/22 | 6/20 | 1.000 |
Benzodiazepine use (yes/no) | 39/17 | 16/10 | 23/7 | 0.349 |
numbers are expressed as mean±standard deviation or as the frequency of yes/no. The difference between male and female subjects was statistically tested with Student t-tests for continuous variables and chi-square test for dichotomous variables.
ECT: electroconvulsive therapy, IST: initial seizure threshold, BP-BL: Brief-pulse Bilateral, BMI: body mass index
The final output of multiple regression analysis with IST as the dependent variable after the stepwise variable selection procedure
Predictors |
β estimate | Standardized β | Standard error | t-value | p-value |
---|---|---|---|---|---|
Age | 1.63 | 0.354 | 0.59 | 2.76 | 0.008 |
Gender | -33.65 | -0.337 | 14.03 | -2.40 | 0.020 |
Thiopental dose per weight (mg/kg) | 27.35 | 0.291 | 11.53 | 2.37 | 0.021 |
Overall F-statistic: 4.81 (3,52) | p=0.005 | R2=0.217 | Adjusted R2=0.172 |
these predictors were selected as the most parsimonious set of influential predictors for predicting IST. The most optimal model was chosen based on AIC. All predictors contained in the model significantly predicted IST values at p-values <0.05. The model explained 21.7% of the total variance.
IST: initial seizure threshold, AIC: Akaike’s Information Criteria
Previous studies of the IST distributions in bilateral electroconvulsive therapy
Study | IST (Mean±SD) | Median | Range | Diagnosis | Anesthetics | Ethnicity | Number of participants |
---|---|---|---|---|---|---|---|
Coffey et al. [ |
86.4±34.9 | Affective disorder | Methohexital | American | 25 | ||
Scott et al. [ |
75 | 50–200 | Depressive disorder | Methohexitone | European | 100 | |
Chanpattana et al. [ |
91.3±31.2 | Schizophrenia | Thiopental | Asian (Thai) | 93 | ||
Chung and Wong [ |
117.4±65.6 | 48–403 | Mixed | Thiopentone | Asian (Chinese) | 54 | |
Chung and Wong [ |
105.5±40.6 | 48–192 | Mixed thiopentone | Asian (Chinese) | 22 | ||
Chung [ |
115.1 | 48–403 | Mixed | Thiopentone | Asian (Chinese) | 105 | |
Petrides et al. [ |
126.0±69.7 | 100 | 25–400 | Depressive disorder | Methohexital | American | 402 |
van Waarde et al. [ |
111.6 | Mixed | Mixed | Meta-analysis | 1,116 | ||
Bennett et al. [ |
125 | 50–300 | Depressive disorder | (Not informed) | European | 62 | |
van Waarde et al. [ |
95.4±59.5 | Depressive disorder | Etomidate | European | 28 | ||
Yashuda et al. [ |
136 | 50.4–403 | Major depressive disorder | Thiamylal | Asian (Japanese) | 54 | |
Nitturkar et al. [ |
130.4±52.0 | Mixed | Thiopentone | Asian (Indian) | 640 | ||
Chi et al. [ |
186.7±35.1 | Mixed | Propofol | Asian (Korean) | 43 | ||
Present study | 105.9±54.5 | 96 | 48–288 | Schizophrenia | Thiopental | Asian (Korean) | 56 |
SD: standard deviation, IST: initial seizure threshold