Efficacy and safety of modified electroconvulsive therapy for the refractory depression in older patients

We explored the clinical efficacy and safety of modified electroconvulsive therapy (ECT) in the treatment of elderly patients with refractory depression.

risk (Zhou, Z, & Xie, 2012). It has become a difficult psychiatric problem at present, and there is no feasible way to cure it. Studies have shown that the response rate of modified electroconvulsive therapy (ECT) can achieve 80% to 90% in the acute stage of the elderly patients with geriatric depression, and the rate of its safety is also relatively high (Zhao, Fan, Dong, & Meng, 2015). ECT is a method to treat psychosis by giving a certain amount of electric current to stimulate the brain after intravenous injection of anesthetics and muscle relaxants, so as to induce epileptic discharge in the cerebral cortex. Compared with the traditional electroshock, this method has higher safety, wider application, and less adverse reactions. However, there are few reports on the remission rate of ECT in elderly patients with refractory depression. Our study aimed to explore the efficacy and safety of ECT in the treatment of older patients with refractory depression. Inclusion criteria: (1) meet the diagnostic criteria of depression(international classification of Diseases 10th Edition); (2) age ≥ 60 years old; (3) according to their history of diseases, the treatments over 3 months with two or more antidepressants with different chemical structures in sufficient quantity are ineffective; furthermore, for patients with primary (first-attack) depression, the treatments over 6 months with two antidepressants with different chemical structures in sufficient quantity are ineffective; (4) primary school education or above; (5) patients and guardians fully understand the process and voluntarily signed informed consents.

| Clinical data
A total of 46 patients were enrolled in our study, 3 patients failed to complete the treatment due to discharge, and 43 patients (18 male and 25 female) completed the tests and their results were analyzed subsequently. Among them, the age ranged 60 to 75 years old, the average age was 65 ± 4.8 years old, and the average course of the disease was 7.5 ± 5.1 years. In addition, the initial average score of HAMD was 35.89 ± 6.84, and it was calculated as 22.16 ± 6.56 in terms of HAMA. Three patients met the inclusion criteria but were not included in this study. One patient only completed three treatments, and after the symptoms were partially relieved, the patient's family asked to be discharged. One patient was discharged without electroconvulsive therapy for personal reasons. One patient was discharged in advance because of medical insurance problems and did not receive treatment.

| ECT
Physical examinations were carried out before the procedure, including routine blood examination, urine routine, liver and kidney function, blood glucose, myocardial enzyme spectrum, electrocardiogram, chest film, and head CT. For patients accompanied by hypertension, coronary disease, and diabetes, the following related indexes should be controlled before the operation: (1) blood pressure was controlled to less than 140/less than 90 mmHg; (2) myocardial enzyme spectrum and cardiac troponin were in the normal range; (3) the value of fasting blood glucose was controlled to less than 8.0 mmol/L, and (4) urine glucose was detected to be negative.
Before ECT, etomidate (0.15 mg/kg) and propofol (1 mg/kg) were administered by intravenous bolus after an intravenous bolus of atropine (0.5 mg). After the disappearance of the ciliary reflex and fixation of the eyeball, 0.2% succinylcholine chloride (1 mg/kg) was administered by intravenous bolus injection, then ECT could be carried out.
Electrodes were placed on the bilateral temporal side of the patients, and multifunctional electrospasmodic therapeutic apparatus (type IV) (Somatics, US) was used for ECT in this study. Based on the age and weight, the pulse electric stimulation therapy was carried out according to the energy percentage. The heart rate, blood pressure, respiration, blood oxygen saturation (SpO 2 ), and electrocardiogram (ECG) were monitored dynamically during the treatment. After the operation, ECG monitoring was carried out for 2 hours, as well as vital signs and SpO 2 were monitored continuously.
ECT treatment was taken once every other day, three times a week, and 8 to 12 times in total for each patient. If patients received an administration of benzodiazepines, they should be stopped once before each ECT, and the dosages of antidepressants used before and after operation remained constant despite the application of ECT.
The stimulation energy of ECT was determined by energy preconception, and the value of the first energy was calculated as age × 50%. Then, the stimulation energy was adjusted based on the convulsion time. When the convulsion onset time was more than 60 seconds, the energy was reduced to 20% to 30% of the basic energy; if the convulsion onset time was less than the ideal onset time, the energy was increased to 30% to 50% of the basic energy (Weng, 2002).
Wechsler Memory Scale (WMS) included the following tests: (1)  In addition, the heart rate, blood pressure, and electrocardiogram of patients were assessed before treatment and after 1, 2, 3, and 4 weeks of treatment, so as to evaluate the changes of the above indicators and safety of ECT.
All the clinicians who participated in the scale evaluation received the training before the treatment, and rating scales were administered by trained nurses. The cognitive scales were administered on the days between treatments. The correlation coefficient intraclass correlation coefficient (ICC) value in the group was 0.81 to 0.84, indicating good consistency.

| Evaluation of efficacy
The clinical remission was determined by the reduction rate of the HAMD score. The reduction rate of the HAMD score was classified into the following four grades: ≥75%, 50% to 74%, 25% to 49%, and <25% (considered to be invalid).

| Evaluation of safety
The adverse events during and after treatment were recorded to evaluate the safety of the treatment, such as sustained epilepsy, delirium, prolonged respiratory recovery, sustained hypertension, arrhythmia, headache, nausea and vomiting, myalgia, and so on. At the same time, using the scores of WMS and MMSE, the safety of treatment was evaluated in terms of memory and cognitive function.

| Statistical analysis
SPSS19.0 was used for data statistical analysis. All measurement data were expressed as mean ± SD, and counting data were expressed as n (%). Before and after treatment, paired T test was used for comparison of measurement data, while counting data were examined by χ 2 test. P < .05 was considered a statistically significant difference.

| Evaluation of overall efficacy
We used the HAMD score at week 4 to compare with the pretreatment HAMD score, with a reduction in score of ≥50% as the criterion for efficacy remission.
A total of 43 patients completed the study and their results were showed in the analysis, including 9 cases (20.9%) for the reduced rate of HAMD score grade 75%, 20 cases (46.5%) for reduction rate grade 50% to 74%, 7 cases (16.2%) for reduction rate grade 25% to 49%, 6 cases (13.9%) for reduction rate grade <25%, and the rate of efficacy remission was calculated as 67.44%.

| HAMD scores of patients after ECT treatment were statistically lower than that pretreatment
There was a significant difference in HAMD scores of the patients between before treatment and after 2 weeks of ECT treatment (P < .05). With the progress of treatment, the difference was more significant after 4 weeks of ECT treatment (P < .01). The score of each factor showed that anxiety somatization and sleep disorder were significantly improved after 2 weeks of ECT (P < .05), the scores of depressed mood and behavior and depressive cognitions decreased significantly after 3 weeks of treatment (P < .01), while body weight was not significantly different from pretreatment until the fourth week of ECT (P < .05; Table 1).

| HAMA scores of patients after ECT treatment were statistically lower than that pretreatment
The HAMA scores after 2 weeks of ECT treatment were significantly lower than before treatment (P < .05), and the difference was more significant after 4 weeks of ECT treatment (P < .01). With the progress of treatment, the difference was more significant after 4 weeks of ECT treatment (P < .01). The score of each factor showed that compared with before treatment, mental anxiety improved after 2 weeks of ECT (P < .05), and its scores were more significantly lower after 2 weeks of treatment (P < .01), while there was a significant difference in physical anxiety between before treatment and after 4 weeks of ECT treatment (P < .05; Table 2).

| There were differences in WMS and MMSE scores between before and after ECT treatment
After 1 week of treatment, the scores of memory quotient and immediate memory of WMS were lower than that before treatment with a statistically significant difference (P < .05). After 2 weeks of treatment, except for the significant decrease of immediate memory scores (P < .05), there were no significant differences in scores of memory quotient, long-term memory and short-term memory between before and after treatment (P > .05). Besides, there were no statistical differences in each parameter of WMS between before treatment and after 3 and 4 weeks of treatment (P > .05). Our results found that compared with before treatment, the scores of MMSE significantly increased after 4 weeks of treatment (P < .05; Table 3).

| Adverse events associated with ECT treatment
During the treatment, there was no significant change in heart rate, blood pressure, respiration, SpO 2, and ECG. There were no serious adverse events in any patients, including cardiovascular and cerebrovascular events. Among them, 3 patients had transient hypertension, 4 patients had a slight headache, and no special treatment was conducted. These symptoms relieved spontaneously after resting.

| DISCUSSION
In this study, after ECT treatment, the rate of clinical efficacy was calculated as 67.4%. HAMD scores gradually decreased with the progress of treatment. There was a statistical difference between before treatment and after 2 weeks of ECT treatment, and the difference was more significant after 4 weeks of treatment, suggesting that the treatment was more effective for the improvement of HAMD scores with the course of treatment. Our results showed the scores of anxiety somatization and sleep disorder decreased significantly after 2 weeks of ECT treatment. In this study, the sleep disorder of the patients improved significantly after ECT treatment, which was consistent with the improvement of refractory depression in older patients.
Besides, depressive cognitions and depressed mood and behavior were improved significantly after 3 weeks of treatment.
The results of HAMA showed its total score after 2 weeks of ECT treatment was significantly lower than that before treatment, and a more significant difference was demonstrated after 4 weeks of ECT.
Because of atypical symptoms of older patients with geriatric depression, including anxiety and physical discomfort, the improvement of geriatric depression, especially the refractory depression, is limited.
Our study found HAMA and HAMD scores were improved after 2 weeks of ECT treatment, suggesting that ECT had a certain effect on the treatment for the older patients with refractory depression after 2 weeks of treatment, thereby reducing the risk of suicide and improving the confidence of patients in the treatment. In terms of T A B L E 1 Comparison of HAMD scores between before and after MECT treatment factors of HAMA, physical anxiety was improved later than mental anxiety. The reason may be that the physical anxiety symptoms of elderly patients with refractory depression are too severe to improve quickly, and the recurrence of symptoms also increases the difficulty of treatment and prolongs the process of symptom improvement.
The results of safety showed that the limitation of ECT was due to the comorbidity of various diseases in older patients. There were no serious adverse events in our study, and three patients had transient blood pressure rise and a slight headache, which were relieved by themselves after resting. These results suggested that as long as the risk assessment before treatment, the effective intervention of possible adverse events and postoperative care was carried out for the older patients with refractory depression with comorbidity of somatic diseases, the risks related to ECT treatment of somatic diseases can be reduced, which was consistent with the previous reports (van Schaik et al., 2012).
The effect of ECT on the cognitive function of older patients with refractory depression also needs attention. Studies have shown that the memory fades were found in patients at the end of ECT treatment, but their ability of memory recovered 1 month after treatment, and MMSE scores increased significantly compared with that before treatment. It was also reported that except for the speed of information processing, the high-level cognitive function of patients was not damaged by ECT (Stoppe, Louzã, Rosa, Gil, & Rigonatti, 2006). In our study, after 1 week of treatment, the scores of memory quotient and immediate memory decreased significantly compared with that before treatment, and these events were not be presented with the progress of treatment, except for after 2 weeks of treatment. These results are consistent with the above reports. In addition, there was no significant difference in MMSE scores between before treatment and after 1, 2, and 3 weeks of treatment. However, the score after 4 weeks of treatment was higher than that before treatment, which may be related to the influence of depression on the cognitive disorder of patients. With the improvement of symptoms of depression, the cognitive function of patients has also been improved, but the results of tests cannot exclude the learning effect of multiple measurements.
Although we used an unconventional dosing strategies, we did not compare it with traditional treatment methods in this study, in terms of safety, treatment effect, and so on. Relevant exploration will be carried out in the future study of the treatment of refractory depression in the elderly.

| CONCLUSION
ECT is an effective, well-tolerated, and safe method for the treatment of older patients with refractory depression. It is temporary and reversible for the damage of cognitive function, and this method can be recommended for the treatment of these patients. In addition, the application of ECT is limited due to the somatic comorbidities. Therefore, it is necessary to carry out an assessment of risk before treatment, control relevant risk factors, and strengthen monitoring during and after treatment to ensure the safety of the treatment. In this study, the short term and small sample size can be considered as the limitations of our investigation. Our study only provides a reference for the treatment of older patients with refractory depression, and the maintenance treatment of these patients with refractory depression after the symptoms is relieved and how to prevent the recurrence of depression need further study.

DATA AVAILABILITY STATEMENT
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.