Abstract
Background:
Little information is available on response to electroconvulsive therapy (ECT) in patients with bipolar disorder (BD) from India.
Aim:
This exploratory study aims to evaluate and compare the sociodemographic and clinical profiles, treatment outcomes of BD patients with depression and mania/mixed episode who received ECT and to evaluate the predictors of response to ECT.
Results:
Data of 278 BD patients who received 325 ECT courses were extracted from the ECT register. The number courses of ECT for bipolar depression (n = 202) exceeded those for mania/mixed episodes (n = 123). In terms of response to ECT, >75% response was achieved in 63.3% cases and >50% response was seen in about 90% of the patients. No significant difference was seen in response to ECTs between bipolar depression and mania/mixed episodes.
Conclusion:
The present study suggests that about two-thirds of the BD patients show more than 75% response to ECT, and more than 90% of the BD patients show more than 50% response to ECT.
Keywords: Bipolar disorder, depressive episode, electroconvulsive therapy, manic episode, treatment response
INTRODUCTION
Electroconvulsive therapy (ECT) is one of the effective treatments for bipolar disorder (BD). Although many guidelines mention use of ECT as the third-line treatment for management of BD,[1,2] in Indian settings, it is often used much earlier for faster treatment response.[3]
In terms of response rate, data suggest that the response rate to ECT in bipolar depression is 68.1% and that in mania is 75%, that in the mixed state is 72.9%, and that in catatonia is 80.8%.[4] Data also suggest that ECT is equally effective in patients with bipolar and unipolar depression.[5,6] However, the response rate is faster for patients with BD, when compared to those with unipolar depression, with a lesser number of ECT sessions required to meet the criteria for treatment response.[7] Limited information is available with respect to factors associated with ECT outcome in BD patients.[8,9]
There are limited data on the use of ECT in India. A retrospective study that included data of 67 patients with BD reported that more than 90% of the patients showed more than 50% response and side effects of any kind were noted in about one-fifth (22%) of the patients.[10] However, this study did not evaluate the predictors of response/nonresponse to ECT in BD patients. Another study evaluated the mean motor seizure duration, number of ECTs needed for improvement, and duration of hospital stays after starting ECT and did not report difference on any of the parameters between patients with recurrent depressive disorder and bipolar depression.[11] Considering the limited number of studies and the small sample size of these studies, this exploratory study aims to evaluate and compare the sociodemographic and clinical profiles, treatment outcomes of BD patients with depression and mania/mixed episode and the predictors of response to ECT in BD patients with depression and mania/mixed episode.
METHODOLOGY
This retrospective study was conducted in a tertiary care center and was approved by the ethics committee of the institute in which it was conducted.
At our institute, almost all patients receive bitemporal modified ECT, thrice a week. During the ECT course, patients with affective disorders are rated both clinically and on standardized scales, that is, the Hamilton depression rating scale (HDRS)[12] and the Young mania rating scale (YMRS),[13] at the baseline and during the course of ECT as per the diagnosis. The indications for termination of ECT course include either achievement of clinical remission or plateauing of improvement after two consecutive ECT sessions.
The details of the ECT treatments are penned down in the patient’s treatment record and in the ECT register.
For the purpose of this study, the ECT register of the department was screened to identify the BD patients who were administered ECT between 2014 and March 2023. In our center, during the study period under consideration, patients were diagnosed with BD (current episode depression or mania/mixed episode) as per the international classification of diseases, tenth revision (ICD-10) criteria. If during the study period a patient received ECT more than once for different episodes, the same patient was accounted twice in this study.
Data of all the BD patients who underwent ECT during the period January 2014 to March 2023 were extracted from their treatment records and the ECT register by using a predesigned performa. Response to ECT (determined at the end of the ECT course, irrespective of the number of ECTs given) was categorized based on symptomatic relief >75%, 50–75%, 25–50%, <25%, and no response based on the symptom reduction on the standard scales. Remission was defined as reduction in the HDRS[12] and the YMRS[13] scores to less than 7. Any adverse events/complications related with ECT were also retrieved.
Data were analyzed using SPSS-14. Data representation has been done as numbers and percentages. Central tendency of the data was evaluated in the form of mean and standard deviation. Chi-square and independent samples’ t’ tests were used to compare the sociodemographic and clinical profiles of patients currently in clinical depression and manic/mixed episodes and also to evaluate the predictors of response to ECT.
RESULTS
During the period of 2014 to March, 2023, 1844 courses of ECT were administers, of which 325 (17.6%) were given to those diagnosed with BD. These 325 courses were given to 278 patients.
When the sociodemographic profiles of those who received ECT for manic/mixed episodes and depressive phases of illness were compared, those who received ECT for the manic episodes were significantly younger (P = 0.001) and had a lower proportion of elderly patients (P < 0.001) [Table 1].
Table 1.
Sociodemographic and clinical profiles of BD patients receiving ECT
| Variables | Whole group (n=325) Frequency (%)/Mean (SD) | Depression (n=202) Frequency (%)/Mean (SD) | Manic (n=123) Frequency (%)/Mean (SD) | χ2 test (P) |
|---|---|---|---|---|
| Age | 43.9 (16.05) | 48.8 (15.8) | 35.82 (12.73) | 7.725 (0.001)*** |
| Age >60 years | 64 (19.6%) | 57 (28.2%) | 7 (5.6%) | 24.5 (<0.001)*** |
| Educational status | 10.8 (4.4) | 10.9 (4.4) | 10.6 (4.57) | 0.724 |
| Sex | ||||
| Male | 210 (64.6%) | 128 (63.4%) | 82 (66.7%) | 0.364 (0.55) |
| Female | 115 (35.4%) | 74 (36.6%) | 41 (33.3%) | |
| Religion | ||||
| Hinduism | 208 (64%) | 132 (65.3%) | 76 (61.8%) | 0.42 (0.517) |
| Sikhism | 117 (36%) | 70 (34.6%) | 47 (38.2%) | |
| Socioeconomic status | ||||
| Low | 35 (10.8%) | 17 (8.4%) | 18 (14.6%) | 3.07 (0.079) |
| Middle | 290 (89.2%) | 185 (91.5%) | 105 (85.3%) | |
| Duration of entire illness in months | 339.13 (104.30%) | 221.2 (165.9) | 117.93 (119.9) | U=7625 (<0.001)*** |
| Duration of index episodes in months | 7.1 (2.184%) | 4.8 (4.37) | 2.3 (1.65) | 6.18 (<0.001)*** |
| Presence of psychotic symptoms/syndrome | 158 (48.61%) | 81 (40.1%) | 77 (62.6%) | 15.49 (<0.001)*** |
| Comorbid physical problems | ||||
| None | 195 (60%) | 113 (55.9%) | 82 (66.6%) | 3.664 (0.056) |
| Hypertension | 46 (14.15%) | 30 (14.8%) | 16 (13.1%) | 0.213 (0.64) |
| Hypothyroidism | 11 (3.38%) | 5 (2.4%) | 6 (4.8%) | 1.35 (0.24) |
| Diabetes mellitus | 8 (2.46%) | 4 (1.9%) | 4 (3.2%) | FE=0.48 |
| Chronic obstructive pulmonary disease | 1 (0.307%) | 1 (0.4%) | 0 (0%) | FE=1 |
| Coronary Artery Disease | 1 (0.307%) | 1 (0.4%) | 0 (0%) | FE=1 |
| More than one | 35 (10.76%) | 28 (13.8%) | 7 (6.3%) | 5.3 (0.02)* |
| Others | 28 (8.61%) | 20 (9.9%) | 8 (6.5%) | 1.12 (0.29) |
| Antidepressants | ||||
| TCA’S | 5 (1.53%) | 5 (2.5%) | - | - |
| Escitalopram | 35 (10.76%) | 35 (17.3%) | - | - |
| Sertraline | 12 (3.69%) | 12 (5.9%) | - | - |
| Fluoxetine | 25 (7.69%) | 25 (12.4%) | - | - |
| Venlafaxine | 39 (12%) | 39 (19.3%) | - | - |
| Mirtazapine | 3 (0.92%) | 3 (1.5%) | - | - |
| Bupropion | 17 (5.23%) | 17 (8.4%) | - | - |
| Others | 2 (0.615%) | 2 (1.4%) | - | |
| Antipsychotics | ||||
| Typical (Haloperidol) | 3 (0.92%) | 1 (0.5%) | 2 (1.6%) | FE=0.56 |
| Any Atypical Antipsychotic | 248 (76.3%) | 137 (67.8%) | 111 (90.2%) | 21.2 (<0.001) *** |
| Risperidone | 25 (7.69%) | 15 (7.4%) | 10 (8.1%) | 0.05 (0.82) |
| Olanzapine | 156 (48%) | 79 (39.1%) | 77 (62.6%) | 16.9 (<0.001) *** |
| Quetiapine | 48 (14.76%) | 37 (18.3%) | 11 (8.9%) | 5.33 (0.02)* |
| Clozapine | 5 (1.53%) | 1 (0.5%) | 4 (3.2%) | FE=0.07 |
| Aripiprazole | 8 (2.46%) | 4 (2%) | 4 (3.2%) | FE=0.48 |
| Chlorpromazine | 3 (0.92%) | 0 (0%) | 3 (2.4%) | FE=0.053 |
| More than one antipsychotic | 3 (0.92%) | 1 (0.5%) | 2 (1.6%) | FE=0.56 |
| Mood Stabilizers | ||||
| Any mood stabilizers | 185 (56.9%) | 109 (53.96%) | 76 (61.79%) | 1.91 (0.16) |
| Lithium carbonate | 124 (38.1%) | 76 (37.6%) | 48 (39.1%) | 0.06 (0.80) |
| Sodium valproate | 47 (14.46%) | 22 (10.9%) | 25 (20.3%) | 5.50 (0.02)* |
| Carbamazepine | 4 (1.23%) | 3 (1.5%) | 1 (0.8%) | FE=1 |
| Oxcarbazepine | 3 (0.92%) | 2 (1%) | 1 (0.8%) | FE=1 |
| Lamotrigine | 5 (1.53%) | 5 (2.5%) | 0 (0%) | FE=0.16 |
| More than one mood stabilizer | 2 (0.61%) | 1 (0.5%) | 1 (0.8%) | FE=1 |
| No mood stabilizer | 140 (43.07%) | 93 (46%) | 47 (38.2%) | 1.91 (0.167) |
| Other Medications | ||||
| Anticholinergics | 28 (8.61%) | 12 (5.9%) | 16 (13.1%) | 4.85 (0.02)* |
| Benzodiazepines | 148 (45.5%) | 76 (37.6%) | 72 (58.5%) | 13.48 (<0.001)*** |
*P<0.05; **P<0.01; ***P<0.001. TCAs: Tricyclic Antidepressants
Compared to patients with manic/mixed episodes, patients with current episode depression had a significantly higher proportion of patients with more than one physical comorbidity (P = 0.02), significantly longer duration of illness (P < 0.001), and significantly longer duration of index episodes (P < 0.001). Other clinical details are depicted in Table 1.
In terms of indications for using ECT, there was a significant difference in indication between the two groups on many of the indications [Table 2]. The mean number of ECTs used was slightly higher for the depression subgroup, compared to the mania subgroup, but the difference between the two groups was not significant [Table 2].
Table 2.
Details of ECT treatments
| Variables | Whole group (n=325) Frequency (%)/Mean (SD) | Depression (n=202) Frequency (%)/Mean (SD) | Manic (n=123) Frequency (%)/Mean (SD) | t/χ2 test (P) |
|---|---|---|---|---|
| Indications for ECT | ||||
| Suicidal risk | 131 (40.3%) | 117 (57.9%) | 14 (11.3%) | 68.8 (<0.001) *** |
| Poor oral intake | 64 (19.69%) | 43 (21.3%) | 21 (17.1%) | 0.85 (0.35) |
| Psychomotor Retardation | 45 (13.84%) | 43 (21.3%) | 2 (1.6%) | FE=<0.001*** |
| Catatonia | 21 (6.4%) | 21 (10.4%) | 0 (0%) | - |
| Poor response to medication | 227 (69.8%) | 140 (69.3%) | 87 (70.7%) | 0.073 (0.78) |
| Considered treatment of choice | 130 (40%) | 74 (36.6%) | 56 (45.5%) | 2.52 (0.11) |
| Requirement of early response | 193 (59.38%) | 103 (51%) | 90 (73.1%) | 15.59 (<0.001) *** |
| Contraindication to medication | 23 (7.07%) | 14 (6.9%) | 9 (7.3%) | 0.0174 (0.89) |
| ECT Treatments | ||||
| Mean number of ECT treatment | 7.01 (2.9) | 7.13 (3.05) | 6.9 (3.1) | 0.446 (0.656) |
| Motor seizure duration in seconds | 30.3 (14.5) | 28.57 (12.3) | 29.05 (12.2) | -0.338 (0.735) |
| Response to ECT | ||||
| >75% | 210 (64.61%) | 128 (63.3%) | 82 (66.6%) | 0.36 (0.54) |
| >50% | 298 (91.69%) | 186 (92.1%) | 112 (91.0%) | 0.104 (0.74) |
| 25-50% | 12 (36.9%) | 7 (3.5%) | 5 (4.1%) | 0.077 (0.78) |
| <25% | 5 (1.53%) | 3 (1.5%) | 2 (1.6%) | FE=1 |
| No response | 10 (3.07%) | 6 (3%) | 4 (3.2%) | FE=1 |
| Remission | 175 (53.84%) | 102 (50.4%) | 73 (59.34%) | 2.4 (0.12) |
| Adverse events with ECT | ||||
| Aches and pains | 23 (7.07%) | 12 (5.9%) | 11 (8.9%) | 1.048 (0.30) |
| Delirium | 14 (4.3%) | 9 (4.5%) | 5 (4.1%) | 0.02 (0.86) |
| Switch | 3 (0.92%) | 1 (5%) | 2 (1.6%) | FE=0.55 |
| Cognitive deficits for hours to days | 37 (11.38%) | 20 (10%) | 17 (13.8%) | 1.16 (0.28) |
| Injury | 3 (0.92%) | 1 (5%) | 2 (1.6%) | FE=0.55 |
| Immediate complications | ||||
| Acute blood pressure changes | 74 (22.76%) | 53 (26.2%) | 21 (17.1%) | 3.65 (0.056) |
| Electrocardiogram changes | 16 (4.92%) | 11 (5.4%) | 5 (4.1%) | 0.31 (0.57) |
| Hypoxia | 5 (1.53%) | 4 (2.0%) | 1 (0.8%) | FE=0.653 |
| Others | 14 (4.30%) | 12 (5.9%) | 2 (1.6%) | FE=0.089 |
| No Complications | 216 (66.46%) | 122 (60.4%) | 94 (76.4%) | 8.8 (<0.001) *** |
*P<0.05; **P<0.01; ***P<0.001
When an attempt was made to evaluate the predictors of >75% response to ECT, among the patients with current episode depression, a significantly higher proportion of responders had suicidality (Chi-square value 6.9; P = 0.009**) as an indication for ECT, whereas catatonia (Chi-square value 4.24; P = 0.039) as an indication for use of ECT was associated with poor response to ECT. Compared to responders, nonresponders had significantly higher severity of baseline HDRS score (t = 2.08; P = 0.038*) and received a higher number of effective ECTs (t = 1.93; P = 0.05*), had current symptoms for longer duration (t = 2.28; P = 0.024*), and longer duration of illness (t = 3.82; P < 0.001***). Compared to responders, a higher proportion of nonresponders had at least one complication with ECT (Chi-square value = 3.99; P = 0.046*) and developed delirium (Chi-square value = 3.75; P = 0.05*), whereas aches/pains were significantly higher in responders (Chi-square value = 4.4; P = 0.036*).
In terms of predictors of >75% response to ECT among the patients with current episode mania/mixed episodes, a significantly higher proportion of responders were inpatients at the time of receiving ECT (Chi-square value 13.72; P = 0.000), had presence of motor symptoms (psychomotor retardation) as an indication for ECT (Chi-square value 63.7; P = 0.0053), and received a significantly higher number of ECT (t 2.98; P = 0.004**).
In the whole sample, the presence of catatonia (Chi-square value 4.6; P = 0.03) as an indication for ECT was associated with poor response to ECT.
DISCUSSION
In the present study, in the depression group, the most common indication for ECT was poor response to medications, followed by suicidal risk, the requirement of early response, ECT considered as the treatment of choice, poor oral intake, psychomotor retardation, and catatonia. This profile of indication for ECT in the currently depressed group was slightly different in terms of the common indications for ECT (most common: retardation/agitation, followed by ECT considered treatment of choice, suicidal risk, poor response to medication, psychotic symptoms, and poor oral intake) reported in the previous study from our center.[10] The findings in terms of indications for ECT, align with the recommendations to use of ECT in BD patients in different treatment guidelines.[14] In the mania/mixed episode group, the most common indication for ECT was a requirement of early response, followed by poor response to medication, ECT considered as the treatment of choice, and poor oral intake. The use of ECT for early response could be attributed to presence of agitation/aggression and a higher prevalence of psychotic symptoms in the mania/mixed episode.
In the present study, in both the subgroups, more than half of the patients achieved >75% response and when the response was defined by a reduction in symptoms by >50%, slightly more than 90% of the patients in both the subgroups showed response to ECT. A recent study reported the response rate in bipolar depression to be 68.1% and that in mania to be 75%, that in mixed episodes to be 72.9%, and that in catatonia to be 80.8%.[9] Our findings are similar to those of the previous Indian study[10] and are higher than those of the study from Italy.[9] This difference in response across different countries could be attributed to the clinical profile of the patients and stage (i.e., level of treatment resistance at the time of consideration of ECT) at which ECT was considered.
As more than 90% of patients in both the subgroups showed response to ECT, for evaluating the predictors of response to ECT, we compared the patients who showed more than and less than 75% response to ECT. Existing literature suggests that the presence of a comorbid obsessive-compulsive disorder or personality disorder, history of receiving lamotrigine longer duration of the current episode, and higher severity of illness are associated with lower treatment response.[8,9] Unfortunately, in the present study, we did not have information about psychiatric comorbidity for our study sample. Hence, it is not possible to compare the findings with the those of the existing literature. In the present study, catatonia as an indicator for ECT was associated with poor response (80%) to ECT. This finding was also surprising for us, considering the fact that it is contrary to existing literature that suggests that catatonia in general is associated with good response to ECT. This finding suggests that there is a need to further evaluate the response to ECT in bipolar patients.
Additionally, nonresponders had significantly higher severity of the current episode at the time of considering ECT and received a higher number of effective ECTs and had longer duration of current symptoms and longer duration of illness. Accordingly, it can be said that our findings do support the exiting literature on nonresponse of ECT being related to higher severity of illness and longer duration of illness.[8,9] Other findings of nonresponse to ECT being related to use of a higher number of ECTs possibly indicate that clinicians often continue to give a few extra sessions of ECT in nonresponders expecting a late response.
In the present study, adverse effects related to ECT were reported by about one-third of the patients with acute blood pressure changes being the most common complications. In terms of other adverse effects, cognitive deficits were noted in only about one-ninth of the study sample. This is much lower than that reported in a previous study from this center.[10] A systematic review found cognitive impairment as a problem in only one out of six studies evaluating the level of cognitive deficits among BD patients receiving ECT.[15] In some of the studies included in the systematic review, the cognitive deficits among patients receiving ECT were compared with those among patients on lithium, other medications, and normal controls, and these studies showed no significant difference between the ECT group and medication groups. However, BD patients irrespective of the intervention performed poorly than normal controls.[15] Studies that compared pre- and post-ECT cognitive functions showed improvement, no change, or worsening of cognitive functioning after ECT.[15] The prevalence of cognitive adverse effects in about 11% in the present study possibly suggests that some of the patients experience worsening of symptoms, whereas others do not experience significant impairment.
The present study has certain limitations, which must be kept in mind while interpreting the findings. First, this was a retrospective study and relied on the available data in the ECT register. Despite ensuring the completeness of the data, it is possible that some of the data could have been missed. Second, the cognitive side effects were not assessed using any standardized scale to assess autobiographic memory. Hence, this could have led to underestimation of the cognitive side effects. Third, we did not have information about the exact age or history of past ECT treatment. Third, we did not evaluate the information about the longitudinal course of illness before ECT. This could influence the prescription pattern. We also did not have information on the level of treatment resistance before consideration of ECT.
To conclude, the present study suggests that about one-sixth of the ECT courses are received by BD patients. Bipolar depression forms a more common indication for ECT, when compared to bipolar mania/mixed episodes. In general, the response to ECT in BD is good, with about two-thirds of the patients showing more than 75% response to ECT and more than 90% patients showing more than 50% response to ECT. Only 11% of the BD patients receiving ECT develop cognitive adverse effects.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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