Asian Journal of Psychiatry 8 (2014) 43–46
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Efficacy of ECT in bipolar and unipolar depression in a real life hospital setting Janardhanan C. Narayanaswamy *, Biju Viswanath, Preethi V. Reddy, K. Raghavendra Kumar, Jagadisha Thirthalli, Bangalore N. Gangadhar Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore 560029, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 January 2013 Received in revised form 5 October 2013 Accepted 9 October 2013
Background: It has been debated as to whether the polarity of mood disorder (bipolar versus unipolar) has prognostic significance for electroconvulsive therapy (ECT) outcome. In the treatment guidelines, ECT is recommended more readily for unipolar depression and not so for bipolar depression. This study aims to examine efficacy of bipolar and unipolar depression to ECT in a real life naturalistic setting. Method: We studied the ECT parameters of all consecutive patients with a diagnosis of unipolar depression (recurrent depressive disorder, 2 episodes of depression) and bipolar depression referred for ECT between the months of July 2008 and December 2010 (BP-D: n = 44) and (UP-D: n = 106). Results: When bipolar depression was compared to unipolar depression, the average motor seizure duration (mean = 46.9 and 46.7, t = 0.06, p = 0.94), number of ECTs required for improvement (mean = 6.4 and 6.5, t = 0.17, p = 0.86), duration of inpatient stay after ECT initiation in days (mean = 16.2 and 16.6, t = 0.23, p = 0.81) and improvement as assessed using a Likert scale (Mann–Whitney U, Z = 0.09, p = 0.92) were not statistically different between the groups. Conclusions: We did not find any difference in efficacy of ECT between the two forms of depression in real life setting. This calls for justification of use of ECT in all patients with depression irrespective of the type of illness polarity and inclusion of ECT as a routine treatment option in bipolar depression guidelines. ß 2013 Elsevier B.V. All rights reserved.
Keywords: Electroconvulsive therapy Unipolar depression Bipolar depression
1. Introduction Electroconvulsive therapy (ECT) is a somatic treatment option that has been extensively validated for the treatment of unipolar depression and has also been used for the treatment of both manic and depressive bipolar states. Mood disorders are divided into unipolar (UP) depression and bipolar (BP) depression according to the presence or history of a manic or hypomanic episode (APA, 1994). Based on the cross sectional clinical profile, there are no pathognomonic characteristics of bipolar depression compared to unipolar depression (Mitchell et al., 2008). However, the treatment guidelines for UP depression encourage the use of SSRIs as first line of treatment (APA, 2000). For BP depression mood stabilizers and atypical antipsychotics are considered primarily, while a word of caution is mentioned regarding antidepressant monotherapy for the fear of switch to the opposite pole (Suppes et al., 2002; Yatham et al., 2006).
* Corresponding author. Tel.: +91 9481475125. E-mail addresses: [email protected], [email protected] (J.C. Narayanaswamy). 1876-2018/$ – see front matter ß 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajp.2013.10.006
In this manner, ECT does not form an important treatment option in bipolar depression according to the treatment guidelines. It is most often reserved for patients who do not respond to other forms of treatment and it figures at the end of the algorithm (APA, 2002; Fountoulakis et al., 2008). However, a recent body of evidence suggests that ECT could be useful in BP depression (Bailine et al., 2010; Sienaert et al., 2009). A recent meta-analysis which included six studies examining this aspect reveals that the response to ECT and the corresponding rates of remission was similar in bipolar and unipolar forms of depression (Dierckx et al., 2012). Hence there is a discrepancy in the evidence according to the literature and its translation into clinical guidelines. One also needs to examine this question without the stringent criteria of subject recruitment as seen with controlled trials, in order to interpret the results in a meaningful way closer to the clinical and real world scenario. In addition, there could be differences based on the different clinical populations between different parts of the world. For instance, indications for ECT (refractory depression vs. as a first line choice), age of the patient population etc. could be different across various study cohorts. In this study we sought to examine the efficacy of ECT in bipolar depression compared to unipolar depression in a larger sample of inpatients. More
44
J.C. Narayanaswamy et al. / Asian Journal of Psychiatry 8 (2014) 43–46
importantly we sought to examine the benefit of ECT between both the types of depression in a hospital setting with ECT parameters supplemented with hospitalization indices. This would provide an understanding about the real life setting difference of the effectiveness of ECT between both the forms of depression. 2. Methods 2.1. Setting National Institute of Mental Health and Neurosciences, Bangalore is a tertiary care psychiatric Institute in South India with a bed-strength of 550. Annually, about 500 patients are prescribed ECTs, of which most are inpatients. All patients are evaluated by a multi-disciplinary mental health team under the supervision of academic faculty. ICD-10 criteria are used to diagnose the psychiatric disorders. Consistent with the practice in the rest of the developing countries, the need to reduce the number of days of hospital stay with the hope of rapid response forms an important indication for starting ECTs (Chanpattana et al., 2005). The ECT team consists of psychiatrists, anesthetists, ECT nurses, dedicated staff and a state-of-the-art ECT suite. Each patient undergoes a pre-ECT evaluation consisting of detailed psychiatric and medical history, clinical examination with particular emphasis on neuropsychiatric aspects, pertinent laboratory investigations and, where necessary, ECG as well as brain imaging. Seizure threshold is determined during the first ECT session by the titration method (Scott, 2005). During the course of ECT, if seizures are not elicited at electrical stimulus that was used during an earlier session, then the new threshold is determined by titration method again, starting from the previously used electrical dose. Treatment is administered using a NIVIQURE machine (Technonivilak, Bangalore, India). Brief-pulse stimulus is delivered with constant current at 800 mA, with a frequency of 125 pulses per second (62.5 Hz) and pulse width of 1.5 ms; the duration of train is altered to adjust the dose. All ECTs are administered under anesthetic modification (thiopentone 3–4 mg/kg and succinylcholine 0.5– 1 mg/kg). Cuff-method is used to record the duration of motor seizures. The details of indications for ECT, seizure threshold, duration of seizures and ECT-related complications are documented in the case-records. Changes in the clinical picture of the patients are recorded by the nurses, psychiatry postgraduate resident doctors, senior registrars and consultant psychiatrists. The
referring psychiatrists decide on the number of ECTs for each patient – the reason for stopping ECT (clinical improvement/ complication/withdrawal of consent, etc.) are noted in the file. 2.2. Sample We studied the records of patients with bipolar affective disorder in an episode of depression (BP depression, n = 44) and patients with recurrent depressive disorder (UP depression with 2 episodes of depression, n = 106) as per ICD 10, referred for ECT between the months of July 2008 and December 2010. All Patients received bilateral ECTs at 1.5 times the threshold stimulus dose. 2.3. Outcome measures Clinical improvement and seizure parameters formed the measures of outcome. Two raters (JCN and BV) studied the records and rated the severity using the clinical global impressions scale (CGI). The overall improvement was rated using a five point Likert scale (1, 20% improvement or less; 2, 20–40% improvement; 3, 40– 60% improvement; 4, 60–80% improvement; 5, 80–100% improvement) based on the CGI pre-post comparison. The inter-rater reliability between them was good on 20 randomly selected records (kappa = 0.67, p < 0.01). The number of ECT sessions received by the patients was used as a measure of speed of response, as the reason for stopping ECT was achievement of clinically significant improvement in all patients of both groups. An important reason for which ECT is prescribed in this setting is to shorten the hospital stay. In this background, the number of days of hospital stay following initiation of ECT was also considered as an outcome measure. 2.4. Statistical analysis Statistical analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 13.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were analyzed using the independent sample t test; categorical variables were analyzed using the chi-square test. To control for the potential confounding effects of age of onset, concurrent use of anticonvulsants and severity measured by CGI on the outcome variable (number of ECTs), multiple linear regression analysis was used. The improvement level from the Likert scale was analyzed using the Mann–Whitney U test.
Table 1 Comparison of demographic and clinical variables between bipolar (BP) (N = 44) and unipolar (UP) (N = 106) depression. BP depression (n = 44), mean values (SD) Mean age in years (SD) Mean age of onset of illness in years (SD) Females [n (%)] Bitemporal electrode placement (rest were bifrontal) [n (%)] Comorbid psychiatric diagnoses [n (%)] Melancholic symptoms [n (%)] Suicidal ideations [n (%)] Psychotic symptoms [n (%)] Mean duration of treatment before ECT in days (SD) Weight in kilograms (SD) Indications for ECT [n (%)] As a first line therapy To augment pharmacotherapy/medication resistant Clinical global impression – severity at the start of ECT sessions (SD) Thiopentone – mg (SD) Succinylcholine – mg (SD) Concurrent use of anti-epileptics [n (%)] P-value < 0.05 is considered statistically significant. t-independent samples t test.
32.6 (10.9) 24.3 (8.5) 24 (54.5) 40 (90.9) 9 (20.5) 24 (54.5) 25 (56.8) 29 (65.9) 4.2 (4.6) 57.1 (12.9) 32 (72.5) 12 (27.3) 5.4 (0.6) 172.3(39.3) 29.6 (6.8) 6 (13.6)
UP depression-(n = 106), mean values (SD)
t/chi-square
p
36.1 (13.5) 30.3 (13.2) 50 (47.2) 91 (86.7) 18 (17.0) 63 (59.4) 80 (75.5) 52 (49.1) 4.8 (4.9) 55.8 (14.1)
1.48 2.79 0.67 0.52 0.25 0.77 5.15 3.55 0.76 0.52
0.13 0.001 0.41 0.46 0.61 0.67 0.23 0.06 0.44 0.59
83 (78.3) 23 (27.1) 5.7 (0.6) 163.4 (42.0) 29.5 (8.0) 1 (1.0)
0.46
0.42
0.09 1.20 0.09 11.14
0.04 0.23 0.93 0.001
J.C. Narayanaswamy et al. / Asian Journal of Psychiatry 8 (2014) 43–46
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Table 2 Comparison of ECT related and outcome variables between bipolar (BP) (N = 44) and unipolar (UP) (N = 106) depression. BP depression-(n = 44), mean values (SD) Clinical variables Number of ECTs Duration of inpatient stay after ECT initiation in days Improvement as per Likert scale
6.4 (2.4) 16.2 (9.1) 3.5 (1.1)
Seizure-related variables Threshold at first ECT in milli-coulombs Second threshold in milli-coulombs (n = 33 and 88 for BP and UP patients respectively) Third threshold in milli-coulombs (n = 12 and 27 for BP and UP patients respectively) Number of failed sessions to induce seizures Average duration of motor seizure in seconds
88.6 161.8 230.0 0.1 46.9
(75.1) (109.7) (84.2) (0.5) (14.0)
UP depression-(n = 106) mean values (SD) 6.5 (2.1) 16.6 (9.2) 4.0 (0.9)
83.2 152.0 258.8 0.1 46.7
(61.4) (80.3) (103.6) (0.3) (13.5)
t/chi-square/z
p
0.17 0.23 0.09
0.86 0.81 0.92
0.46 0.53 0.84 0.30 0.06
0.64 0.59 0.40 0.75 0.94
P value < 0.05 is considered statistically significant. z-Mann–Whitney U test; t-independent samples t test.
3. Results Table 1 shows the socio-demographic and clinical details of the study sample. BP depression group had the illness onset significantly earlier than UP depression group. However, there was no significant difference in the current age of patients in both these groups. Among the clinical characteristics, unipolar depression group had significantly higher occurrence of suicidality. The severity of illness according to the initial CGI measure was higher in UP depression group. The sample was comparable in other details like gender, electrode placement (bifrontal vs. bitemporal), presence of psychiatric comorbidities and other clinical characteristics. Similarly, groups were comparable in the indications for which ECT was initiated. The BP depression group had significantly higher use of anticonvulsants during the course of ECT. Table 2 shows the differences in the two groups in outcome variables. There was no significant difference between the groups in the number of ECTs received, seizure threshold at the first and subsequent sessions, number of failed attempts at seizure induction, the duration of hospital stay after initiation of ECTs and the improvement as per the likert scale. Multiple linear regression analysis was performed with the number of ECTs as dependent variable and the groups (BP depression and UP depression), age of onset and severity of illness as assessed by CGI as independent variables. The model was not significant (F = 0.99, p = 0.41). There were no major treatment emergent adverse effects noted. 4. Discussion The main purpose of the study was to elucidate whether there is a perceptible difference in efficacy of ECT between BP and UP depression groups. There was no difference between the groups in treatment efficacy with ECT in the present study as measured by the number of ECTs required, CGI severity at the end of treatment and the rating with Likert scale. Similarly, the groups did not show any difference based on failed ECT attempts and ECT days. Some of the earlier studies with a retrospective chart review design found that ECT had equivalent efficacy in BP and UP depressed patients (Abrams and Taylor, 1974; Avery and Winokur, 1977; Black et al., 1986). However, there are contrasting reports of higher efficacy in UP (Homan et al., 1982) and BP (Perris and d’Elia, 1966) groups. Recent studies conducted in a prospective manner have shown equal efficacy (Bailine et al., 2010; Daly et al., 2001; Sienaert et al., 2009) between groups. Daly and colleagues, using double-blind treatment protocol, examined the treatment efficacy with ECT between UP (n = 162) and BP depression (n = 66) (Daly et al., 2001). Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Patients with BP and
UP depression did not differ in rates of response or remission following the ECT course. However, in this study, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. In more recent double blind studies by Sienaert et al. (13 patients with BP and 51 patients with UP depression) and Bailine et al. (50 patients with BP and 170 patients with UP depression) ECT had equal efficacy (Bailine et al., 2010; Sienaert et al., 2009). However, both these studies reported a more rapid response in BP depression. In line with most observations, we found no difference between BP and UP patients in likelihood of response or degree of symptomatic improvement following the ECT course. ECT has been reported to be associated with provocation of a hypomanic or manic episode in BP depressed patients (Devanand et al., 1988). However, no patients in the present study developed a treatment emergent manic/hypomanic switch with ECT. Similarly, there were no serious untoward complications noted with ECT in either groups requiring treatment discontinuation. This being a chart-based study, the findings could have been biased by confounding factors. Age of onset of illness, concurrent use of anticonvulsants and severity of illness as measured by CGI severity were statistically different between the groups. Earlier age of onset in bipolar illness in documented earlier (Solomon et al., 2006). Since the severity of illness is higher in UP depression group, it could be argued that this could have leveled any possible efficacy favoring unipolar depression. Multiple linear regression analysis was done to control for these confounding factors and it was nonsignificant. Thus, these confounds may not explain the outcome. The absence of standardized methods of assessing the severity of illness (like standardized scales for assessing the severity) and adverse effects limits the interpretation of our study. However, number of ECTs administered to achieve clinically significant improvement and the number of hospital days form meaningful outcome measures – a previous study from our center has used similar measures (Hiremani et al., 2008). Examining the difference of efficacy in uncontrolled hospital setting coupled with inclusion of hospitalization indices would enable the results to be interpreted in the real world setting. Further, the fact that two raters who were blind to each others’ scores achieved a high reliability in their CGI and Likert scale scores partially validated this as a measure of meaningful clinical outcome. One more potential limitation is the absence of EEG seizure monitoring method in this study. The method using motor seizure parameters has been a useful and practical method in settings like ours where many patients receive ECT sessions daily. In that context, even though the ECT method of seizure monitoring appears superior, the motor seizure monitoring method appears more practical. Bipolar depression continues to be a condition with lesser response to the antidepressant medications, with a potential risk
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for switch to mania. There are many challenges in the treatment of BP depression where newer treatment strategies are being tried. ECT is efficacious and is not associated with any significant safety issues in BP depression which is similar to the use in UP depression. However, the present guidelines need to recognize the role of ECT in bipolar depression. Instead of reserving this option for refractory cases, it is prudent to consider it as an important clinical option wherever the resources are available. Conflict of interest None. References Abrams, R., Taylor, M.A., 1974. Unipolar and bipolar depressive illness: phenomenology and response to electroconvulsive therapy. Arch. Gen. Psychiatry 30, 320–321. APA, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Association, Washington, DC. APA, 2000. Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, 2nd ed. American Psychiatric Association, Washington, DC. APA, 2002. Treatment of Patients with Bipolar Disorder, 2nd ed. American Psychiatric Association, Washington, DC. Avery, D., Winokur, G., 1977. The efficacy of electroconvulsive therapy and antidepressants in depression. Biol. Psychiatry 12, 507–523. Bailine, S., Fink, M., Knapp, R., Petrides, G., Husain, M.M., Rasmussen, K., Sampson, S., Mueller, M., McClintock, S.M., Tobias, K.G., Kellner, C.H., 2010. Electroconvulsive therapy is equally effective in unipolar and bipolar depression. Acta Psychiatr. Scand. 121, 431–436. Black, D.W., Winokur, G., Nasrallah, A., 1986. ECT in unipolar and bipolar disorders: a naturalistic evaluation of 460 patients. Convuls. Ther. 2, 231–237. Chanpattana, W., Kunigiri, G., Kramer, B.A., Gangadhar, B.N., 2005. Survey of the practice of electroconvulsive therapy in teaching hospitals in India. J. ECT 21, 100–104.
Daly, J.J., Prudic, J., Devanand, D.P., Nobler, M.S., Lisanby, S.H., Peyser, S., Roose, S.P., Sackeim, H.A., 2001. ECT in bipolar and unipolar depression: differences in speed of response. Bipolar Disord. 3, 95–104. Devanand, D.P., Sackeim, H.A., Decina, P., Prudic, J., 1988. The development of mania and organic euphoria during ECT. J. Clin. Psychiatry 49, 69–71. Dierckx, B., Heijnen, W.T., van den Broek, W.W., Birkenhager, T.K., 2012. Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a metaanalysis. Bipolar Disord. 14, 146–150. Fountoulakis, K.N., Grunze, H., Panagiotidis, P., Kaprinis, G., 2008. Treatment of bipolar depression: an update. J. Affect. Disord. 109, 21–34. Hiremani, R.M., Thirthalli, J., Tharayil, B.S., Gangadhar, B.N., 2008. Double-blind randomized controlled study comparing short-term efficacy of bifrontal and bitemporal electroconvulsive therapy in acute mania. Bipolar Disord. 10, 701–707. Homan, S., Lachenbruch, P.A., Winokur, G., Clayton, P., 1982. An efficacy study of electroconvulsive therapy and antidepressants in the treatment of primary depression. Psychol. Med. 12, 615–624. Mitchell, P.B., Goodwin, G.M., Johnson, G.F., Hirschfeld, R.M., 2008. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord. 10, 144–152. Perris, C., d’Elia, G., 1966. A study of bipolar (manic-depressive) and unipolar recurrent depressive psychoses IX: therapy and prognosis. Acta Psychiatr. Scand. Suppl. 194, 153–171. Scott, A.I.F., 2005. Practical administration of ECT. In: Scott, A.I.F. (Ed.), The ECT Hand Book. The Royal College of Psychiatrists, London, pp. 144–158. Sienaert, P., Vansteelandt, K., Demyttenaere, K., Peuskens, J., 2009. Ultra-brief pulse ECT in bipolar and unipolar depressive disorder: differences in speed of response. Bipolar Disord. 11, 418–424. Solomon, D.A., Leon, A.C., Maser, J.D., Truman, C.J., Coryell, W., Endicott, J., Teres, J.J., Keller, M.B., 2006. Distinguishing bipolar major depression from unipolar major depression with the screening assessment of depression-polarity (SAD-P). J. Clin. Psychiatry 67, 434–442. Suppes, T., Dennehy, E.B., Swann, A.C., Bowden, C.L., Calabrese, J.R., Hirschfeld, R.M., Keck Jr., P.E., Sachs, G.S., Crismon, M.L., Toprac, M.G., Shon, S.P., 2002. Report of the Texas Consensus Conference Panel on medication treatment of bipolar disorder 2000. J. Clin. Psychiatry 63, 288–299. Yatham, L.N., Kennedy, S.H., O’Donovan, C., Parikh, S.V., MacQueen, G., McIntyre, R.S., Sharma, V., Beaulieu, S., 2006. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007. Bipolar Disord. 8, 721–739.
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Efficacy of ECT in bipolar and unipolar depression in a real life hospital setting Janardhanan C. Narayanaswamy *, Biju Viswanath, Preethi V. Reddy, K. Raghavendra Kumar, Jagadisha Thirthalli, Bangalore N. Gangadhar Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore 560029, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 January 2013 Received in revised form 5 October 2013 Accepted 9 October 2013
Background: It has been debated as to whether the polarity of mood disorder (bipolar versus unipolar) has prognostic significance for electroconvulsive therapy (ECT) outcome. In the treatment guidelines, ECT is recommended more readily for unipolar depression and not so for bipolar depression. This study aims to examine efficacy of bipolar and unipolar depression to ECT in a real life naturalistic setting. Method: We studied the ECT parameters of all consecutive patients with a diagnosis of unipolar depression (recurrent depressive disorder, 2 episodes of depression) and bipolar depression referred for ECT between the months of July 2008 and December 2010 (BP-D: n = 44) and (UP-D: n = 106). Results: When bipolar depression was compared to unipolar depression, the average motor seizure duration (mean = 46.9 and 46.7, t = 0.06, p = 0.94), number of ECTs required for improvement (mean = 6.4 and 6.5, t = 0.17, p = 0.86), duration of inpatient stay after ECT initiation in days (mean = 16.2 and 16.6, t = 0.23, p = 0.81) and improvement as assessed using a Likert scale (Mann–Whitney U, Z = 0.09, p = 0.92) were not statistically different between the groups. Conclusions: We did not find any difference in efficacy of ECT between the two forms of depression in real life setting. This calls for justification of use of ECT in all patients with depression irrespective of the type of illness polarity and inclusion of ECT as a routine treatment option in bipolar depression guidelines. ß 2013 Elsevier B.V. All rights reserved.
Keywords: Electroconvulsive therapy Unipolar depression Bipolar depression
1. Introduction Electroconvulsive therapy (ECT) is a somatic treatment option that has been extensively validated for the treatment of unipolar depression and has also been used for the treatment of both manic and depressive bipolar states. Mood disorders are divided into unipolar (UP) depression and bipolar (BP) depression according to the presence or history of a manic or hypomanic episode (APA, 1994). Based on the cross sectional clinical profile, there are no pathognomonic characteristics of bipolar depression compared to unipolar depression (Mitchell et al., 2008). However, the treatment guidelines for UP depression encourage the use of SSRIs as first line of treatment (APA, 2000). For BP depression mood stabilizers and atypical antipsychotics are considered primarily, while a word of caution is mentioned regarding antidepressant monotherapy for the fear of switch to the opposite pole (Suppes et al., 2002; Yatham et al., 2006).
* Corresponding author. Tel.: +91 9481475125. E-mail addresses: [email protected], [email protected] (J.C. Narayanaswamy). 1876-2018/$ – see front matter ß 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajp.2013.10.006
In this manner, ECT does not form an important treatment option in bipolar depression according to the treatment guidelines. It is most often reserved for patients who do not respond to other forms of treatment and it figures at the end of the algorithm (APA, 2002; Fountoulakis et al., 2008). However, a recent body of evidence suggests that ECT could be useful in BP depression (Bailine et al., 2010; Sienaert et al., 2009). A recent meta-analysis which included six studies examining this aspect reveals that the response to ECT and the corresponding rates of remission was similar in bipolar and unipolar forms of depression (Dierckx et al., 2012). Hence there is a discrepancy in the evidence according to the literature and its translation into clinical guidelines. One also needs to examine this question without the stringent criteria of subject recruitment as seen with controlled trials, in order to interpret the results in a meaningful way closer to the clinical and real world scenario. In addition, there could be differences based on the different clinical populations between different parts of the world. For instance, indications for ECT (refractory depression vs. as a first line choice), age of the patient population etc. could be different across various study cohorts. In this study we sought to examine the efficacy of ECT in bipolar depression compared to unipolar depression in a larger sample of inpatients. More
44
J.C. Narayanaswamy et al. / Asian Journal of Psychiatry 8 (2014) 43–46
importantly we sought to examine the benefit of ECT between both the types of depression in a hospital setting with ECT parameters supplemented with hospitalization indices. This would provide an understanding about the real life setting difference of the effectiveness of ECT between both the forms of depression. 2. Methods 2.1. Setting National Institute of Mental Health and Neurosciences, Bangalore is a tertiary care psychiatric Institute in South India with a bed-strength of 550. Annually, about 500 patients are prescribed ECTs, of which most are inpatients. All patients are evaluated by a multi-disciplinary mental health team under the supervision of academic faculty. ICD-10 criteria are used to diagnose the psychiatric disorders. Consistent with the practice in the rest of the developing countries, the need to reduce the number of days of hospital stay with the hope of rapid response forms an important indication for starting ECTs (Chanpattana et al., 2005). The ECT team consists of psychiatrists, anesthetists, ECT nurses, dedicated staff and a state-of-the-art ECT suite. Each patient undergoes a pre-ECT evaluation consisting of detailed psychiatric and medical history, clinical examination with particular emphasis on neuropsychiatric aspects, pertinent laboratory investigations and, where necessary, ECG as well as brain imaging. Seizure threshold is determined during the first ECT session by the titration method (Scott, 2005). During the course of ECT, if seizures are not elicited at electrical stimulus that was used during an earlier session, then the new threshold is determined by titration method again, starting from the previously used electrical dose. Treatment is administered using a NIVIQURE machine (Technonivilak, Bangalore, India). Brief-pulse stimulus is delivered with constant current at 800 mA, with a frequency of 125 pulses per second (62.5 Hz) and pulse width of 1.5 ms; the duration of train is altered to adjust the dose. All ECTs are administered under anesthetic modification (thiopentone 3–4 mg/kg and succinylcholine 0.5– 1 mg/kg). Cuff-method is used to record the duration of motor seizures. The details of indications for ECT, seizure threshold, duration of seizures and ECT-related complications are documented in the case-records. Changes in the clinical picture of the patients are recorded by the nurses, psychiatry postgraduate resident doctors, senior registrars and consultant psychiatrists. The
referring psychiatrists decide on the number of ECTs for each patient – the reason for stopping ECT (clinical improvement/ complication/withdrawal of consent, etc.) are noted in the file. 2.2. Sample We studied the records of patients with bipolar affective disorder in an episode of depression (BP depression, n = 44) and patients with recurrent depressive disorder (UP depression with 2 episodes of depression, n = 106) as per ICD 10, referred for ECT between the months of July 2008 and December 2010. All Patients received bilateral ECTs at 1.5 times the threshold stimulus dose. 2.3. Outcome measures Clinical improvement and seizure parameters formed the measures of outcome. Two raters (JCN and BV) studied the records and rated the severity using the clinical global impressions scale (CGI). The overall improvement was rated using a five point Likert scale (1, 20% improvement or less; 2, 20–40% improvement; 3, 40– 60% improvement; 4, 60–80% improvement; 5, 80–100% improvement) based on the CGI pre-post comparison. The inter-rater reliability between them was good on 20 randomly selected records (kappa = 0.67, p < 0.01). The number of ECT sessions received by the patients was used as a measure of speed of response, as the reason for stopping ECT was achievement of clinically significant improvement in all patients of both groups. An important reason for which ECT is prescribed in this setting is to shorten the hospital stay. In this background, the number of days of hospital stay following initiation of ECT was also considered as an outcome measure. 2.4. Statistical analysis Statistical analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 13.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were analyzed using the independent sample t test; categorical variables were analyzed using the chi-square test. To control for the potential confounding effects of age of onset, concurrent use of anticonvulsants and severity measured by CGI on the outcome variable (number of ECTs), multiple linear regression analysis was used. The improvement level from the Likert scale was analyzed using the Mann–Whitney U test.
Table 1 Comparison of demographic and clinical variables between bipolar (BP) (N = 44) and unipolar (UP) (N = 106) depression. BP depression (n = 44), mean values (SD) Mean age in years (SD) Mean age of onset of illness in years (SD) Females [n (%)] Bitemporal electrode placement (rest were bifrontal) [n (%)] Comorbid psychiatric diagnoses [n (%)] Melancholic symptoms [n (%)] Suicidal ideations [n (%)] Psychotic symptoms [n (%)] Mean duration of treatment before ECT in days (SD) Weight in kilograms (SD) Indications for ECT [n (%)] As a first line therapy To augment pharmacotherapy/medication resistant Clinical global impression – severity at the start of ECT sessions (SD) Thiopentone – mg (SD) Succinylcholine – mg (SD) Concurrent use of anti-epileptics [n (%)] P-value < 0.05 is considered statistically significant. t-independent samples t test.
32.6 (10.9) 24.3 (8.5) 24 (54.5) 40 (90.9) 9 (20.5) 24 (54.5) 25 (56.8) 29 (65.9) 4.2 (4.6) 57.1 (12.9) 32 (72.5) 12 (27.3) 5.4 (0.6) 172.3(39.3) 29.6 (6.8) 6 (13.6)
UP depression-(n = 106), mean values (SD)
t/chi-square
p
36.1 (13.5) 30.3 (13.2) 50 (47.2) 91 (86.7) 18 (17.0) 63 (59.4) 80 (75.5) 52 (49.1) 4.8 (4.9) 55.8 (14.1)
1.48 2.79 0.67 0.52 0.25 0.77 5.15 3.55 0.76 0.52
0.13 0.001 0.41 0.46 0.61 0.67 0.23 0.06 0.44 0.59
83 (78.3) 23 (27.1) 5.7 (0.6) 163.4 (42.0) 29.5 (8.0) 1 (1.0)
0.46
0.42
0.09 1.20 0.09 11.14
0.04 0.23 0.93 0.001
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Table 2 Comparison of ECT related and outcome variables between bipolar (BP) (N = 44) and unipolar (UP) (N = 106) depression. BP depression-(n = 44), mean values (SD) Clinical variables Number of ECTs Duration of inpatient stay after ECT initiation in days Improvement as per Likert scale
6.4 (2.4) 16.2 (9.1) 3.5 (1.1)
Seizure-related variables Threshold at first ECT in milli-coulombs Second threshold in milli-coulombs (n = 33 and 88 for BP and UP patients respectively) Third threshold in milli-coulombs (n = 12 and 27 for BP and UP patients respectively) Number of failed sessions to induce seizures Average duration of motor seizure in seconds
88.6 161.8 230.0 0.1 46.9
(75.1) (109.7) (84.2) (0.5) (14.0)
UP depression-(n = 106) mean values (SD) 6.5 (2.1) 16.6 (9.2) 4.0 (0.9)
83.2 152.0 258.8 0.1 46.7
(61.4) (80.3) (103.6) (0.3) (13.5)
t/chi-square/z
p
0.17 0.23 0.09
0.86 0.81 0.92
0.46 0.53 0.84 0.30 0.06
0.64 0.59 0.40 0.75 0.94
P value < 0.05 is considered statistically significant. z-Mann–Whitney U test; t-independent samples t test.
3. Results Table 1 shows the socio-demographic and clinical details of the study sample. BP depression group had the illness onset significantly earlier than UP depression group. However, there was no significant difference in the current age of patients in both these groups. Among the clinical characteristics, unipolar depression group had significantly higher occurrence of suicidality. The severity of illness according to the initial CGI measure was higher in UP depression group. The sample was comparable in other details like gender, electrode placement (bifrontal vs. bitemporal), presence of psychiatric comorbidities and other clinical characteristics. Similarly, groups were comparable in the indications for which ECT was initiated. The BP depression group had significantly higher use of anticonvulsants during the course of ECT. Table 2 shows the differences in the two groups in outcome variables. There was no significant difference between the groups in the number of ECTs received, seizure threshold at the first and subsequent sessions, number of failed attempts at seizure induction, the duration of hospital stay after initiation of ECTs and the improvement as per the likert scale. Multiple linear regression analysis was performed with the number of ECTs as dependent variable and the groups (BP depression and UP depression), age of onset and severity of illness as assessed by CGI as independent variables. The model was not significant (F = 0.99, p = 0.41). There were no major treatment emergent adverse effects noted. 4. Discussion The main purpose of the study was to elucidate whether there is a perceptible difference in efficacy of ECT between BP and UP depression groups. There was no difference between the groups in treatment efficacy with ECT in the present study as measured by the number of ECTs required, CGI severity at the end of treatment and the rating with Likert scale. Similarly, the groups did not show any difference based on failed ECT attempts and ECT days. Some of the earlier studies with a retrospective chart review design found that ECT had equivalent efficacy in BP and UP depressed patients (Abrams and Taylor, 1974; Avery and Winokur, 1977; Black et al., 1986). However, there are contrasting reports of higher efficacy in UP (Homan et al., 1982) and BP (Perris and d’Elia, 1966) groups. Recent studies conducted in a prospective manner have shown equal efficacy (Bailine et al., 2010; Daly et al., 2001; Sienaert et al., 2009) between groups. Daly and colleagues, using double-blind treatment protocol, examined the treatment efficacy with ECT between UP (n = 162) and BP depression (n = 66) (Daly et al., 2001). Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Patients with BP and
UP depression did not differ in rates of response or remission following the ECT course. However, in this study, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. In more recent double blind studies by Sienaert et al. (13 patients with BP and 51 patients with UP depression) and Bailine et al. (50 patients with BP and 170 patients with UP depression) ECT had equal efficacy (Bailine et al., 2010; Sienaert et al., 2009). However, both these studies reported a more rapid response in BP depression. In line with most observations, we found no difference between BP and UP patients in likelihood of response or degree of symptomatic improvement following the ECT course. ECT has been reported to be associated with provocation of a hypomanic or manic episode in BP depressed patients (Devanand et al., 1988). However, no patients in the present study developed a treatment emergent manic/hypomanic switch with ECT. Similarly, there were no serious untoward complications noted with ECT in either groups requiring treatment discontinuation. This being a chart-based study, the findings could have been biased by confounding factors. Age of onset of illness, concurrent use of anticonvulsants and severity of illness as measured by CGI severity were statistically different between the groups. Earlier age of onset in bipolar illness in documented earlier (Solomon et al., 2006). Since the severity of illness is higher in UP depression group, it could be argued that this could have leveled any possible efficacy favoring unipolar depression. Multiple linear regression analysis was done to control for these confounding factors and it was nonsignificant. Thus, these confounds may not explain the outcome. The absence of standardized methods of assessing the severity of illness (like standardized scales for assessing the severity) and adverse effects limits the interpretation of our study. However, number of ECTs administered to achieve clinically significant improvement and the number of hospital days form meaningful outcome measures – a previous study from our center has used similar measures (Hiremani et al., 2008). Examining the difference of efficacy in uncontrolled hospital setting coupled with inclusion of hospitalization indices would enable the results to be interpreted in the real world setting. Further, the fact that two raters who were blind to each others’ scores achieved a high reliability in their CGI and Likert scale scores partially validated this as a measure of meaningful clinical outcome. One more potential limitation is the absence of EEG seizure monitoring method in this study. The method using motor seizure parameters has been a useful and practical method in settings like ours where many patients receive ECT sessions daily. In that context, even though the ECT method of seizure monitoring appears superior, the motor seizure monitoring method appears more practical. Bipolar depression continues to be a condition with lesser response to the antidepressant medications, with a potential risk
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for switch to mania. There are many challenges in the treatment of BP depression where newer treatment strategies are being tried. ECT is efficacious and is not associated with any significant safety issues in BP depression which is similar to the use in UP depression. However, the present guidelines need to recognize the role of ECT in bipolar depression. Instead of reserving this option for refractory cases, it is prudent to consider it as an important clinical option wherever the resources are available. Conflict of interest None. References Abrams, R., Taylor, M.A., 1974. Unipolar and bipolar depressive illness: phenomenology and response to electroconvulsive therapy. Arch. Gen. Psychiatry 30, 320–321. APA, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Association, Washington, DC. APA, 2000. Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, 2nd ed. American Psychiatric Association, Washington, DC. APA, 2002. Treatment of Patients with Bipolar Disorder, 2nd ed. American Psychiatric Association, Washington, DC. Avery, D., Winokur, G., 1977. The efficacy of electroconvulsive therapy and antidepressants in depression. Biol. Psychiatry 12, 507–523. Bailine, S., Fink, M., Knapp, R., Petrides, G., Husain, M.M., Rasmussen, K., Sampson, S., Mueller, M., McClintock, S.M., Tobias, K.G., Kellner, C.H., 2010. Electroconvulsive therapy is equally effective in unipolar and bipolar depression. Acta Psychiatr. Scand. 121, 431–436. Black, D.W., Winokur, G., Nasrallah, A., 1986. ECT in unipolar and bipolar disorders: a naturalistic evaluation of 460 patients. Convuls. Ther. 2, 231–237. Chanpattana, W., Kunigiri, G., Kramer, B.A., Gangadhar, B.N., 2005. Survey of the practice of electroconvulsive therapy in teaching hospitals in India. J. ECT 21, 100–104.
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