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Influence of age on the efficacy of electroconvulsive therapy in major depression: A retrospective study
Journal of Affective Disorders 126 (2010) 257–261
Contents lists available at ScienceDirect
Journal of Affective Disorders j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j a d
Brief report
Influence of age on the efficacy of electroconvulsive therapy in major depression: A retrospective study Tom K. Birkenhäger a,⁎, Esther M. Pluijms a, Michel R. Ju a,c, Paul G. Mulder b, Walter W. van den Broek a a b c
Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands Department of Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands Department of Psychiatry, Amphia Hospital, Breda, The Netherlands
a r t i c l e
i n f o
Article history: Received 28 January 2010 Received in revised form 23 February 2010 Accepted 23 February 2010 Available online 19 March 2010
Keywords: Major depression Age ECT
a b s t r a c t Background: Several variables have been studied as possible predictors for the efficacy of ECT, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent. In older patients suffering from severe depression, ECT is often the treatment of choice, therefore, investigating the influence of age on ECT response is considered relevant. Method: At two depression units, 141 patients meeting DSM-IV criteria for major depression and scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were treated with bilateral ECT, twice weekly. Clinical evaluation of depressive symptoms was performed each week; scores on the HAM-D were obtained 1–3 days prior to ECT and 1–3 days after termination of the ECT course. The primary outcome criterion was defined a priori as the mean change on the HAM-D score. The influence of age on mean change on the HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode and presence of psychotic features. Results: Age as a continuous variable had no significant effect on the efficacy of ECT as measured by mean change on the HAM-D score (SE 0.057, p = 0.84). Limitations: The disproportionate distribution of patients among the three age groups appears to be the major limitation of the present study. Conclusion: This study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in younger depressed patients. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Electroconvulsive therapy (ECT) is a very effective treatment for major depressive disorder (Fink, 2001). The most convincing clinical predictors for response are the presence of delusions (Petrides et al., 2001; Birkenhäger et al., 2003) and psychomotor retardation (Hickie et al., 1996; Buchan et al., 1992). In older patients suffering from severe depression, ECT is often the treatment of choice due to the
⁎ Corresponding author. Department of Psychiatry, Erasmus MC, PO Box 2040, 3000CA Rotterdam, The Netherlands. Tel.: +31 10 7040139; fax: +31 10 4633217. E-mail address: [email protected] (T.K. Birkenhäger). 0165-0327/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2010.02.131
frequent presence of co-morbid medical illness, poor tolerance of antidepressants and malnutrition (Olfson et al., 1998). However, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent (Karlinsky and Shulman, 1984; Gormley et al., 1998; Tomac et al., 1997; Burke et al., 1987; Cattan et al., 1990). Most of these latter studies show several methodological flaws. Three later studies exploring the influence of age on response to ECT used better methodological standards. Wilkinson et al. (1993) found no significant relation between age and response to ECT, whereas O'Connor et al. (2001) and Tew et al. (1999) found an inferior response of younger patients with major depression to ECT. In these latter studies, however, analyses were not adjusted for the presence of
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T.K. Birkenhäger et al. / Journal of Affective Disorders 126 (2010) 257–261
psychotic features or the duration of the index episode as potential confounders. Moreover, the results of those studies may not be applicable to the population of depressed patients in the Netherlands where ECT is an ‘exceptional’ treatment administered almost exclusively to severely depressed inpatients.
determined by clinical observation. A minimum of 10 treatments was required before evaluation as a nonresponder. ECT was continued until patients were asymptomatic or had shown no further improvement over 3 consecutive treatments. 2.3. Evaluation of treatment outcome
1.1. Aim of the study
2. Methods
The 17-item HAM-D was routinely performed 1–3 days prior to ECT, weekly during the course of ECT, and 1–3 days after treatment termination. Response was defined as a reduction of at least 50% on the 17-item HAM-D. A continuous response score (primary outcome criterion) was defined as the change in HAM-D score. Remission was defined as a score ≥7 after the final ECT treatment. Side-effects were not systematically assessed; however any serious side-effects were documented.
2.1. Subjects
2.4. Statistical analysis
We reviewed the records of 186 inpatients who met the DSM-IV criteria (American Psychiatric Association, 1994) for major depression. Diagnoses were based on clinical observation during a drug-free period. A diagnosis of psychotic depression was made only when the patient showed definite mood-congruent delusions. Consecutive patients were treated with ECT during a six-year period at the depression units of Parnassia Psychomedical Center (PPC) in The Hague and the Erasmus Medical Center (EMC) in Rotterdam. Both departments are reserved for severely depressed inpatients. Patients were included if they met the DSM-IV criteria for major depressive disorder and had a score of ≥18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) (Hamilton, 1960). Exclusion criteria were: a prior course of ECT, a lifetime history of schizophrenia, bipolar or schizoaffective disorder and the presence of neurologic or serious medical illness. We restricted our sample to patients treated with bilateral ECT, to avoid electrode placement acting as additional possible confounding factor.
All statistical analyses were performed on an intention-totreat principle; for patients who dropped out, the score of the last week with treatment was carried forward. Dichotomous clinical variables were compared between groups using the χ2 test. The t-test and F-test were used to compare continuous variables with a Gaussian-shaped distribution between two, or more than two groups, respectively. For variables with a non-symmetric distribution the respective Mann–Whitney and Kruskal–Wallis tests were used. The primary outcome criterion was defined a priori as the mean change in HAM-D score. The influence of age on the mean change in HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode, and presence of psychotic features. The influence of age on the attainment of remission was analyzed with logistic regression, adjusted for the same set of covariables. Statistical significance was defined as p b 0.05. Statistical analyses were performed using SPSS for Windows, version 16.0 (SPSS Inc., Chicago, Ill, USA).
The present study examined the influence of age on the efficacy of ECT in a homogeneous population of drug-free inpatients with severe major depression. Since ECT is often the treatment of choice for elderly depressed inpatients, assessing its efficacy compared with that in younger age groups is considered relevant.
2.2. Electroconvulsive therapy 3. Results Patients were withdrawn from all psychotropic medication one week before ECT and were maintained medicationfree during the course of ECT; in case of severe agitation incidental use of haloperidol was allowed. All patients were treated with bilateral ECT, administered twice weekly with a brief-pulse, constant current apparatus (Thymatron, Somatics, IL, USA). Anaesthesia was induced with thiopental (1.0–2.5 mg/kg) (PPC) or etomidate (0.2– 0.3 mg/kg) (EMC) and succinylcholine (0.5–1.0 mg/kg) after premedication with an anticholinergic agent (0.5 mg atropine (PPC) or 0.2 mg glycopyrrolate (EMC). At PPC the half-age method (Petrides and Fink, 1996) was used to determine stimulus dose, and at EMC a dose-titration method (Sackeim et al., 1987) was used to determine seizure threshold. Stimulus dosage was set at 1.5 times seizure threshold. Motor and EEG seizure duration were monitored. During the course of ECT stimulus dosage was adjusted upwards to maintain seizure duration of at least 25 s as measured with the cuff method. The number of ECT treatments was
3.1. Patient characteristics The total study sample consisted of 141 inpatients (105 women and 36 men) with a mean age of 55.6 (range: 20–86) (Fig. 1). In total 75 patients suffered from psychotic depression and 66 from depression without psychotic features. Table 1 gives the demographic and clinical characteristics for the total sample, and separately for three age groups 18–45, 46–64 and 65–86 years. The average number of ECT sessions received was 13.5 for the total sample, with a similar number for each of the age groups. 3.2. Effect of age on the efficacy of ECT Age as a continuous variable had no significant effect on the efficacy of ECT as measured by the mean change in HAM-D score, adjusted for the potential confounding factors (center, duration of index episode and presence of psychotic features)
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259
Table 1 Demographic and clinical characteristics for the total sample, and separately for the three age groups. Variable
Total sample (n = 141)
18–45 years (n = 33)
46–64 years (n = 76)
65–85 years (n = 32)
Age, years Gender, % women
55.6 ± 13.3 74.5% (105/141) 53.2% (75) 82.9% (117) 16.5 ± 16.7 13.5 ± 5.6
38.5 ± 5.9 72.7% (24/33) 36.4 % (12) 72.7% (24) 19.1 ± 20.4 13.6 ± 4.0
55.2 ± 5.4 73.7% (56/76) 55.3% (42) 84.2% (64) 18.7 ± 17.0 13.9 ± 5.4
74.0 ± 6.0 78.1% (25/32) 65.6% (21) 90.6% (29) 8.5 ± 6.8 12.0 ± 7.2
Psychotic features, %, (n) Melancholic features, %, n Length of the index episode, mo Number of ECTs
p-value
0.67 a 0.05 a 0.28 b 0.008 b 0.47 b
Data are presented as mean ± standard deviation, unless otherwise indicated. a Analysed with the χ2 test. b Analysed with the t-test.
(SE 0.057, p = 0.84). The same analysis without adjustment for psychotic features also showed no significant effect of age on the mean change on the HAM-D score (SE = 0.060, p = 0.28). For the secondary outcome criterion, remission, age also had no significant effect on the attainment of remission, adjusted for the same set of covariables (Table 2). Six patients (1.5%) terminated the ECT course prematurely, all refused further ECT sessions.
3.3. Effect of presence of psychotic features on outcome Baseline illness severity, as measured with the 17-item HAM-D total score, was significantly higher for patients with psychotic depression compared with nonpsychotic patients: 31.8 ± 6.58 points versus 25.3 ± 6.30 points, p b 0.005. The efficacy of ECT was significantly superior in patients with psychotic depression: the mean change in the HAM-D score is − 21.8 ± 8.71 points versus − 14.4 ± 7.63 points in the sample without psychotic features, p b 0.005. The proportion of patients attaining full remission showed no significant difference: 31 of 75 (41.3%) versus 24 of 66 (36.4 %) patients, χ2 = 3.64, p = 0.55. Response was achieved by 64 of 75 (85.3%) patients with
Fig. 1. Absolute frequency distribution of age.
psychotic depression versus 45 of 66 (68.2%) nonpsychotic patients, χ2 = 5.89, p = 0.015. 4. Discussion In contrast to our expectation, in the present study age appears to have no effect on the efficacy of a course of ECT in a sample of major depressive inpatients, either with or without adjustment for psychotic features as a covariable. ECT appeared to be efficacious in all three age groups. The younger sample (18–45 years) showed the lowest rates of response and remission, but not at the level of significance. The proportion of patients suffering from psychotic depression appeared to increase with age, which is in accordance with previous studies. Response to ECT was significantly superior in patients with psychotic depression. 4.1. Comparison with previous reports: presence of psychotic and melancholic features The apparent lack of influence of age on the efficacy of ECT is in contrast to the results of several earlier studies. Wilkinson et al. (1993) found a 54% response rate in younger patients (18–64 years) and a 73% response rate in older patients (65–88 years); a non-significant difference. The proportion of patients with psychotic features in each age group were similar. Tew et al. (1999) compared the response to ECT in three age groups and found a superior response to ECT in older patients. The response rate for patients aged 60– 74 years (73%) and 75 years and older (67%) was not different, patients under 60 years showed a significantly lower response rate (54%). O'Connor et al. (2001) also found a superior response to ECT in older patients. Older patients in the study of Tew et al. (1999) had significantly shorter duration of index episode, were less likely to be medication resistant, were more likely to have received ECT in the past, and were more likely to have melancholic features. In the study of O'Connor et al. (2001) elderly patients had significantly less previous depressive episodes and were more likely to have psychotic features. In neither of these studies statistical analyses were adjusted for these potential confounders. O'Connor et al. (2001) noted that the observed superior response of middle-aged and elderly patients in their study may be caused by the higher percentage of patients with psychotic depression in the middle-aged and elderly
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Table 2 Treatment effect based on the outcome criteria across the three age groups. Outcome
Total sample
18–45 years
46–64 years
65–85 years
p
Response (HAM-D↓ ≥50%) Remission (HAM-D ≤ 7) Baseline HAM-D (mean) Post-ECT HAM-D (mean) HAM-D change
77.3% (109/141) 41.8% (59/141) 28.8 ± 7.2 10.5 ± 6.6 18.3 ± 9.0
69.7% (23/33) 33.3% (11/33) 28.1 ± 6.6 10.5 ± 5.0 17.6 ± 8.4
81.6% (62/76) 44.7% (34/76) 28.7 ± 6.8 10.2 ± 6.6 18.6 ± 8.7
75.0% (24/32) 43.8% (14/32) 29.7 ± 8.6 11.3 ± 8.1 18.4 ± 10.4
0.37 a
a b
0.63 a 0.61 b 0.68 b 0.55 b
Analysed with the χ2 test. Analysed with the t-test.
groups. The same confounding factor may account for the results reported by Tew et al. (1999). With regard to patient selection there are very few differences between our study and that of O'Connor et al. (2001) and Tew et al. (1999); however, the baseline severity is difficult to compare, since we used the 17-item HAM-D, instead of the 24-item version. The most probable explanation for our failure to find an effect of age on the efficacy of ECT is the small number of patients in the younger (18–45 years) sample. Therefore, if the efficacy of ECT is less in young patients with major depression as compared with middle-aged and elderly patients (as suggested by O'Connor et al. (2001) and Tew et al. (1999)), such an effect may have been missed in our study because of the small number of patients in that specific subgroup. 4.2. Comparison with previous reports: the administration of ECT Differences in the administration of ECT might also explain the conflicting results. Wilkinson et al. (1993) provide no information on electrode placement or the use of concomitant medication during ECT. In the study of Tew et al. (1999) concomitant use of lorazepam was allowed and a proportion of patients received right unilateral ECT with a stimulus dose of at least 150% above seizure threshold, which is nowadays considered a less effective form of ECT (Fink and Taylor, 2007). Patients in the study of O'Connor et al. (2001) were treated with bilateral ECT and concomitant use of lorazepam and diphenhydramine was allowed. The incidental use of haloperidol is a confounding factor in our study. Furthermore, the number of ECT treatments was substantially higher in our study compared with O' Connor's study and the study by Tew. However, in contrast to others, we found no evidence for an inferior efficacy of ECT in elderly depressed patients: in our study ECT appeared to be effective in patients aged over 65 years. 4.3. Study limitations There are some limitations to the present study. The two centers used a different dosing strategy for ECT and different anaesthesia. Furthermore, the side-effects of ECT were not systematically assessed. Diagnoses were made without a diagnostic interview. Finally, the disproportionate distribution of patients among the three age groups is probably the most important limitation of this study. In conclusion, this study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in
younger depressed patients. ECT was well tolerated in all patients. Role of the funding source No external funding.
Conflict of interest TKB and WWvdB have received grants from Wyeth pharmaceuticals. TKB has received speakers' fees from Wyeth pharmaceuticals, Servier and Astra Zeneca. WWvdB has received speakers' fees from Wyeth pharmaceuticals and Servier. EMP, MRJ and PGM have no conflict of interest.
Acknowledgements We thank Mrs. S. Verploegh who assisted with the data collection and Mrs. L. Visser-Isles for English language editing. References American Psychiatric Association, 1994. Diagnostic and Statistical manual of Mental disorders, 4th edition. American Psychiatric Association, Washington, DC. Birkenhäger, T.K., Pluijms, E.M., Lucius, S.A., 2003. ECT response in delusional versus non-delusional depressed inpatients. J. Affect. Disord. 74, 191–195. Buchan, H., Johnstone, E.C., McPherson, K., Palmer, R.L., Crow, T.J., Brandon, S., 1992. Who benefits from electroconvulsive therapy? Combined results of the Leicester and Northwick Park trials. Br. J. Psychiatry 160 (3), 55–359. Burke, W.J., Rubin, E.H., Zorumski, C.F., Wetzel, R.D., 1987. The safety of ECT in geriatric psychiatry. J. Am. Geriatr. Soc. 35, 516–521. Cattan, R.A., Berry, P.P., Mead, G., Reefe, W.E., Gay, A., Silverman, M., 1990. Electroconvulsive therapy in octogenarians. J. Am. Geriatr. Soc. 38, 753–758. Fink, M., 2001. Convulsive therapy: a review of the first 55 years. J. Affect. Disord. 63, 1–15. Fink, M., Taylor, M.A., 2007. Electroconvulsive therapy: evidence and challenges. JAMA 298, 330–332. Gormley, N., Cullen, C., Walters, L., Philpot, M., Lawlor, B., 1998. The safety and efficacy of electroconvulsive therapy in patients over age 75. Int. J. Geriatr. Psychiatry 13, 871–874. Hamilton, M., 1960. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 23, 56–62. Hickie, I., Mason, C., Parker, G., Brodaty, H., 1996. Prediction of ECT response: validation of a refined sign-based (CORE) system for defining melancholia. Br. J. Psychiatry 169, 68–74. Karlinsky, H., Shulman, K.I., 1984. The clinical use of electroconvulsive therapy in old age. J. Am. Geriatr. Soc. 32, 183–186. O' Connor, M.K., Knapp, R., Husain, M., Rummans, T.A., Petrides, G., Smith, G., Mueller, M., Snyder, K., Bernstein, H., Rush, A.J., Fink, M., Kellner, C., 2001. The influence of age on the response of major depression to electroconvulsive therapy. A CORE report. Am. J. Geriatr. Psychiatry 9, 382–390. Olfson, M., Marcus, M., Sackeim, H.A., Thompson, J., Pincus, H.A., 1998. Use of ECT for the inpatient treatment of recurrent major depression. Am. J. Psychiatry 155, 22–29.
T.K. Birkenhäger et al. / Journal of Affective Disorders 126 (2010) 257–261 Petrides, G., Fink, M., 1996. The ‘half-age’ stimulation strategy for ECT dosing. J. ECT 12, 138–146. Petrides, G., Fink, M., Husain, M.M., Knapp, R.G., Rush, A.J., Mueller, M., Rummans, T.A., O'Connor, M.K., Rasmussen, K.G., Bernstein, H.J., Biggs, M., Bailine, S.H., Kellner, C.H., 2001. ECT remission rates in psychotic versus nonpsychotic depressed patients: a report from CORE. J. ECT 17, 244–253. Sackeim, H.A., Decina, P., Kanzler, M., Kerr, B., Malitz, S., 1987. Effects of electrode placement on the efficacy of titrated, low-dose ECT. Am. J. Psychiatry 144, 1449–1455.
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Tew, J.D., Mulsant, B.H., Haskett, R.F., Dolata, D., Hixson, L., Mann, J.J., 1999. Acute efficacy of ECT in the treatment of major depression in the old-old. Am. J. Psychiatry 156, 1865–1870. Tomac, T.A., Rummans, T.A., Pileggi, T.S., 1997. Safety and efficacy of electroconvulsive therapy in patients over age 85. Am. J. Geriatr. Psychiatry 5, 126–130. Wilkinson, A.M., Anderson, D.N., Peters, S., 1993. Age and the effects of ECT. Int. J. Geriatr. Psychiatry 8, 401–406.
Contents lists available at ScienceDirect
Journal of Affective Disorders j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j a d
Brief report
Influence of age on the efficacy of electroconvulsive therapy in major depression: A retrospective study Tom K. Birkenhäger a,⁎, Esther M. Pluijms a, Michel R. Ju a,c, Paul G. Mulder b, Walter W. van den Broek a a b c
Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands Department of Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands Department of Psychiatry, Amphia Hospital, Breda, The Netherlands
a r t i c l e
i n f o
Article history: Received 28 January 2010 Received in revised form 23 February 2010 Accepted 23 February 2010 Available online 19 March 2010
Keywords: Major depression Age ECT
a b s t r a c t Background: Several variables have been studied as possible predictors for the efficacy of ECT, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent. In older patients suffering from severe depression, ECT is often the treatment of choice, therefore, investigating the influence of age on ECT response is considered relevant. Method: At two depression units, 141 patients meeting DSM-IV criteria for major depression and scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were treated with bilateral ECT, twice weekly. Clinical evaluation of depressive symptoms was performed each week; scores on the HAM-D were obtained 1–3 days prior to ECT and 1–3 days after termination of the ECT course. The primary outcome criterion was defined a priori as the mean change on the HAM-D score. The influence of age on mean change on the HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode and presence of psychotic features. Results: Age as a continuous variable had no significant effect on the efficacy of ECT as measured by mean change on the HAM-D score (SE 0.057, p = 0.84). Limitations: The disproportionate distribution of patients among the three age groups appears to be the major limitation of the present study. Conclusion: This study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in younger depressed patients. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Electroconvulsive therapy (ECT) is a very effective treatment for major depressive disorder (Fink, 2001). The most convincing clinical predictors for response are the presence of delusions (Petrides et al., 2001; Birkenhäger et al., 2003) and psychomotor retardation (Hickie et al., 1996; Buchan et al., 1992). In older patients suffering from severe depression, ECT is often the treatment of choice due to the
⁎ Corresponding author. Department of Psychiatry, Erasmus MC, PO Box 2040, 3000CA Rotterdam, The Netherlands. Tel.: +31 10 7040139; fax: +31 10 4633217. E-mail address: [email protected] (T.K. Birkenhäger). 0165-0327/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2010.02.131
frequent presence of co-morbid medical illness, poor tolerance of antidepressants and malnutrition (Olfson et al., 1998). However, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent (Karlinsky and Shulman, 1984; Gormley et al., 1998; Tomac et al., 1997; Burke et al., 1987; Cattan et al., 1990). Most of these latter studies show several methodological flaws. Three later studies exploring the influence of age on response to ECT used better methodological standards. Wilkinson et al. (1993) found no significant relation between age and response to ECT, whereas O'Connor et al. (2001) and Tew et al. (1999) found an inferior response of younger patients with major depression to ECT. In these latter studies, however, analyses were not adjusted for the presence of
258
T.K. Birkenhäger et al. / Journal of Affective Disorders 126 (2010) 257–261
psychotic features or the duration of the index episode as potential confounders. Moreover, the results of those studies may not be applicable to the population of depressed patients in the Netherlands where ECT is an ‘exceptional’ treatment administered almost exclusively to severely depressed inpatients.
determined by clinical observation. A minimum of 10 treatments was required before evaluation as a nonresponder. ECT was continued until patients were asymptomatic or had shown no further improvement over 3 consecutive treatments. 2.3. Evaluation of treatment outcome
1.1. Aim of the study
2. Methods
The 17-item HAM-D was routinely performed 1–3 days prior to ECT, weekly during the course of ECT, and 1–3 days after treatment termination. Response was defined as a reduction of at least 50% on the 17-item HAM-D. A continuous response score (primary outcome criterion) was defined as the change in HAM-D score. Remission was defined as a score ≥7 after the final ECT treatment. Side-effects were not systematically assessed; however any serious side-effects were documented.
2.1. Subjects
2.4. Statistical analysis
We reviewed the records of 186 inpatients who met the DSM-IV criteria (American Psychiatric Association, 1994) for major depression. Diagnoses were based on clinical observation during a drug-free period. A diagnosis of psychotic depression was made only when the patient showed definite mood-congruent delusions. Consecutive patients were treated with ECT during a six-year period at the depression units of Parnassia Psychomedical Center (PPC) in The Hague and the Erasmus Medical Center (EMC) in Rotterdam. Both departments are reserved for severely depressed inpatients. Patients were included if they met the DSM-IV criteria for major depressive disorder and had a score of ≥18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) (Hamilton, 1960). Exclusion criteria were: a prior course of ECT, a lifetime history of schizophrenia, bipolar or schizoaffective disorder and the presence of neurologic or serious medical illness. We restricted our sample to patients treated with bilateral ECT, to avoid electrode placement acting as additional possible confounding factor.
All statistical analyses were performed on an intention-totreat principle; for patients who dropped out, the score of the last week with treatment was carried forward. Dichotomous clinical variables were compared between groups using the χ2 test. The t-test and F-test were used to compare continuous variables with a Gaussian-shaped distribution between two, or more than two groups, respectively. For variables with a non-symmetric distribution the respective Mann–Whitney and Kruskal–Wallis tests were used. The primary outcome criterion was defined a priori as the mean change in HAM-D score. The influence of age on the mean change in HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode, and presence of psychotic features. The influence of age on the attainment of remission was analyzed with logistic regression, adjusted for the same set of covariables. Statistical significance was defined as p b 0.05. Statistical analyses were performed using SPSS for Windows, version 16.0 (SPSS Inc., Chicago, Ill, USA).
The present study examined the influence of age on the efficacy of ECT in a homogeneous population of drug-free inpatients with severe major depression. Since ECT is often the treatment of choice for elderly depressed inpatients, assessing its efficacy compared with that in younger age groups is considered relevant.
2.2. Electroconvulsive therapy 3. Results Patients were withdrawn from all psychotropic medication one week before ECT and were maintained medicationfree during the course of ECT; in case of severe agitation incidental use of haloperidol was allowed. All patients were treated with bilateral ECT, administered twice weekly with a brief-pulse, constant current apparatus (Thymatron, Somatics, IL, USA). Anaesthesia was induced with thiopental (1.0–2.5 mg/kg) (PPC) or etomidate (0.2– 0.3 mg/kg) (EMC) and succinylcholine (0.5–1.0 mg/kg) after premedication with an anticholinergic agent (0.5 mg atropine (PPC) or 0.2 mg glycopyrrolate (EMC). At PPC the half-age method (Petrides and Fink, 1996) was used to determine stimulus dose, and at EMC a dose-titration method (Sackeim et al., 1987) was used to determine seizure threshold. Stimulus dosage was set at 1.5 times seizure threshold. Motor and EEG seizure duration were monitored. During the course of ECT stimulus dosage was adjusted upwards to maintain seizure duration of at least 25 s as measured with the cuff method. The number of ECT treatments was
3.1. Patient characteristics The total study sample consisted of 141 inpatients (105 women and 36 men) with a mean age of 55.6 (range: 20–86) (Fig. 1). In total 75 patients suffered from psychotic depression and 66 from depression without psychotic features. Table 1 gives the demographic and clinical characteristics for the total sample, and separately for three age groups 18–45, 46–64 and 65–86 years. The average number of ECT sessions received was 13.5 for the total sample, with a similar number for each of the age groups. 3.2. Effect of age on the efficacy of ECT Age as a continuous variable had no significant effect on the efficacy of ECT as measured by the mean change in HAM-D score, adjusted for the potential confounding factors (center, duration of index episode and presence of psychotic features)
T.K. Birkenhäger et al. / Journal of Affective Disorders 126 (2010) 257–261
259
Table 1 Demographic and clinical characteristics for the total sample, and separately for the three age groups. Variable
Total sample (n = 141)
18–45 years (n = 33)
46–64 years (n = 76)
65–85 years (n = 32)
Age, years Gender, % women
55.6 ± 13.3 74.5% (105/141) 53.2% (75) 82.9% (117) 16.5 ± 16.7 13.5 ± 5.6
38.5 ± 5.9 72.7% (24/33) 36.4 % (12) 72.7% (24) 19.1 ± 20.4 13.6 ± 4.0
55.2 ± 5.4 73.7% (56/76) 55.3% (42) 84.2% (64) 18.7 ± 17.0 13.9 ± 5.4
74.0 ± 6.0 78.1% (25/32) 65.6% (21) 90.6% (29) 8.5 ± 6.8 12.0 ± 7.2
Psychotic features, %, (n) Melancholic features, %, n Length of the index episode, mo Number of ECTs
p-value
0.67 a 0.05 a 0.28 b 0.008 b 0.47 b
Data are presented as mean ± standard deviation, unless otherwise indicated. a Analysed with the χ2 test. b Analysed with the t-test.
(SE 0.057, p = 0.84). The same analysis without adjustment for psychotic features also showed no significant effect of age on the mean change on the HAM-D score (SE = 0.060, p = 0.28). For the secondary outcome criterion, remission, age also had no significant effect on the attainment of remission, adjusted for the same set of covariables (Table 2). Six patients (1.5%) terminated the ECT course prematurely, all refused further ECT sessions.
3.3. Effect of presence of psychotic features on outcome Baseline illness severity, as measured with the 17-item HAM-D total score, was significantly higher for patients with psychotic depression compared with nonpsychotic patients: 31.8 ± 6.58 points versus 25.3 ± 6.30 points, p b 0.005. The efficacy of ECT was significantly superior in patients with psychotic depression: the mean change in the HAM-D score is − 21.8 ± 8.71 points versus − 14.4 ± 7.63 points in the sample without psychotic features, p b 0.005. The proportion of patients attaining full remission showed no significant difference: 31 of 75 (41.3%) versus 24 of 66 (36.4 %) patients, χ2 = 3.64, p = 0.55. Response was achieved by 64 of 75 (85.3%) patients with
Fig. 1. Absolute frequency distribution of age.
psychotic depression versus 45 of 66 (68.2%) nonpsychotic patients, χ2 = 5.89, p = 0.015. 4. Discussion In contrast to our expectation, in the present study age appears to have no effect on the efficacy of a course of ECT in a sample of major depressive inpatients, either with or without adjustment for psychotic features as a covariable. ECT appeared to be efficacious in all three age groups. The younger sample (18–45 years) showed the lowest rates of response and remission, but not at the level of significance. The proportion of patients suffering from psychotic depression appeared to increase with age, which is in accordance with previous studies. Response to ECT was significantly superior in patients with psychotic depression. 4.1. Comparison with previous reports: presence of psychotic and melancholic features The apparent lack of influence of age on the efficacy of ECT is in contrast to the results of several earlier studies. Wilkinson et al. (1993) found a 54% response rate in younger patients (18–64 years) and a 73% response rate in older patients (65–88 years); a non-significant difference. The proportion of patients with psychotic features in each age group were similar. Tew et al. (1999) compared the response to ECT in three age groups and found a superior response to ECT in older patients. The response rate for patients aged 60– 74 years (73%) and 75 years and older (67%) was not different, patients under 60 years showed a significantly lower response rate (54%). O'Connor et al. (2001) also found a superior response to ECT in older patients. Older patients in the study of Tew et al. (1999) had significantly shorter duration of index episode, were less likely to be medication resistant, were more likely to have received ECT in the past, and were more likely to have melancholic features. In the study of O'Connor et al. (2001) elderly patients had significantly less previous depressive episodes and were more likely to have psychotic features. In neither of these studies statistical analyses were adjusted for these potential confounders. O'Connor et al. (2001) noted that the observed superior response of middle-aged and elderly patients in their study may be caused by the higher percentage of patients with psychotic depression in the middle-aged and elderly
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Table 2 Treatment effect based on the outcome criteria across the three age groups. Outcome
Total sample
18–45 years
46–64 years
65–85 years
p
Response (HAM-D↓ ≥50%) Remission (HAM-D ≤ 7) Baseline HAM-D (mean) Post-ECT HAM-D (mean) HAM-D change
77.3% (109/141) 41.8% (59/141) 28.8 ± 7.2 10.5 ± 6.6 18.3 ± 9.0
69.7% (23/33) 33.3% (11/33) 28.1 ± 6.6 10.5 ± 5.0 17.6 ± 8.4
81.6% (62/76) 44.7% (34/76) 28.7 ± 6.8 10.2 ± 6.6 18.6 ± 8.7
75.0% (24/32) 43.8% (14/32) 29.7 ± 8.6 11.3 ± 8.1 18.4 ± 10.4
0.37 a
a b
0.63 a 0.61 b 0.68 b 0.55 b
Analysed with the χ2 test. Analysed with the t-test.
groups. The same confounding factor may account for the results reported by Tew et al. (1999). With regard to patient selection there are very few differences between our study and that of O'Connor et al. (2001) and Tew et al. (1999); however, the baseline severity is difficult to compare, since we used the 17-item HAM-D, instead of the 24-item version. The most probable explanation for our failure to find an effect of age on the efficacy of ECT is the small number of patients in the younger (18–45 years) sample. Therefore, if the efficacy of ECT is less in young patients with major depression as compared with middle-aged and elderly patients (as suggested by O'Connor et al. (2001) and Tew et al. (1999)), such an effect may have been missed in our study because of the small number of patients in that specific subgroup. 4.2. Comparison with previous reports: the administration of ECT Differences in the administration of ECT might also explain the conflicting results. Wilkinson et al. (1993) provide no information on electrode placement or the use of concomitant medication during ECT. In the study of Tew et al. (1999) concomitant use of lorazepam was allowed and a proportion of patients received right unilateral ECT with a stimulus dose of at least 150% above seizure threshold, which is nowadays considered a less effective form of ECT (Fink and Taylor, 2007). Patients in the study of O'Connor et al. (2001) were treated with bilateral ECT and concomitant use of lorazepam and diphenhydramine was allowed. The incidental use of haloperidol is a confounding factor in our study. Furthermore, the number of ECT treatments was substantially higher in our study compared with O' Connor's study and the study by Tew. However, in contrast to others, we found no evidence for an inferior efficacy of ECT in elderly depressed patients: in our study ECT appeared to be effective in patients aged over 65 years. 4.3. Study limitations There are some limitations to the present study. The two centers used a different dosing strategy for ECT and different anaesthesia. Furthermore, the side-effects of ECT were not systematically assessed. Diagnoses were made without a diagnostic interview. Finally, the disproportionate distribution of patients among the three age groups is probably the most important limitation of this study. In conclusion, this study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in
younger depressed patients. ECT was well tolerated in all patients. Role of the funding source No external funding.
Conflict of interest TKB and WWvdB have received grants from Wyeth pharmaceuticals. TKB has received speakers' fees from Wyeth pharmaceuticals, Servier and Astra Zeneca. WWvdB has received speakers' fees from Wyeth pharmaceuticals and Servier. EMP, MRJ and PGM have no conflict of interest.
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