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Efficacy and Safety of Continuation and Maintenance Electroconvulsive Therapy in Depressed Elderly Patients: A Systematic Review
CRITICAL REVIEW ARTICLE
Efficacy and Safety of Continuation and Maintenance Electroconvulsive Therapy in Depressed Elderly Patients: A Systematic Review Audrey M. van Schaik, M.D., Hannie C. Comijs, Ph.D., Caroline M. Sonnenberg, M.D., Aartjan T. Beekman, M.D., Ph.D., Pascal Sienaert, M.D., Ph.D., Max L. Stek, M.D., Ph.D.
Background: Electroconvulsive therapy (ECT) is the most efficacious treatment in severely depressed elderly patients. Relapse and recurrence of geriatric depression after recovery is an important clinical issue, which requires vigorous and safe treatment in the long term. Continuation or maintenance ECT (M-ECT) may play an important role in this respect. Methods: In this systematic search, we evaluate the efficacy and safety of M-ECT in preventing depressive relapse in patients age 55 or older. Computer databases were searched for relevant literature published from 1966 until August 2010 with additional references. Results: Twenty-two studies met the search criteria including three randomized clinical trials. M-ECT was studied in nine studies exclusively in the elderly patients. Conclusions: Research on this clinically important topic is sparse. On the basis of available literature, M-ECT is probably as effective as continuation medication in severely depressed elderly patients after a successful course of ECT and is generally well tolerated. To date, methodologically sound studies, which take into account important issues in geriatric depression like cognition, comorbidity, and clinical parameters, are lacking. (Am J Geriatr Psychiatry 2012; 20:5–17) Key Words: Continuation, depressive disorder, ECT, elderly, electroconvulsive therapy, geriatric, maintenance, major depression, review
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lectroconvulsive therapy (ECT) is an effective and safe treatment for severe depression.1,2 In depressed elderly patients, ECT may have an even higher immediate response rate than in younger patients.3,4 After successful treatment with ECT, the
prevention of relapse and recurrence of a new depressive episode is very important. Without pharmacotherapy, 85% of the patients relapse in the first 6 months after successful ECT and even with medication relapse rates are approximately 50%.5
Received April 7, 2010; revised November 4, 2010; accepted November 7, 2010. From the GGZ inGeest/VU University Medical Center, Amsterdam, the Netherlands (AMvS, HCC, CMS, ATB, MLS); and University Psychiatric Center, Catholic University of Leuven, Campus Kortenberg, Belgium (PS). No sources of support. Send correspondence and reprint requests to Audrey M. van Schaik, M.D., GGZ inGeest, Valeriusplein 14, 1075 BH Amsterdam, the Netherlands. e-mail: [email protected] c 2011 American Association for Geriatric Psychiatry DOI: 10.1097/JGP.0b013e31820dcbf9
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Electroconvulsive Therapy in Depressed Elderly Patients Consequently, all patients successfully treated with ECT nowadays use antidepressants or get maintenance or continuation ECT, afterwards, or both to reduce this risk. Continuation ECT is defined as treatment over 6 months after the remission of an index episode of depression to prevent relapse. Electroconvulsive therapy after this 6-month period has been called maintenance ECT and does not have a fixed end point.6 In this review, the term maintenance ECT (M-ECT) will be used referring to both continuation and maintenance ECT. Depressed elderly patients are treated with acute ECT more often than younger adults for several reasons.7 First, they often have poor tolerance to pharmacotherapy in the presence of comorbid physical problems, such as cardiovascular disease, and the related frequent use of multiple drugs. Second, severe depression leads more often to life-threatening conditions in frail elderly patients requiring a fast treatment response.8 Generally, elderly patients are more at risk for relapse of depression after successful treatment, which may be caused by medical comorbidity and a higher likelihood of previous depression in the elderly patients.8 Furthermore, the high frequency of treatment-resistant depression and psychotic depression in old age contributes to higher relapse rates after ECT.9–11 Consequently, elderly patients are probably more referred to M-ECT. Although M-ECT needs repetitive anesthesia, it is difficult to organize in many places, is expensive, and can be burdensome especially for frail elderly patients and their relatives. In daily practice, choices for relapse preventing treatment should be based on clinical experience and research. To date, no systematic review was done on the efficacy and safety of M-ECT in the prevention of relapse or recurrence of depressive episodes in the elderly patients. Previous reviews on M-ECT included studies in all age groups or a broader range of psychiatric disorders, such as bipolar disorder and schizophrenia.12–20 The objective of this study is to review the research on the efficacy and safety of M-ECT in depressed elderly patients.
METHODS Selection of articles involved three steps. First, the computer databases MEDLINE, Cochrane, Embase, and Psychinfo were searched for published studies in the period from 1966 to August 2010. “Mainte-
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nance electroconvulsive therapy” or “continuation electroconvulsive therapy” or “maintenance ECT” or “continuation ECT” in combination with “depressive disorder” or “major depression” were used as key words. Second, relevant articles (based on title and abstract) were screened manually and their bibliographies were searched for additional references to identify studies on M-ECT. Third, all retrieved articles were screened to meet the following inclusion criteria: 1. Studies on maintenance or continuation ECT as intervention to prevent relapse or recurrence of depression. 2. Studies on M-ECT in affective disorders with at least 50% of the patients diagnosed with unipolar depression. 3. Subjects’ mean age 55 years or more. 4. A minimum of 5 patients with unipolar depression in the study group or case series. 5. Evaluation of the efficacy of M-ECT. Randomized clinical trails (RCTs) and prospective and retrospective cohort studies were included for the review. The first author (AMvS) and one of the coauthors (MLS) read the abstracts to determine their relevance to the review. In the next step, the manuscript was screened to examine whether criteria for age, minimum number of patients, and the presence of standardized evaluation were met. No selection in language was made. If there was insufficient information in the study with regard to one or more of the criteria, we tried to contact the authors for additional information.
RESULTS The data search by key words yielded 125 potentially relevant articles. Additional 21 studies were found by cross-referencing. In Figure 1, we show the flow diagram of the selection of the studies for this review. A total of 124 studies were excluded resulting in 22 studies meeting all the selection criteria. From these studies, 9 studies included exclusively patients older than 55 years. The other 13 studies included adult patients (age range, 18–94), but with a mean age of 55 years or older. This procedure identified 3 RCTs, 5 prospective cohort studies, 3 retrospective cohort studies with a matched comparison group, and 11 retrospective cohort studies (Table 1).
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van Schaik et al.
FIGURE 1.
Flow diagram of selection of studies.
EFFICACY OF M-ECT Randomized Clinical Trials Three RCTs with a different methodology were found, one large multicenter trial in all age categories of Kellner and colleagues21 and two smaller studies in depressed elderly patients.22,23 Navarro et al.22 examined the efficacy and tolerability of M-ECT with nortriptyline versus continuation pharmacotherapy (C-Pharm) with nortriptyline, with 2-year follow-up. Psychotic depressed patients older than 60 years, who had reached full remission after ECT, were included in the study. The primary outcome measure was time to relapse or recurrence using survival analysis. Over 2 years, the mean survival time of the M-ECT group was significantly
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longer than the pharmacotherapy group (23 months compared with 16 months [HR = 8.12, 95% CI: 1.5– 44.7]). Strong aspects of the study are the homogeneity of the study sample, geriatric patients with a psychotic depression only, and a long follow-up period. The study of Serra et al.23 had a similar design as Navarro et al.,22 but relapse/recurrence was only measured by a 2-year outcome. The relapse or recurrence rates at this point were significantly higher in the pharmacotherapy group with nortriptyline (54%) than in the group of M-ECT plus nortriptyline (17%) (χ 2 = 5.06, p = 0.0043). Although both studies have small sample sizes, the difference between relapse rates of M-ECT versus C-Pharm seems convincing. Kellner et al.21 studied the efficacy of M-ECT versus C-Pharm in the prevention of relapse in a large
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Electroconvulsive Therapy in Depressed Elderly Patients
TABLE 1.
Study
Design
Randomized Controlled Trials Longitudinal, Navarro randomized, et al.22 (2008) single blind: M-ECT or C-Pharm Longitudinal, Serra et al.23 (2006) randomized, single blind: M-ECT or C-Pharm Randomized, Kellner single blind: et al.21 (2005) M-ECT or C-Pharm
Prospective cohort studies Case series Wijkstra et al.24 (2000) Sigler et al.25 Case series (1998)
Group Size Diagnosis
Age Range (mean)
16 M-ECT 17 C-Pharm MDD plus psychotic
>60 (68)
6 M-ECT 13 C-Pharm MDD plus psychotic
>60
89 M-ECT 95 C-Pharm MDD
18–85 (57)
14: MDD 6: MDD
42–74 (64) 68–83 (73)
ECT Schedule (av. freq.) Electrode Placement Fix 1/w n:4, 1/2w n:2, 1/m n: 22 Bi Fix 1/w n:4, 1/2w n:2, 1/m n:22 Bi Fix 1/w n:4, 1/2w n:4, 1/m n:2 Bi
Outcome Measure Instruments Primary outcome: time relapse/ recurrence Instruments: HDRS
Mean survival time significant longer in M-ECT than C-Pharm.
Primary outcome: relapse/ recurrence Instruments: HDRS
Relapse/recurrence significant higher in C-Pharm than M-ECT.
Primary outcome: relapse Secondary outcome: cognition Instruments: HDRS
No significant differences in relapse M-ECT compared with C-Pharm No significant differences in time of relapse M-ECT compared with C-Pharm.
Flex Bi Fix 1/m U Flex (1/5.7w) —
Relapse Instruments: HRDS Relapse Instruments: HDRS, GAF Hospital admission Relapse/ recurrence Instruments: HDRS, BPRS
50% relapse.
Vanelle et al.26 (1994)
Case series
22: 15 MDD 7 BP
35–86 (70)
Thienhaus et al.27 (1990)
Case series
6: 5 MDD 1 BP
63–77 (71)
Flex (1/4.0w) U
Hospital admission Recovery Instruments: HDRS, GAF
Clarke et al.28 (1989)
Case series
27: 24 MDD 3 BD
26–80 (65)
Flex U/Bi
Hospital admission
Flex (1/2.5w) U/Bi
Hospital admission Bed occupancy
Retrospective cohort studies with matched comparison group Chart review, 19: 44–88 (71) Gupta et al.29 (2008) with matched MDD group: C-Therapy
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Outcome
All patients full remission and no relapse of MDD. Significant more time spent in hospital and episodes a year before M-ECT, compared with during M-ECT. 41% of patients no recurrence. Significant decline in average annual inpatients days with M-ECT. No significant decrease frequency of hospital admission and average length of hospital days. Significant more hospitalization noncompleters compared with M-ECT protocol completers. Significant reduction average bed occupancy M-ECT and post-M-ECT compared pre-M-ECT. Significant reduction mean admission rates M-ECT compared with pre-M-ECT. No significant difference admission rates and bed occupancy M-ECT and controls.
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TABLE 1.
(Continued)
Study Gagn´e et (2000)
Design al.30
Schwartz et al.31 (1995)
Group Size Diagnosis
Age Range (mean)
ECT Schedule (av. freq.) Electrode placement
Outcome Measure Instruments
Chart review, with matched group: C-Pharm
29: 23 MDD 6 BP
29–91 (65)
Fix 1/w n:4, 1/2w n:2, 1/m U/Bi
Time relapse/recurrence Hospital admission/days
Chart review, with matched group: A. No index ECT, response Pharm. B. C-Therapy
21: 17 MDD 4 BP
33–78 (57)
Flex (≤1/m) U
Hospital admission
53: 50 MDD 3 BP
65–92 (76)
Flex —
Hospital admission/days
Retrospective cohort studies Chart review O’Connor et al.32 (2010)
Odeberg et al.33 (2008)
Chart review
41: 25 MDD 15 BP
39–83 (63)
Flex (1/2w) U/Bi
Hospital admission/days
Lim34 (2006)
Chart review
67–94 (82)
Flex (1/2.0w) Bi
Hospital admission/days
Russell et al.35 (2003)
Chart review
17: 14 MDD 3 BP, psychotic dis. 43: 34 MDD 4 BP 5 SA
34–93 (74)
Flex (1/2.5w) Bi
Hospital days Depressive severity Instruments: GAF, HDRS
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Outcome Significant better 2 and 5 years surviving without relapse/recurrence M-ECT compared with controls. Significant longer mean illness-free survival time M-ECT compared with controls. No significant difference M-ECT and controls in frequency of hospitalization or hospital days. Significant decreased hospitalization M-ECT compared before index episode. Significant more M-ECT patients hospitalized than group A. No significant difference hospitalization M-ECT compared with group B. Significant sooner hospitalization group B compared with M-ECT. Significant reduction hospital days and hospitalizations 2 years after M-ECT compared with previous 2 years. Significant reduction hospital days, number hospitalized patients and hospitalizations 3 years after M-ECT compared with 3 years before. Significant lower admissions to hospital and hospital days following M-ECT. Significant improvement depressive symptoms during 1 year of M-ECT compared with before index ECT. And global functioning compared with starting M-ECT. Significant reduction number hospital days 1 year M-ECT compared with before index episode.
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Electroconvulsive Therapy in Depressed Elderly Patients
TABLE 1.
(Continued)
Study Kramer36
Design Chart review
(1999)
Group Size Diagnosis
Age Range (mean)
ECT Schedule (av. freq.) Electrode placement
Outcome Measure Instruments
Outcome
56: 24 MDD 10 D and axis 2 9 BP 3 SP 10 D and PD 26: 17 MDD 8 BP 1 SA
30–84
Flex Bi
Recovery
MDD 75% remained improved.
60–89 (73)
Flex U
Relapse/recurrence Hospital admission
Relapse of 35% in 12 months. Significant higher hospitalizations 12 months prior M-ECT compared with after M-ECT. 5 patients stopped treatment and had poor prognosis: 1 died, 1 chronic hospitalization, 3 rehospitalized. Significant more recurrences and mean weeks in hospital 3 years previous M-ECT compared with under M-ECT. 9% hospitalization in patients who continued M-ECT.
Beale et al.37 (1996)
Case series
Mirchandani et al.38 (1994)
Case series
9: 8 MDD 1 SA
62–85 (76)
Flex U/Bi
Hospital admission Recovery
Lˆ oo 39 (1991)
Case series
7: 5 MDD 1 BP 1 SA
56–86 (75)
Flex —
Hospital admission Instruments: HDRS, BPRS
Jaffe et al.40 (1990)
Case series
27–84 (68)
Flex U
Hospital admission Relapse Instruments: HDRS
Lˆ oo et al.41 (1990)
Case series
(69)
Flex —
Recovery
Thornton et al.42 (1990)
Chart review
32: 27 MDD 3 BP 2 OA 16: 10 MDD 5 BP 1 SA 10: 9 MDD 1 BP
50–74 (62)
Flex (1/4.1w) U
Hospital admission
12 patients improved by M-ECT. 4 patients did not improve by M-ECT. Significant less hospitalization 18 months after initiating M-ECT than during 18 months preceding.
Notes: Therapy—C-Pharm, continuation pharmacotherapy; C-Therapy: continuation therapy; M-ECT, maintenance electroconvulsive therapy. Diagnosis—BP: bipolar disorder; D: depressive disorder; MDD: major depressive disorder; OA: organic affective disorder; PD: Parkinson disease; SA: schizoaffective disorder; SP: schizophrenia. ECT schedule—Fix: fixed schedule; Flex: flexible schedule; W: week(s), by example: 1/2w is every 2 weeks a M-ECT session; M: month; N: number of M-ECT treatments in fixed schedule; (av. freq.): average frequency M-ECT treatment in flexible schedule. Electrode placement—U: unilateral; Bi: bilateral (bitemporal); —: no information. Instruments—GAF: global assessment of functioning; CGI-S, clinical global impression; HDRS/HAM-D, Hamilton Depression Rating Scale; MADRS, Montgomery-Asberg Depression Rating Scale; (M)MDE, (mini) mental state examination; mMMSE, modified mini mental state examination.
multicenter study from the Consortium for Research in ECT (CORE). After a course of ECT, 184 remitters of a unipolar depression were randomized to either M-ECT without psychotropic medication, or to C-Pharm. Pharmacotherapy consisted of lithium carbonate plus nortriptyline. All ages from 18 to 85 years old were enrolled, and the mean age was 57.1 ± 16.1 years. The primary outcome measure was
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relapse of depression rated by the 24-item Hamilton Depression Rating Scale (HDRS). After 6 months, 37% of M-ECT group relapsed, compared with 32% of the C-Pharm group, not a statistically significant difference (χ 2 = 1.05; p = 0.59). Neither was a statistically significant advantage present for M-ECT for time of relapse, 9.1 ± 7.0 weeks compared with 6.7 ± 4.6 weeks for the C-Pharm (HR = 1.2, 95% CI: 0.7–1.9).
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van Schaik et al. From the CORE study, it can be concluded that, irrespective of which form of maintenance treatment is used, relapse rates after an ECT course are very high and consistent with the results found in the study of Sackeim et al.5 The strengths of this study are the large intention-to-treat sample of 184 patients and the rigorous design for randomization and administrating ECT. Although the vast majority of relapse after successful ECT occurs within the first 4 months,5 one could argue that a 6-month period for follow-up is relatively short. Prospective Studies Five prospective studies met all inclusion criteria for this review. In a naturalistic follow-up study by Wijkstra et al.,24 pharmacotherapy-resistant unipolar depressed patients, who had responded well to ECT, were treated with M-ECT only. The relapse rate was 50% in 6 months (95% CI: 21–79). Relapse was defined as a depressive episode according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, a HDRS score of at least 14 and HDRS scores 50% or more of the baseline score before ECT. Six geriatric patients in a case series by Sigler et al.25 received M-ECT once a month, during at least 6 months. They were all refractory to pharmacotherapy and had on average four relapses before M-ECT was administered. In 6 months, no relapse occurred, as measured by HDRS. Vanelle et al.26 studied patients with unipolar or bipolar disorders for an average of 18 months. Most patients had somatic comorbidity and a long duration of illness. The mean duration of illness was 26 years. They all suffered from pharmacotherapyresistant depression with at least two tricyclic antidepressants and a mood stabilizer or presented contraindications prohibiting pharmacotherapy. In 1 year prior to M-ECT, patients spent on average 44% of the year in the hospital with at least three episodes a year. During M-ECT, 7% of the year was spent in hospital (p <0.001) with less than one relapse every 16 months requiring admission (p <0.001). Among the patients with a major depression, only 60% were in full or partial remission. There was a tendency for a better response in persons with mood disorders with psychotic features. Besides, 45% of patients had a period with more frequent ECT sessions because of worsening in condition.
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In a case series of Thienhaus et al.27 six patients with a very long duration of illness, averaging 22 years, were followed from 1 to 6 years. Four of six patients had a decrease in frequency and duration of hospital admission and improved on all rating scales for depression, cognition, and functional impairment after applying M-ECT. The decline in average annual inpatients days was significant. Clarke et al.28 described a study of patients who received M-ECT without medication. Eight percent of the M-ECT completers relapsed and needed hospitalization, compared with 47% of the patients who failed to complete the protocol (p = 0.04). It was not reported why patients did not complete the protocol. Stopping M-ECT can be a result of relapse and secondary lack of motivation or side effects. Retrospective Studies With Matched Comparison Group Three retrospective studies with a matched comparison group were found. Gupta et al.29 studied patients who proceeded to M-ECT after a positive response on index ECT, compared with a comparison group, matched for sex, age, diagnosis, and time of index ECT. The patients in the comparison group were offered “treatment as usual” after index ECT. The hospital admission rates and bed occupancy did not differ between the two groups. In the M-ECT group, the mean hospital admission rate reduced significantly during the period of M-ECT, compared with the period before the initiation of M-ECT: 1.00 admissions a year compared with 0.316 admissions a year (p <0.001). The bed occupancy was lower in the M-ECT group during treatment (7.05 weeks/year) than in pre-M-ECT (14.05 weeks/year) (p = 0.055). Gagn´e et al.30 reported about patients on M-ECT with pharmacotherapy. The comparison group consisted of patients who received C-Pharm after index ECT, matched on age, gender, diagnosis, age of onset, comorbid psychosis, and year of index ECT course. The mean duration of follow-up was 5.4 years for the M-ECT group. After 2 years, the cumulative probability of remission was 93% in M-ECT compared with 52% in the comparison group. After 5 years, 73% of M-ECT patients had no relapse in contrast with 18% of the comparison group (χ 2 = 19.87, p <0.0001). The mean illness-free time was 6.9 (95% CI: 5.1–8.0) years for M-ECT compared with 2.7 (95% CI: 1.7–3.6) years
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Electroconvulsive Therapy in Depressed Elderly Patients for C-Pharm. Frequency of hospitalization or number of hospital days did not differ between groups. Strengths of this study are the carefully matched comparison group, the long follow-up period, and the use of a structured M-ECT schedule. Schwartz et al.31 studied M-ECT in patients and two comparison groups that were matched on sex, race, diagnosis, and date of admission. The first comparison group consisted of depressed patients who recovered with only pharmacotherapy. The second comparison group received alternative treatment after a successful course of ECT. The rate of rehospitalization of patients receiving M-ECT compared with the period before index episode was significantly reduced by 67% (p ≤0.05). More M-ECT patients than the first comparison group were rehospitalized during follow up, 71% versus 45% (χ 2 = 6.15, p ≤0.05). The second comparison group did not differ significantly in hospitalization compared with M-ECT, but relapsed sooner, 8 versus 16 months (H = 13.7, p <0.05). A major problem in this study is that the patient groups are difficult to compare. Retrospective Studies Without Comparison Group Eleven studies were found. O’Connor et al.32 reports of 53 patients of three geriatric psychiatric services. They received M-ECT on one or more occasions, with a mean of 15 treatments. In the 2 years after the M-ECT started, the number of hospital admissions significantly fell down by 53% in number and 79% in duration, compared with the previous 2 years. The study of Odeberg et al.33 was a chart review of patients who received M-ECT and pharmacotherapy for more than 4 months. M-ECT was individually tapered. The need for hospital care 3 years before and 3 years after M-ECT were compared. The total number of hospital days was reduced by 76% (p <0.001). Also the number of patients hospitalized and the number of admissions in hospital both were significantly reduced by 64% (p <0.0001). Major limitations in this study are incomplete hospital records, lacking instruments to measure relapse, and change of medication and frequency of ECT during the study. Lim34 described an audit of patients receiving M-ECT with a duration range of 3 to 60 months. Patient selection is somewhat unusual, because 29% patients received ECT involuntarily. A comparison
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was made of clinical outcome measures for an equivalent period of time before and after M-ECT. The number of admissions to hospital and length of stay in the hospital following the M-ECT were lower than those before the start of M-ECT (p <0.015) (p <0.010). In a chart review by Russell et al.,35 43 patients received M-ECT for more than a year. The result was a significant decrease in the number of hospital days from 18.95 days to 3.23 days per patient per year (p <0.001). The Global Assessment of Functioning significantly improved after M-ECT, 48.0 versus 55.51 (p = 0.012). Also, HDRS generally improved after starting M-ECT, 29.1 versus 6.1 (p <0.001), but was available for only 11 patients and measured the period before index episode and after 1-year M-ECT. Kramer36 reviewed patient charts during 4.5 years of a university ECT service. Patients with a major depressive disorder benefited from M-ECT, 75% remained free of relapse or recurrence measured by clinical assessment. Information of 1-year follow up in a M-ECT clinic by Beale et al.37 showed 4% relapse after 3 months, 25% at 6 months, and 35% at 12 months using survival analyses. There was a significant decrease in the mean number of hospitalization 12 months prior to M-ECT, 1.8 hospitalization per patient, compared with 12 months following initiation of M-ECT, 0.23 hospitalization per patient (p = 0.0001). Mirchandani et al.38 described 9 geriatric patients referred for M-ECT. Four patients who complied with M-ECT remained well during followup until 1 year. The 5 patients who stopped treatment ˆ et al.39 described a group had negative outcomes. Loo of patients who received M-ECT for nearly 3 years. All patients had significantly fewer hospitalization and recurrences during M-ECT compared with the previous 3 years. In an outpatient ECT clinic, Jaffe et al.40 found that two-third of the patients continued the ECT treatment without requiring hospitalization or had been successfully discharged from treatment. ˆ et al.41 12 of 16 patients with In a case series of Loo a therapy-resistant depression improved by M-ECT according to the clinician. Thornton et al.42 identified 10 patients treated with M-ECT in a university-based ECT service. Most of the patients were suffering from a psychotic depression. There were fewer hospital admissions in the 18 months after initializing M-ECT, with a mean of 0.3 compared with a mean of 3.1 hospital admissions in the 18 months preceding M-ECT (p <0.001).
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SAFETY OF M-ECT Cognition Cognitive problems are an important side effect of M-ECT. Because cognitive decline is associated with aging and with age-related diseases, older people may be more vulnerable to cognitive impairment. Seven studies measured cognitive functioning before and after M-ECT but only with global screening instruments like the Mini-Mental State Examination (MMSE) or the Mental State Examination (MSE). None of these studies reported cognitive problems. In the study of Kellner and colleagues,21 the secondary outcome was cognitive functioning, measured by the modified MMSE (mMMSE), a more expanded instrument compared with the MMSE. Mean scores did not differ significantly at the end of the study (C-Pharm: 49.1 ± 0.5; M-ECT: 48.4 ± 0.5). The mMMSE score improved for both groups during 6 months. A review on the effects of ECT on cognitive functioning in the elderly patients gave information of cognitive effects during M-ECT on the basis of three studies. Global cognitive functioning, as measured with the MMSE, remained stable after receiving M-ECT over at least a year, whereas learning verbal information and executive functioning was impaired, compared to a group of matched patients who had never received ECT.43 Recently, data from the CORE study were published in which memory effects of M-ECT versus C-Pharm were compared at 12 and 24 weeks to baseline in 85 patients who completed the course without relapse.44 At 12 weeks, patients on M-ECT had lower scores on a retrograde memory test compared to C-Pharm (p <.01), but after 24 weeks these differences disappeared.
Physical Comorbidity Although several studies included a large group of patients with somatic comorbidity such as cardiac or neurological conditions, M-ECT was generally well tolerated because none of them caused significant morbidity or interfered with further ECT.26,32,35,38, 40–42 Falls, delirium and cardiac problems were described in the studies of Russell et al.,35 Jaffe et al.,40 and Vanelle et al.26 as temporary physical reactions to ECT.
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In the three randomized trials, all patients with central nervous system disease and somatic conditions complicating therapy were excluded. In the studies of Navarro et al.22 and Serra et al.,23 changes of diastolic and systolic blood pressure, electrocardiographic intervals, and heart rate were measured. Side effects were assessed by the Udvalg for Kliniske Undersogelse Side-Effect Rating Scale. Both treatments, M-ECT with nortriptyline and nortriptyline as C-Pharm, were well tolerated. No significant differences in Udvalg for Kliniske Undersogelse scores, or changes in electrocardiographic intervals, heart rate, or blood pressure were found. In the study of Kellner and colleagues,21 adverse effects were noted. Two patients from the M-ECT group, who dropped out of the study, complained of memory loss and headache, whereas 13 patients who received C-Pharm stopped because of adverse reactions to medication.
DISCUSSION Although research on this clinically important topic is sparse, we were able to select 22 studies meeting inclusion criteria. The majority was published recently, reflecting a growing interest of clinicians in MECT. To date, only 3 randomized controlled trials were performed, whereas this method is considered the best way to study the effectiveness of treatment. From these studies, one might conclude that M-ECT has a comparable efficacy as C-Pharm in the prevention of relapse or recurrence of a depressive episode. The study of Navarro et al.,22 however, yielded better outcome during the first months than the CORE study and continued to do so during the 2 years of M-ECT. These differences can neither be explained by patient selection in the Navarro-trial (psychotic depression and an age above 60 years) because adjustment for the covariables psychosis and age did not change the effect significantly in the CORE study, nor by the ECT procedures, because in both studies bilateral treatment and a fixed MECT schedule were applied. A possible explanation for the better results of M-ECT by Navarro et al.22 could be the additional pharmacotherapy with nortriptyline.45 The notion that M-ECT with addition of nortriptyline was well tolerated in this geriatric population is comforting. In the study of Navarro et al.22 and Serra et al.,23 a shorter time until
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Electroconvulsive Therapy in Depressed Elderly Patients relapse was found for the C-Pharm group compared to the M-ECT group; the same trend was seen in the CORE study, although it did not reach significance (p = 0.13). The five prospective studies are difficult to compare because they use different methods for patient selection, depression measurements, length of treatment, pharmacotherapy, and ECT-procedures. The majority of patients were medication-resistant.24–26,28 The relapse rate of patients with medication-resistant depression with M-ECT of 50% in the Wijkstra et al.24 study did not differ from the results of the CORE study. A cautious conclusion from these studies is that M-ECT could also be effective in medicationresistant elderly patients or in elderly patients with a long illness duration. M-ECT was especially profitable in terms of hospitalization compared with the period before M-ECT. Three retrospective studies with matched comparison groups describe their M-ECT population as more severely ill, with a larger number of admissions, more psychotropic medication, or more previous ECT. Despite careful matching, selection bias seems thus inevitable. All studies show a significant decrease of hospitalization after starting M-ECT compared with earlier periods. Significant differences in hospitalization or relapse of M-ECT compared with matched patients, however, could not be demonstrated. Eleven retrospective studies without matched comparison groups were found, all with severe methodological limitations. Despite the referral of more severely and chronically ill patients to M-ECT, all studies showed improvement after M-ECT, measured by hospital admission or clinical outcome. Considering efficacy, from the three randomized trials,21–23 it can be concluded that M-ECT and C-Pharm have comparable efficacy. The clinician should note, however, that this can only be concluded for M-ECT using a fixed treatment schedule. It is very well possible that RCTs using a fixed schedule underestimate the effectiveness of M-ECT. In clinical practice, treatment frequency is commonly increased when the patient shows signs of relapse. It seems reasonable to assume that patients might benefit from an individual approach when the intertreatment interval based on (early) signs of relapse is flexible. In most of the prospective and retrospective studies,28,36,37,40 this flexible approach was used, yielding impressive results. Nevertheless, from the current randomized
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evidence, the superiority of M-ECT cannot be concluded. After a successful ECT course, therefore, CPharm should be continued for relapse prevention. Should C-Pharm fail, M-ECT is to be considered. A limitation of a review on this topic is the lack of well-controlled studies, not allowing a meta analysis of randomized evidence. We chose to study all relevant studies on this subject and included studies with different methodology, sample size, and patient selection like age and sample size, hampering comparison between studies and firm conclusions, but providing a fair overview of the efficacy and safety of M-ECT for these patients. Publication bias may have lead to a more favorable view on the efficacy of M-ECT in this review, particularly due to the noncontrolled studies. Nevertheless, naturalistic studies were also included despite their severe methodological limitations, as open prospective and retrospective studies may represent daily practice reasonably well. Performing an RCT with elderly depressed patients after an index episode of ECT is met by special difficulties as costs, number of subjects that should be enrolled and the issue of comorbidity. For elderly patients with medical comorbidity and comedication, randomization is often very difficult. Finally, choosing a relative low mean age of 55 years and older, limits the generalizability of our findings to the oldest old. The same applies to safety aspects especially in the oldest old who may be more at risk for cardiovascular complications and cognitive impairment. Cognitive functioning, an important clinical issue geriatric depression, has not been studied properly to date. In two studies, no significant differences were found between cognitive functioning of patients treated with M-ECT and control patients treated with M-Pharm after index ECT, but neither long-term effects were studied nor older old patients.44,46 Despite the common physical comorbidity, M-ECT was generally well tolerated with only rare physical complications indicating the relative safety of this treatment modality. According to our findings, the discouragement by the National Institute for Clinical Excellence to practice M-ECT, because evidence is lacking for long-term benefits and because of potential risks of M-ECT, is too conservative.47 The notion of the American Psychiatric Association task force that M-ECT should be available in centers practicing ECT is supported by our study and more in line with clinical
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van Schaik et al. practice.6 But then, again the suggestion that M-ECT should be offered as a standard of care after an index episode of depression treated with ECT as an alternative for medication in depressed elderly patients was also not supported by our study. For clinicians, it is important that M-ECT is available when treating severely depressed elderly patients after improvement with index ECT in case of prior relapse while on adequate C-Pharm, in case of medication intolerance, or patient’s preference.17,48,49 This review gives rise to several questions and topics for further research on M-ECT. Which M-ECT technique and procedure is most effective in preventing the relapse or recurrence of a depressive disorder after successful ECT? As discussed earlier, more research is needed as to which treatment schedule, fixed or flexible, is superior. To our knowledge, studies examining this issue are ongoing.50,51 The three RCTs used bilateral placement and all studies published in the last 10 years used bilateral placement or a combination. Although bilateral placement is considered more effective in acute ECT, whether this applies for M-ECT, remains elusive.2,52 In different studies, different placements were used, but no study has compared electrode placements during M-ECT. Although a recent CORE-trial, comparing bitemporal, bifrontal, and unilateral ECT, failed to show significant differences between the three techniques, it is conceivable that during M-ECT the electrode placement used, in combination with stimulus dose and stimulus parameters, may have effects on treatment efficacy and, perhaps even more, on cognitive side effects.52 Because bilateral treatment might confer a greater risk of cognitive impairments,
especially relevant in old age, many geriatric psychiatrists prefer unilateral placement currently.53,54 Another question is whether M-ECT should be combined with additional continuation pharmacotherapy. The study of Navarro et al.22 suggests that M-ECT with nortriptyline might provide better prevention of relapse. In a recent study of Sackeim et al.,45 concomitant pharmacotherapy was given during an ECT course. Addition of nortriptyline enhanced the efficacy with a 15% increase in remission rate and reduced the cognitive side effects, with respect to placebo. Furthermore, little is known about which clinical characteristics predict a positive response on M-ECT. From the selected studies, old age, psychotic symptoms, medication resistance, or physical illness did not predict negative response on M-ECT treatment. In addition, patient and family perspective and compliance should be studied more with regard to M-ECT.55 Patients’ dislike of the treatment or preference, logistic problems when living at home or in a institutional setting, social support, and the required repeated anesthesia are worth mentioning. Evaluation of M-ECT programs in this respect are lacking. Finally, more information about cost-effectiveness of M-ECT is needed. In a cost utility analysis by Aziz et al.,56 the costs and outcomes of M-ECT differed favorably from those of C-Pharm in a theoretical cohort of elderly patients with a recurrent major depressive disorder. In conclusion, this review summarizes the available research of M-ECT in geriatric depression. According to our results, M-ECT can be an important treatment option for relapse prevention in severely depressed elderly patients.
References 1. Wurff van der FB, Stek M, Hoogendijk WJG, et al: The efficacy and safety of ECT in depressed older adults: a literature review. Int J Geriatr Psychiatry 2003; 34:894–904 2. Greenberg RM, Kellner CH: Electroconvulsive therapy a selected review. Am J Geriatr Psychiatry 2005: 13:268–281 3. Tew JD, Mulsant BH, Haskett RF, et al: Acute efficacy of ECT in the treatment of major depression in the old-old. Am J Psychiatry 1999; 156:1865–1870 4. O’Connor MF, Knapp R, Husain M, et al: The influence of age on the response of major depression to electroconvulsive therapy. Am J Geriatr Psychiatry 2001; 9:382–390 5. Sackeim HA, Haskett RF, Mulsant BH: Continuation pharmacotherapy in the prevention of relapse following electrocon-
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vulsive therapy: a randomized controlled trail. JAMA 2001; 285:1299–1307 6. American Psychiatric Association Committee on Electroconvulsive Therapy. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training and Privileging, 2nd ed. Washington, DC, American Psychiatric Association, 2001 7. Olfson M, Marcus S, Sackeim, et al: Use of ECT for the inpatient treatment of recurrent major depression. Am J Psychiatry 1998; 155:22–29 8. Cole MG, Bellavance F, Mansour A: Prognosis of depression in elderly community and primary care population: a systematic review and meta-analysis. Am J Psychiatry 1999: 156: 1182–1189
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antidepressants alone in depressed patients. Am J Psychiatry 2000; 157:1960–1965 Schwartz T, Loewenstein J, Isenburg K: Maintenance ECT: indications and outcome. Convuls Ther 1995; 11:14–23 O’Connor DW, Gardner B, Presnell I, et al: The effectiveness of continuation-maintenance ECT in Reduced depressed older patients’ hospital re-admissions. J Affect Disord 2010; 120: 62–66 Odeberg H, Rodriguez-Silva B, Salander P, et al: Individualized continuation electroconvulsive therapy and medication as a bridge to relapse prevention after course of electroconvulsive therapy in severe mood disorder: a naturalistic 3 year cohort study. J ECT 2008; 24:183–190 Lim LM: A practice audit of maintenance electroconvulsive therapy in the elderly. Int Psychogeriatr 2006; 18:751–754 Russell JC, Rasmussen KG, O’Connor MK, et al: Long term maintenance ECT: a retrospective review of efficacy and cognitive outcome. J ECT 2003; 19:4–9 Kramer BA: A naturalistic review of maintenance ECT at a university setting. J ECT 1999; 15:262–269 Beale MD, Bernstein HJ, Kellner CH, et al: Maintenance electroconvulsive therapy for geriatric depression: a year follow-up. Clin Gerontol 1996; 16:86–90 Mirchandani IC, Abrams RC, Young RC, et al: One-year followup of continuation convulsive therapy prescribed for depressed elderly patients. Int J Geriatric Psychiatry 1994; 9:31–36 Lˆ oo H, Galinowski A, Carvalho de W, et al: Use of maintenance ECT for elderly depressed patients. Am J Psychiatry 1991; 148:810. Jaffe R, Dubin W, Shoyer B, et al: Outpatient electroconvulsive therapy: efficacy and safety. Convuls Ther 1990; 6:231–238 Lˆ oo H, de Carvalho W, Galinowski A: Towards the rehabilitation of maintenance electroconvulsive therapy. Ann Med Psychol; 1990; 148:1–15 Thornton JE, Mulsant BH, Dealy R, et al: A retrospective study of maintenance electroconvulsive therapy in a university-based psychiatric practice. Convuls Ther 1990; 6:121–129 Tielkens CEM, Comijs HC, Verwijk E, et al: The effect of ECT on cognitive functioning in the elderly: a review. Int J Geriatr Psychiatry 2008; 23:789–795 Smith GE, Rasmussen KG, Cullum M, et al: A randomized controlled trial comparing the memory effects of continuation electroconvulsive therapy versus continuation pharmacotherapy: results from the Consortium for Research in ECT (CORE) study. J Clin Psychiatry 2010: 71:185–193 Sackeim HA, Dillingham EM, Prudic J, et al: Effect of Concomitant Pharmacotherapy on Electroconvulsive Therapy Outcomes: short-term Efficacy and Adverse Effects. Arch Gen Psychiatry 2009; 66:729–737 Vothknecht S, Kho KH, Schaick HW, et al: Effects of maintenance electroconvulsive therapy on cognitive functions. J ECT 2003: 19:151–157 National Institute of Clinical Excellence. Guidelines on the use of Electroconvulsive Therapy. London: Department of Health; 2003 Chanpattana W, Kramer BA, Kunigiri G, et al: A survey of the practice of electroconvulsive therapy in Asia. J ECT 2010; 26: 5–10 Sienaert P, Dierick M, Degraeve G, et al: Electroconvulsive therapy in Belgium: a nationwide survey on the practice of electroconvulsive therapy. J Affect Disord 2006; 60:67–71 Kellner C, Lisanby SH: Flexible dosing schedules for continuation electroconvulsive therapy. J ECT 2008; 24:117–118
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van Schaik et al. 51. Lisanby SH, Sampson S, Husain MM, et al: Toward individua lized post-electroconvulsive therapy care: piloting the SymptomTitrated, algorithm-Based Longitudinal ECT (STABLE) intervention. J ECT 2008; 23:179–182 52. Kellner CH, Knapp R, Husain MM, et al: frontal, bitemporal and right unilateral electrode placement in ECT: a randomised trial. Br J Psychiatry 2010; 196:226–234 53. O’Connor DW, Gardner B, Eppingstall B, et al: Cognition in elderly patients receiving unilateral and bilateral electroconvulsive therapy: a prospective naturalistic comparison. J Affect Disord 2010; 124:235–240
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54. Sackeim HA, Prudic J, Nobler MS, et al: Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. Brain Stim 2008; 1:71–83 55. Kim E, Zisselman MH, Pelchat R: Factors affecting compliance with maintenance electroconvulsive therapy: a preliminary study. Int J Geriatr Psychiatry 1996; 11:473–476 56. Aziz M, Mehringer AM, Mozurkewich E, et al: Cost-utility of two maintenance treatments for older adults with depression who responded to a course of electroconvulsive therapy: results from a decision analytic model. Can J Psychiatry 2005; 50: 389–397
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Efficacy and Safety of Continuation and Maintenance Electroconvulsive Therapy in Depressed Elderly Patients: A Systematic Review Audrey M. van Schaik, M.D., Hannie C. Comijs, Ph.D., Caroline M. Sonnenberg, M.D., Aartjan T. Beekman, M.D., Ph.D., Pascal Sienaert, M.D., Ph.D., Max L. Stek, M.D., Ph.D.
Background: Electroconvulsive therapy (ECT) is the most efficacious treatment in severely depressed elderly patients. Relapse and recurrence of geriatric depression after recovery is an important clinical issue, which requires vigorous and safe treatment in the long term. Continuation or maintenance ECT (M-ECT) may play an important role in this respect. Methods: In this systematic search, we evaluate the efficacy and safety of M-ECT in preventing depressive relapse in patients age 55 or older. Computer databases were searched for relevant literature published from 1966 until August 2010 with additional references. Results: Twenty-two studies met the search criteria including three randomized clinical trials. M-ECT was studied in nine studies exclusively in the elderly patients. Conclusions: Research on this clinically important topic is sparse. On the basis of available literature, M-ECT is probably as effective as continuation medication in severely depressed elderly patients after a successful course of ECT and is generally well tolerated. To date, methodologically sound studies, which take into account important issues in geriatric depression like cognition, comorbidity, and clinical parameters, are lacking. (Am J Geriatr Psychiatry 2012; 20:5–17) Key Words: Continuation, depressive disorder, ECT, elderly, electroconvulsive therapy, geriatric, maintenance, major depression, review
E
lectroconvulsive therapy (ECT) is an effective and safe treatment for severe depression.1,2 In depressed elderly patients, ECT may have an even higher immediate response rate than in younger patients.3,4 After successful treatment with ECT, the
prevention of relapse and recurrence of a new depressive episode is very important. Without pharmacotherapy, 85% of the patients relapse in the first 6 months after successful ECT and even with medication relapse rates are approximately 50%.5
Received April 7, 2010; revised November 4, 2010; accepted November 7, 2010. From the GGZ inGeest/VU University Medical Center, Amsterdam, the Netherlands (AMvS, HCC, CMS, ATB, MLS); and University Psychiatric Center, Catholic University of Leuven, Campus Kortenberg, Belgium (PS). No sources of support. Send correspondence and reprint requests to Audrey M. van Schaik, M.D., GGZ inGeest, Valeriusplein 14, 1075 BH Amsterdam, the Netherlands. e-mail: [email protected] c 2011 American Association for Geriatric Psychiatry DOI: 10.1097/JGP.0b013e31820dcbf9
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Electroconvulsive Therapy in Depressed Elderly Patients Consequently, all patients successfully treated with ECT nowadays use antidepressants or get maintenance or continuation ECT, afterwards, or both to reduce this risk. Continuation ECT is defined as treatment over 6 months after the remission of an index episode of depression to prevent relapse. Electroconvulsive therapy after this 6-month period has been called maintenance ECT and does not have a fixed end point.6 In this review, the term maintenance ECT (M-ECT) will be used referring to both continuation and maintenance ECT. Depressed elderly patients are treated with acute ECT more often than younger adults for several reasons.7 First, they often have poor tolerance to pharmacotherapy in the presence of comorbid physical problems, such as cardiovascular disease, and the related frequent use of multiple drugs. Second, severe depression leads more often to life-threatening conditions in frail elderly patients requiring a fast treatment response.8 Generally, elderly patients are more at risk for relapse of depression after successful treatment, which may be caused by medical comorbidity and a higher likelihood of previous depression in the elderly patients.8 Furthermore, the high frequency of treatment-resistant depression and psychotic depression in old age contributes to higher relapse rates after ECT.9–11 Consequently, elderly patients are probably more referred to M-ECT. Although M-ECT needs repetitive anesthesia, it is difficult to organize in many places, is expensive, and can be burdensome especially for frail elderly patients and their relatives. In daily practice, choices for relapse preventing treatment should be based on clinical experience and research. To date, no systematic review was done on the efficacy and safety of M-ECT in the prevention of relapse or recurrence of depressive episodes in the elderly patients. Previous reviews on M-ECT included studies in all age groups or a broader range of psychiatric disorders, such as bipolar disorder and schizophrenia.12–20 The objective of this study is to review the research on the efficacy and safety of M-ECT in depressed elderly patients.
METHODS Selection of articles involved three steps. First, the computer databases MEDLINE, Cochrane, Embase, and Psychinfo were searched for published studies in the period from 1966 to August 2010. “Mainte-
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nance electroconvulsive therapy” or “continuation electroconvulsive therapy” or “maintenance ECT” or “continuation ECT” in combination with “depressive disorder” or “major depression” were used as key words. Second, relevant articles (based on title and abstract) were screened manually and their bibliographies were searched for additional references to identify studies on M-ECT. Third, all retrieved articles were screened to meet the following inclusion criteria: 1. Studies on maintenance or continuation ECT as intervention to prevent relapse or recurrence of depression. 2. Studies on M-ECT in affective disorders with at least 50% of the patients diagnosed with unipolar depression. 3. Subjects’ mean age 55 years or more. 4. A minimum of 5 patients with unipolar depression in the study group or case series. 5. Evaluation of the efficacy of M-ECT. Randomized clinical trails (RCTs) and prospective and retrospective cohort studies were included for the review. The first author (AMvS) and one of the coauthors (MLS) read the abstracts to determine their relevance to the review. In the next step, the manuscript was screened to examine whether criteria for age, minimum number of patients, and the presence of standardized evaluation were met. No selection in language was made. If there was insufficient information in the study with regard to one or more of the criteria, we tried to contact the authors for additional information.
RESULTS The data search by key words yielded 125 potentially relevant articles. Additional 21 studies were found by cross-referencing. In Figure 1, we show the flow diagram of the selection of the studies for this review. A total of 124 studies were excluded resulting in 22 studies meeting all the selection criteria. From these studies, 9 studies included exclusively patients older than 55 years. The other 13 studies included adult patients (age range, 18–94), but with a mean age of 55 years or older. This procedure identified 3 RCTs, 5 prospective cohort studies, 3 retrospective cohort studies with a matched comparison group, and 11 retrospective cohort studies (Table 1).
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van Schaik et al.
FIGURE 1.
Flow diagram of selection of studies.
EFFICACY OF M-ECT Randomized Clinical Trials Three RCTs with a different methodology were found, one large multicenter trial in all age categories of Kellner and colleagues21 and two smaller studies in depressed elderly patients.22,23 Navarro et al.22 examined the efficacy and tolerability of M-ECT with nortriptyline versus continuation pharmacotherapy (C-Pharm) with nortriptyline, with 2-year follow-up. Psychotic depressed patients older than 60 years, who had reached full remission after ECT, were included in the study. The primary outcome measure was time to relapse or recurrence using survival analysis. Over 2 years, the mean survival time of the M-ECT group was significantly
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longer than the pharmacotherapy group (23 months compared with 16 months [HR = 8.12, 95% CI: 1.5– 44.7]). Strong aspects of the study are the homogeneity of the study sample, geriatric patients with a psychotic depression only, and a long follow-up period. The study of Serra et al.23 had a similar design as Navarro et al.,22 but relapse/recurrence was only measured by a 2-year outcome. The relapse or recurrence rates at this point were significantly higher in the pharmacotherapy group with nortriptyline (54%) than in the group of M-ECT plus nortriptyline (17%) (χ 2 = 5.06, p = 0.0043). Although both studies have small sample sizes, the difference between relapse rates of M-ECT versus C-Pharm seems convincing. Kellner et al.21 studied the efficacy of M-ECT versus C-Pharm in the prevention of relapse in a large
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Electroconvulsive Therapy in Depressed Elderly Patients
TABLE 1.
Study
Design
Randomized Controlled Trials Longitudinal, Navarro randomized, et al.22 (2008) single blind: M-ECT or C-Pharm Longitudinal, Serra et al.23 (2006) randomized, single blind: M-ECT or C-Pharm Randomized, Kellner single blind: et al.21 (2005) M-ECT or C-Pharm
Prospective cohort studies Case series Wijkstra et al.24 (2000) Sigler et al.25 Case series (1998)
Group Size Diagnosis
Age Range (mean)
16 M-ECT 17 C-Pharm MDD plus psychotic
>60 (68)
6 M-ECT 13 C-Pharm MDD plus psychotic
>60
89 M-ECT 95 C-Pharm MDD
18–85 (57)
14: MDD 6: MDD
42–74 (64) 68–83 (73)
ECT Schedule (av. freq.) Electrode Placement Fix 1/w n:4, 1/2w n:2, 1/m n: 22 Bi Fix 1/w n:4, 1/2w n:2, 1/m n:22 Bi Fix 1/w n:4, 1/2w n:4, 1/m n:2 Bi
Outcome Measure Instruments Primary outcome: time relapse/ recurrence Instruments: HDRS
Mean survival time significant longer in M-ECT than C-Pharm.
Primary outcome: relapse/ recurrence Instruments: HDRS
Relapse/recurrence significant higher in C-Pharm than M-ECT.
Primary outcome: relapse Secondary outcome: cognition Instruments: HDRS
No significant differences in relapse M-ECT compared with C-Pharm No significant differences in time of relapse M-ECT compared with C-Pharm.
Flex Bi Fix 1/m U Flex (1/5.7w) —
Relapse Instruments: HRDS Relapse Instruments: HDRS, GAF Hospital admission Relapse/ recurrence Instruments: HDRS, BPRS
50% relapse.
Vanelle et al.26 (1994)
Case series
22: 15 MDD 7 BP
35–86 (70)
Thienhaus et al.27 (1990)
Case series
6: 5 MDD 1 BP
63–77 (71)
Flex (1/4.0w) U
Hospital admission Recovery Instruments: HDRS, GAF
Clarke et al.28 (1989)
Case series
27: 24 MDD 3 BD
26–80 (65)
Flex U/Bi
Hospital admission
Flex (1/2.5w) U/Bi
Hospital admission Bed occupancy
Retrospective cohort studies with matched comparison group Chart review, 19: 44–88 (71) Gupta et al.29 (2008) with matched MDD group: C-Therapy
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Outcome
All patients full remission and no relapse of MDD. Significant more time spent in hospital and episodes a year before M-ECT, compared with during M-ECT. 41% of patients no recurrence. Significant decline in average annual inpatients days with M-ECT. No significant decrease frequency of hospital admission and average length of hospital days. Significant more hospitalization noncompleters compared with M-ECT protocol completers. Significant reduction average bed occupancy M-ECT and post-M-ECT compared pre-M-ECT. Significant reduction mean admission rates M-ECT compared with pre-M-ECT. No significant difference admission rates and bed occupancy M-ECT and controls.
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van Schaik et al.
TABLE 1.
(Continued)
Study Gagn´e et (2000)
Design al.30
Schwartz et al.31 (1995)
Group Size Diagnosis
Age Range (mean)
ECT Schedule (av. freq.) Electrode placement
Outcome Measure Instruments
Chart review, with matched group: C-Pharm
29: 23 MDD 6 BP
29–91 (65)
Fix 1/w n:4, 1/2w n:2, 1/m U/Bi
Time relapse/recurrence Hospital admission/days
Chart review, with matched group: A. No index ECT, response Pharm. B. C-Therapy
21: 17 MDD 4 BP
33–78 (57)
Flex (≤1/m) U
Hospital admission
53: 50 MDD 3 BP
65–92 (76)
Flex —
Hospital admission/days
Retrospective cohort studies Chart review O’Connor et al.32 (2010)
Odeberg et al.33 (2008)
Chart review
41: 25 MDD 15 BP
39–83 (63)
Flex (1/2w) U/Bi
Hospital admission/days
Lim34 (2006)
Chart review
67–94 (82)
Flex (1/2.0w) Bi
Hospital admission/days
Russell et al.35 (2003)
Chart review
17: 14 MDD 3 BP, psychotic dis. 43: 34 MDD 4 BP 5 SA
34–93 (74)
Flex (1/2.5w) Bi
Hospital days Depressive severity Instruments: GAF, HDRS
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Outcome Significant better 2 and 5 years surviving without relapse/recurrence M-ECT compared with controls. Significant longer mean illness-free survival time M-ECT compared with controls. No significant difference M-ECT and controls in frequency of hospitalization or hospital days. Significant decreased hospitalization M-ECT compared before index episode. Significant more M-ECT patients hospitalized than group A. No significant difference hospitalization M-ECT compared with group B. Significant sooner hospitalization group B compared with M-ECT. Significant reduction hospital days and hospitalizations 2 years after M-ECT compared with previous 2 years. Significant reduction hospital days, number hospitalized patients and hospitalizations 3 years after M-ECT compared with 3 years before. Significant lower admissions to hospital and hospital days following M-ECT. Significant improvement depressive symptoms during 1 year of M-ECT compared with before index ECT. And global functioning compared with starting M-ECT. Significant reduction number hospital days 1 year M-ECT compared with before index episode.
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Electroconvulsive Therapy in Depressed Elderly Patients
TABLE 1.
(Continued)
Study Kramer36
Design Chart review
(1999)
Group Size Diagnosis
Age Range (mean)
ECT Schedule (av. freq.) Electrode placement
Outcome Measure Instruments
Outcome
56: 24 MDD 10 D and axis 2 9 BP 3 SP 10 D and PD 26: 17 MDD 8 BP 1 SA
30–84
Flex Bi
Recovery
MDD 75% remained improved.
60–89 (73)
Flex U
Relapse/recurrence Hospital admission
Relapse of 35% in 12 months. Significant higher hospitalizations 12 months prior M-ECT compared with after M-ECT. 5 patients stopped treatment and had poor prognosis: 1 died, 1 chronic hospitalization, 3 rehospitalized. Significant more recurrences and mean weeks in hospital 3 years previous M-ECT compared with under M-ECT. 9% hospitalization in patients who continued M-ECT.
Beale et al.37 (1996)
Case series
Mirchandani et al.38 (1994)
Case series
9: 8 MDD 1 SA
62–85 (76)
Flex U/Bi
Hospital admission Recovery
Lˆ oo 39 (1991)
Case series
7: 5 MDD 1 BP 1 SA
56–86 (75)
Flex —
Hospital admission Instruments: HDRS, BPRS
Jaffe et al.40 (1990)
Case series
27–84 (68)
Flex U
Hospital admission Relapse Instruments: HDRS
Lˆ oo et al.41 (1990)
Case series
(69)
Flex —
Recovery
Thornton et al.42 (1990)
Chart review
32: 27 MDD 3 BP 2 OA 16: 10 MDD 5 BP 1 SA 10: 9 MDD 1 BP
50–74 (62)
Flex (1/4.1w) U
Hospital admission
12 patients improved by M-ECT. 4 patients did not improve by M-ECT. Significant less hospitalization 18 months after initiating M-ECT than during 18 months preceding.
Notes: Therapy—C-Pharm, continuation pharmacotherapy; C-Therapy: continuation therapy; M-ECT, maintenance electroconvulsive therapy. Diagnosis—BP: bipolar disorder; D: depressive disorder; MDD: major depressive disorder; OA: organic affective disorder; PD: Parkinson disease; SA: schizoaffective disorder; SP: schizophrenia. ECT schedule—Fix: fixed schedule; Flex: flexible schedule; W: week(s), by example: 1/2w is every 2 weeks a M-ECT session; M: month; N: number of M-ECT treatments in fixed schedule; (av. freq.): average frequency M-ECT treatment in flexible schedule. Electrode placement—U: unilateral; Bi: bilateral (bitemporal); —: no information. Instruments—GAF: global assessment of functioning; CGI-S, clinical global impression; HDRS/HAM-D, Hamilton Depression Rating Scale; MADRS, Montgomery-Asberg Depression Rating Scale; (M)MDE, (mini) mental state examination; mMMSE, modified mini mental state examination.
multicenter study from the Consortium for Research in ECT (CORE). After a course of ECT, 184 remitters of a unipolar depression were randomized to either M-ECT without psychotropic medication, or to C-Pharm. Pharmacotherapy consisted of lithium carbonate plus nortriptyline. All ages from 18 to 85 years old were enrolled, and the mean age was 57.1 ± 16.1 years. The primary outcome measure was
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relapse of depression rated by the 24-item Hamilton Depression Rating Scale (HDRS). After 6 months, 37% of M-ECT group relapsed, compared with 32% of the C-Pharm group, not a statistically significant difference (χ 2 = 1.05; p = 0.59). Neither was a statistically significant advantage present for M-ECT for time of relapse, 9.1 ± 7.0 weeks compared with 6.7 ± 4.6 weeks for the C-Pharm (HR = 1.2, 95% CI: 0.7–1.9).
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van Schaik et al. From the CORE study, it can be concluded that, irrespective of which form of maintenance treatment is used, relapse rates after an ECT course are very high and consistent with the results found in the study of Sackeim et al.5 The strengths of this study are the large intention-to-treat sample of 184 patients and the rigorous design for randomization and administrating ECT. Although the vast majority of relapse after successful ECT occurs within the first 4 months,5 one could argue that a 6-month period for follow-up is relatively short. Prospective Studies Five prospective studies met all inclusion criteria for this review. In a naturalistic follow-up study by Wijkstra et al.,24 pharmacotherapy-resistant unipolar depressed patients, who had responded well to ECT, were treated with M-ECT only. The relapse rate was 50% in 6 months (95% CI: 21–79). Relapse was defined as a depressive episode according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, a HDRS score of at least 14 and HDRS scores 50% or more of the baseline score before ECT. Six geriatric patients in a case series by Sigler et al.25 received M-ECT once a month, during at least 6 months. They were all refractory to pharmacotherapy and had on average four relapses before M-ECT was administered. In 6 months, no relapse occurred, as measured by HDRS. Vanelle et al.26 studied patients with unipolar or bipolar disorders for an average of 18 months. Most patients had somatic comorbidity and a long duration of illness. The mean duration of illness was 26 years. They all suffered from pharmacotherapyresistant depression with at least two tricyclic antidepressants and a mood stabilizer or presented contraindications prohibiting pharmacotherapy. In 1 year prior to M-ECT, patients spent on average 44% of the year in the hospital with at least three episodes a year. During M-ECT, 7% of the year was spent in hospital (p <0.001) with less than one relapse every 16 months requiring admission (p <0.001). Among the patients with a major depression, only 60% were in full or partial remission. There was a tendency for a better response in persons with mood disorders with psychotic features. Besides, 45% of patients had a period with more frequent ECT sessions because of worsening in condition.
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In a case series of Thienhaus et al.27 six patients with a very long duration of illness, averaging 22 years, were followed from 1 to 6 years. Four of six patients had a decrease in frequency and duration of hospital admission and improved on all rating scales for depression, cognition, and functional impairment after applying M-ECT. The decline in average annual inpatients days was significant. Clarke et al.28 described a study of patients who received M-ECT without medication. Eight percent of the M-ECT completers relapsed and needed hospitalization, compared with 47% of the patients who failed to complete the protocol (p = 0.04). It was not reported why patients did not complete the protocol. Stopping M-ECT can be a result of relapse and secondary lack of motivation or side effects. Retrospective Studies With Matched Comparison Group Three retrospective studies with a matched comparison group were found. Gupta et al.29 studied patients who proceeded to M-ECT after a positive response on index ECT, compared with a comparison group, matched for sex, age, diagnosis, and time of index ECT. The patients in the comparison group were offered “treatment as usual” after index ECT. The hospital admission rates and bed occupancy did not differ between the two groups. In the M-ECT group, the mean hospital admission rate reduced significantly during the period of M-ECT, compared with the period before the initiation of M-ECT: 1.00 admissions a year compared with 0.316 admissions a year (p <0.001). The bed occupancy was lower in the M-ECT group during treatment (7.05 weeks/year) than in pre-M-ECT (14.05 weeks/year) (p = 0.055). Gagn´e et al.30 reported about patients on M-ECT with pharmacotherapy. The comparison group consisted of patients who received C-Pharm after index ECT, matched on age, gender, diagnosis, age of onset, comorbid psychosis, and year of index ECT course. The mean duration of follow-up was 5.4 years for the M-ECT group. After 2 years, the cumulative probability of remission was 93% in M-ECT compared with 52% in the comparison group. After 5 years, 73% of M-ECT patients had no relapse in contrast with 18% of the comparison group (χ 2 = 19.87, p <0.0001). The mean illness-free time was 6.9 (95% CI: 5.1–8.0) years for M-ECT compared with 2.7 (95% CI: 1.7–3.6) years
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Electroconvulsive Therapy in Depressed Elderly Patients for C-Pharm. Frequency of hospitalization or number of hospital days did not differ between groups. Strengths of this study are the carefully matched comparison group, the long follow-up period, and the use of a structured M-ECT schedule. Schwartz et al.31 studied M-ECT in patients and two comparison groups that were matched on sex, race, diagnosis, and date of admission. The first comparison group consisted of depressed patients who recovered with only pharmacotherapy. The second comparison group received alternative treatment after a successful course of ECT. The rate of rehospitalization of patients receiving M-ECT compared with the period before index episode was significantly reduced by 67% (p ≤0.05). More M-ECT patients than the first comparison group were rehospitalized during follow up, 71% versus 45% (χ 2 = 6.15, p ≤0.05). The second comparison group did not differ significantly in hospitalization compared with M-ECT, but relapsed sooner, 8 versus 16 months (H = 13.7, p <0.05). A major problem in this study is that the patient groups are difficult to compare. Retrospective Studies Without Comparison Group Eleven studies were found. O’Connor et al.32 reports of 53 patients of three geriatric psychiatric services. They received M-ECT on one or more occasions, with a mean of 15 treatments. In the 2 years after the M-ECT started, the number of hospital admissions significantly fell down by 53% in number and 79% in duration, compared with the previous 2 years. The study of Odeberg et al.33 was a chart review of patients who received M-ECT and pharmacotherapy for more than 4 months. M-ECT was individually tapered. The need for hospital care 3 years before and 3 years after M-ECT were compared. The total number of hospital days was reduced by 76% (p <0.001). Also the number of patients hospitalized and the number of admissions in hospital both were significantly reduced by 64% (p <0.0001). Major limitations in this study are incomplete hospital records, lacking instruments to measure relapse, and change of medication and frequency of ECT during the study. Lim34 described an audit of patients receiving M-ECT with a duration range of 3 to 60 months. Patient selection is somewhat unusual, because 29% patients received ECT involuntarily. A comparison
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was made of clinical outcome measures for an equivalent period of time before and after M-ECT. The number of admissions to hospital and length of stay in the hospital following the M-ECT were lower than those before the start of M-ECT (p <0.015) (p <0.010). In a chart review by Russell et al.,35 43 patients received M-ECT for more than a year. The result was a significant decrease in the number of hospital days from 18.95 days to 3.23 days per patient per year (p <0.001). The Global Assessment of Functioning significantly improved after M-ECT, 48.0 versus 55.51 (p = 0.012). Also, HDRS generally improved after starting M-ECT, 29.1 versus 6.1 (p <0.001), but was available for only 11 patients and measured the period before index episode and after 1-year M-ECT. Kramer36 reviewed patient charts during 4.5 years of a university ECT service. Patients with a major depressive disorder benefited from M-ECT, 75% remained free of relapse or recurrence measured by clinical assessment. Information of 1-year follow up in a M-ECT clinic by Beale et al.37 showed 4% relapse after 3 months, 25% at 6 months, and 35% at 12 months using survival analyses. There was a significant decrease in the mean number of hospitalization 12 months prior to M-ECT, 1.8 hospitalization per patient, compared with 12 months following initiation of M-ECT, 0.23 hospitalization per patient (p = 0.0001). Mirchandani et al.38 described 9 geriatric patients referred for M-ECT. Four patients who complied with M-ECT remained well during followup until 1 year. The 5 patients who stopped treatment ˆ et al.39 described a group had negative outcomes. Loo of patients who received M-ECT for nearly 3 years. All patients had significantly fewer hospitalization and recurrences during M-ECT compared with the previous 3 years. In an outpatient ECT clinic, Jaffe et al.40 found that two-third of the patients continued the ECT treatment without requiring hospitalization or had been successfully discharged from treatment. ˆ et al.41 12 of 16 patients with In a case series of Loo a therapy-resistant depression improved by M-ECT according to the clinician. Thornton et al.42 identified 10 patients treated with M-ECT in a university-based ECT service. Most of the patients were suffering from a psychotic depression. There were fewer hospital admissions in the 18 months after initializing M-ECT, with a mean of 0.3 compared with a mean of 3.1 hospital admissions in the 18 months preceding M-ECT (p <0.001).
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van Schaik et al.
SAFETY OF M-ECT Cognition Cognitive problems are an important side effect of M-ECT. Because cognitive decline is associated with aging and with age-related diseases, older people may be more vulnerable to cognitive impairment. Seven studies measured cognitive functioning before and after M-ECT but only with global screening instruments like the Mini-Mental State Examination (MMSE) or the Mental State Examination (MSE). None of these studies reported cognitive problems. In the study of Kellner and colleagues,21 the secondary outcome was cognitive functioning, measured by the modified MMSE (mMMSE), a more expanded instrument compared with the MMSE. Mean scores did not differ significantly at the end of the study (C-Pharm: 49.1 ± 0.5; M-ECT: 48.4 ± 0.5). The mMMSE score improved for both groups during 6 months. A review on the effects of ECT on cognitive functioning in the elderly patients gave information of cognitive effects during M-ECT on the basis of three studies. Global cognitive functioning, as measured with the MMSE, remained stable after receiving M-ECT over at least a year, whereas learning verbal information and executive functioning was impaired, compared to a group of matched patients who had never received ECT.43 Recently, data from the CORE study were published in which memory effects of M-ECT versus C-Pharm were compared at 12 and 24 weeks to baseline in 85 patients who completed the course without relapse.44 At 12 weeks, patients on M-ECT had lower scores on a retrograde memory test compared to C-Pharm (p <.01), but after 24 weeks these differences disappeared.
Physical Comorbidity Although several studies included a large group of patients with somatic comorbidity such as cardiac or neurological conditions, M-ECT was generally well tolerated because none of them caused significant morbidity or interfered with further ECT.26,32,35,38, 40–42 Falls, delirium and cardiac problems were described in the studies of Russell et al.,35 Jaffe et al.,40 and Vanelle et al.26 as temporary physical reactions to ECT.
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In the three randomized trials, all patients with central nervous system disease and somatic conditions complicating therapy were excluded. In the studies of Navarro et al.22 and Serra et al.,23 changes of diastolic and systolic blood pressure, electrocardiographic intervals, and heart rate were measured. Side effects were assessed by the Udvalg for Kliniske Undersogelse Side-Effect Rating Scale. Both treatments, M-ECT with nortriptyline and nortriptyline as C-Pharm, were well tolerated. No significant differences in Udvalg for Kliniske Undersogelse scores, or changes in electrocardiographic intervals, heart rate, or blood pressure were found. In the study of Kellner and colleagues,21 adverse effects were noted. Two patients from the M-ECT group, who dropped out of the study, complained of memory loss and headache, whereas 13 patients who received C-Pharm stopped because of adverse reactions to medication.
DISCUSSION Although research on this clinically important topic is sparse, we were able to select 22 studies meeting inclusion criteria. The majority was published recently, reflecting a growing interest of clinicians in MECT. To date, only 3 randomized controlled trials were performed, whereas this method is considered the best way to study the effectiveness of treatment. From these studies, one might conclude that M-ECT has a comparable efficacy as C-Pharm in the prevention of relapse or recurrence of a depressive episode. The study of Navarro et al.,22 however, yielded better outcome during the first months than the CORE study and continued to do so during the 2 years of M-ECT. These differences can neither be explained by patient selection in the Navarro-trial (psychotic depression and an age above 60 years) because adjustment for the covariables psychosis and age did not change the effect significantly in the CORE study, nor by the ECT procedures, because in both studies bilateral treatment and a fixed MECT schedule were applied. A possible explanation for the better results of M-ECT by Navarro et al.22 could be the additional pharmacotherapy with nortriptyline.45 The notion that M-ECT with addition of nortriptyline was well tolerated in this geriatric population is comforting. In the study of Navarro et al.22 and Serra et al.,23 a shorter time until
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Electroconvulsive Therapy in Depressed Elderly Patients relapse was found for the C-Pharm group compared to the M-ECT group; the same trend was seen in the CORE study, although it did not reach significance (p = 0.13). The five prospective studies are difficult to compare because they use different methods for patient selection, depression measurements, length of treatment, pharmacotherapy, and ECT-procedures. The majority of patients were medication-resistant.24–26,28 The relapse rate of patients with medication-resistant depression with M-ECT of 50% in the Wijkstra et al.24 study did not differ from the results of the CORE study. A cautious conclusion from these studies is that M-ECT could also be effective in medicationresistant elderly patients or in elderly patients with a long illness duration. M-ECT was especially profitable in terms of hospitalization compared with the period before M-ECT. Three retrospective studies with matched comparison groups describe their M-ECT population as more severely ill, with a larger number of admissions, more psychotropic medication, or more previous ECT. Despite careful matching, selection bias seems thus inevitable. All studies show a significant decrease of hospitalization after starting M-ECT compared with earlier periods. Significant differences in hospitalization or relapse of M-ECT compared with matched patients, however, could not be demonstrated. Eleven retrospective studies without matched comparison groups were found, all with severe methodological limitations. Despite the referral of more severely and chronically ill patients to M-ECT, all studies showed improvement after M-ECT, measured by hospital admission or clinical outcome. Considering efficacy, from the three randomized trials,21–23 it can be concluded that M-ECT and C-Pharm have comparable efficacy. The clinician should note, however, that this can only be concluded for M-ECT using a fixed treatment schedule. It is very well possible that RCTs using a fixed schedule underestimate the effectiveness of M-ECT. In clinical practice, treatment frequency is commonly increased when the patient shows signs of relapse. It seems reasonable to assume that patients might benefit from an individual approach when the intertreatment interval based on (early) signs of relapse is flexible. In most of the prospective and retrospective studies,28,36,37,40 this flexible approach was used, yielding impressive results. Nevertheless, from the current randomized
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evidence, the superiority of M-ECT cannot be concluded. After a successful ECT course, therefore, CPharm should be continued for relapse prevention. Should C-Pharm fail, M-ECT is to be considered. A limitation of a review on this topic is the lack of well-controlled studies, not allowing a meta analysis of randomized evidence. We chose to study all relevant studies on this subject and included studies with different methodology, sample size, and patient selection like age and sample size, hampering comparison between studies and firm conclusions, but providing a fair overview of the efficacy and safety of M-ECT for these patients. Publication bias may have lead to a more favorable view on the efficacy of M-ECT in this review, particularly due to the noncontrolled studies. Nevertheless, naturalistic studies were also included despite their severe methodological limitations, as open prospective and retrospective studies may represent daily practice reasonably well. Performing an RCT with elderly depressed patients after an index episode of ECT is met by special difficulties as costs, number of subjects that should be enrolled and the issue of comorbidity. For elderly patients with medical comorbidity and comedication, randomization is often very difficult. Finally, choosing a relative low mean age of 55 years and older, limits the generalizability of our findings to the oldest old. The same applies to safety aspects especially in the oldest old who may be more at risk for cardiovascular complications and cognitive impairment. Cognitive functioning, an important clinical issue geriatric depression, has not been studied properly to date. In two studies, no significant differences were found between cognitive functioning of patients treated with M-ECT and control patients treated with M-Pharm after index ECT, but neither long-term effects were studied nor older old patients.44,46 Despite the common physical comorbidity, M-ECT was generally well tolerated with only rare physical complications indicating the relative safety of this treatment modality. According to our findings, the discouragement by the National Institute for Clinical Excellence to practice M-ECT, because evidence is lacking for long-term benefits and because of potential risks of M-ECT, is too conservative.47 The notion of the American Psychiatric Association task force that M-ECT should be available in centers practicing ECT is supported by our study and more in line with clinical
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van Schaik et al. practice.6 But then, again the suggestion that M-ECT should be offered as a standard of care after an index episode of depression treated with ECT as an alternative for medication in depressed elderly patients was also not supported by our study. For clinicians, it is important that M-ECT is available when treating severely depressed elderly patients after improvement with index ECT in case of prior relapse while on adequate C-Pharm, in case of medication intolerance, or patient’s preference.17,48,49 This review gives rise to several questions and topics for further research on M-ECT. Which M-ECT technique and procedure is most effective in preventing the relapse or recurrence of a depressive disorder after successful ECT? As discussed earlier, more research is needed as to which treatment schedule, fixed or flexible, is superior. To our knowledge, studies examining this issue are ongoing.50,51 The three RCTs used bilateral placement and all studies published in the last 10 years used bilateral placement or a combination. Although bilateral placement is considered more effective in acute ECT, whether this applies for M-ECT, remains elusive.2,52 In different studies, different placements were used, but no study has compared electrode placements during M-ECT. Although a recent CORE-trial, comparing bitemporal, bifrontal, and unilateral ECT, failed to show significant differences between the three techniques, it is conceivable that during M-ECT the electrode placement used, in combination with stimulus dose and stimulus parameters, may have effects on treatment efficacy and, perhaps even more, on cognitive side effects.52 Because bilateral treatment might confer a greater risk of cognitive impairments,
especially relevant in old age, many geriatric psychiatrists prefer unilateral placement currently.53,54 Another question is whether M-ECT should be combined with additional continuation pharmacotherapy. The study of Navarro et al.22 suggests that M-ECT with nortriptyline might provide better prevention of relapse. In a recent study of Sackeim et al.,45 concomitant pharmacotherapy was given during an ECT course. Addition of nortriptyline enhanced the efficacy with a 15% increase in remission rate and reduced the cognitive side effects, with respect to placebo. Furthermore, little is known about which clinical characteristics predict a positive response on M-ECT. From the selected studies, old age, psychotic symptoms, medication resistance, or physical illness did not predict negative response on M-ECT treatment. In addition, patient and family perspective and compliance should be studied more with regard to M-ECT.55 Patients’ dislike of the treatment or preference, logistic problems when living at home or in a institutional setting, social support, and the required repeated anesthesia are worth mentioning. Evaluation of M-ECT programs in this respect are lacking. Finally, more information about cost-effectiveness of M-ECT is needed. In a cost utility analysis by Aziz et al.,56 the costs and outcomes of M-ECT differed favorably from those of C-Pharm in a theoretical cohort of elderly patients with a recurrent major depressive disorder. In conclusion, this review summarizes the available research of M-ECT in geriatric depression. According to our results, M-ECT can be an important treatment option for relapse prevention in severely depressed elderly patients.
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