Electroconvulsive therapy (ECT) is the longest standing psychiatric treatment available and has unequivocal benefit in severe depression. However this treatment comes with a number of side effects such as memory impairment. On the other hand, Repetitive Transcranial Magnetic Stimulation (rTMS) is a relatively new form of treatment which has been shown to be efficacious in patients suffering from a number of psychopathologies, including severe depression, with few reported side effects. Due to its potential therapeutic efficacy and lack of side effects, rTMS has gained traction in the treatment of depression, with a number of authors keen to see it take over from ECT. However, it is not clear whether rTMS represents a therapeutic alternative to ECT. This meta-analysis will therefore compare the “gold standard” treatment for severe depression, with the relatively new but promising rTMS. A literature search will be performed with the intention to include all randomised clinical trials. The null hypothesis is that there is no difference in the antidepressant efficacy between the two types of treatment modalities. Statistical analysis of Hamilton Depression Rating Scale (HDRS) scores will be performed.
ECT is one of the oldest forms of treatment in psychiatry that is still used today. A recent systematic review showed “
A British Journal of Psychiatry systematic review [
One advantage of rTMS over ECT is that the patient does not need anaesthesia, as well as the fact that seizures need not be induced. Therefore, rTMS has a much safer risk profile compared to ECT. Common side effects of rTMS are headache, twitching of the facial muscles, and auditory impairments, during the actual treatment. With respect to severe acute adverse effects, induction of seizures, though rare, has been known to occur. In the early days of rTMS accidental seizures were reported and thought to be caused by overstepping of safety limits now in place. However, in their report on the safety of rTMS, Rossi et al. conclude that the risk of rTMS to induce seizures is very low, taking into account the large amount of study data that exists from 1998 [
This meta-analysis sets out to compare ECT to the relatively new but promising rTMS, for the management of treatment resistant depression. The null hypothesis being tested is that there is no statistically significant difference in the antidepressant efficacy between the two types of treatment modalities.
A literature search was carried out with OvidSP using the following resources: MEDLINE (1996 to January Week 5 2013), EBM Reviews—Cochrane Database of Systematic Reviews (2005 to January 2013), EBM Reviews—ACP Journal Club (1991 to January 2013), EBM Reviews—Cochrane Central Register of Controlled Trials (1991–January 2013), Embase (1974 to 2013 Week 06), and PsycINFO (1806 to February Week 1 2013). Search was carried out with a
To be included in the meta-analysis the clinical trial should (1) compare the effect of ECT and rTMS in the treatment of depression, (2) be a randomised clinical trial (RCT) published in an English journal, (3) be conducted on human subjects who are over the age of 18 and have given informed consent, (4) be prospective with parallel design, (5) meet ICD-10 or DSM-IV criteria for unipolar depression or bipolar depression with a current depressive episode, (6) have HDRS assessed shortly before and after treatment, and (7) report HDRS score and standard deviation (SD). A single exclusion criterion was used: comorbid drug abuse.
Each study was meticulously examined and evaluated for study quality. The quality of the existing literature was judged using Chalmer’s method [
After the completion of the database search, the articles were read carefully and a brief summary of each article was written. The studies were then tabulated under the following headings: authors, the year of publication, the number of participants, rTMS or ECT, gender, psychotropic drugs, the type of rTMS technology used, the type of ECT technology used, and the HDRS mean and standard deviation before and after treatment in both groups.
Statistical analyses were done with SPSS (IBM) and Comprehensive Meta-Analysis software (Biostat). Changes in HDRS scores in participants were analysed using paired and independent
The meta-analysis included 9 randomised clinical trials published between 2000 and 2011 with a total of 384 participants. Table
Patient characteristics and treatment protocols.
Study |
|
Age | Episode duration (mo) | Treatment protocol | Diagnosis | |||
---|---|---|---|---|---|---|---|---|
rTMS | ECT | rTMS | ECT | rTMS | ECT | |||
Keshtkar 2011 [ |
73 | 34.0 | 35.6 | n.a. | n.a. | MS: 10 |
MS: 10 |
UP |
Hansen et al. 2011 [ |
60 | 46.0 | 52.0 | 6.0 | 4.0 | MS: 15 |
MS: 9 |
UP + BP |
Eranti 2007 [ |
46 | 63.6 | 68.3 | 7.1 | 5.6 | MS: 15 |
MS: 6.3 |
UP |
Rosa et al. 2006 [ |
42 | 41.8 | 46.0 | 110.7 | 103.6 | MS: 20 |
MS: 12 |
UP |
Schulze-Rauschenbach et al. 2005 [ |
30 | 47.7 | 46.7 | n.a. | n.a. | MS: 10.8 |
MS: 9.9 |
UP |
O'Connor et al. 2003 [ |
28 | 51.2 | 48.4 | n.a. | n.a. | MS: 10 |
MS: 6–12 |
n.a. |
Grunhaus et al. 2003 [ |
40 | 57.6 | 61.4 | 16.6 | 10.4 | MS: 20 |
MS: 10 |
UP |
Janicak et al. 2002 [ |
25 | 42.9 | 42.7 | 5.5 | 3.1 | MS: 20 |
MS: 12 |
UP + BP |
Grunhaus et al. 2000 [ |
40 | 58.4 | 63.6 | 8.3 | 6.9 | MS: 20 |
MS: 9.6 |
n.a. |
Notes
ECT patients varied with respect to their psychopharmacological treatment, with two studies requiring that patients be off treatment before commencement of the study [
The average improvement in HDRS scores for both groups was substantial. The participants who underwent rTMS had a mean reduction of 9.3 points on the HDRS (SD 4.45, SE 1.48) which was found to be significant with
A two sample
Bias Corrected (Hedges) Effect Sizes was calculated in the 9 studies, for both rTMS and ECT. Effect sizes ranged from 0.56 to 2.83. The mean effect size for rTMS was 1.33 whilst that for ECT was 2.14. Table
Bias corrected (Hedges) effect sizes for each study.
rTMS | ECT | |||||||
---|---|---|---|---|---|---|---|---|
Study | Confidence interval | Confidence interval | ||||||
Effect size | Standard error | Lower | Upper | Effect size | Standard error | Lower | Upper | |
Keshtkar 2011 [ |
|
0.26 | 0.39 | 1.40 |
|
0.32 | 2.21 | 3.44 |
Hansen et al. 2011 [ |
|
0.28 | 0.75 | 1.87 |
|
0.32 | 1.45 | 2.70 |
Eranti 2007 [ |
|
0.30 | 0.16 | 1.33 |
|
0.43 | 1.99 | 3.66 |
Rosa et al. 2006 [ |
|
0.36 | 0.89 | 2.32 |
|
0.42 | 0.74 | 2.38 |
Schulze-Rauschenbach et al. 2005 [ |
|
0.43 | 1.07 | 2.73 |
|
0.44 | 0.81 | 2.53 |
O'Connor et al. 2003 [ |
|
0.39 | −0.20 | 1.31 |
|
0.48 | 1.32 | 3.22 |
Grunhaus et al. 2003 [ |
|
0.36 | 0.83 | 2.25 |
|
0.38 | 1.18 | 2.68 |
Janicak et al. 2002 [ |
|
0.47 | 1.00 | 2.86 |
|
0.59 | 1.00 | 3.33 |
Grunhaus et al. 2000 [ |
|
0.36 | 0.79 | 2.19 |
|
0.38 | 1.16 | 2.65 |
A two sample
The The Radial Plot can be seen in Figure
Radial Plot rTMS.
Homogeneity analysis showed significant heterogeneity in the combined effect sizes for the rTMS studies; therefore, additional analysis was performed. An investigation was carried out to check out the validity of the data from the studies. However, no obvious reason for heterogeneity was found, and a decision was made to proceed with the Random Effect Model for combined Effect Size analysis. A forest plot can be seen in Figure
Forrest Plot rTMS.
The The Radial Plot can be seen in Figure
Radial Plot ECT.
Homogeneity analysis showed no significant heterogeneity in the combined effect sizes for the ECT studies; therefore, not any additional analysis was performed. Forest plot can be seen in Figure
Forrest Plot ECT.
Combined effect sizes for Fixed and Random Effect Models can be seen in Table
Combined effect sizes for fixed and random effect models.
rTMS | ECT | |||||||
---|---|---|---|---|---|---|---|---|
Model | Confidence interval | Confidence interval | ||||||
Effect size | Standard error | Lower | Upper | Effect size | Standard error | Lower | Upper | |
Fixed effect | 1.24 | 0.11 | 1.01 | 1.46 |
|
|
|
|
Random effect |
|
|
|
|
2.15 | 0.16 | 1.85 | 2.46 |
Tolerance minimum number = 55. Estimated number = 282. Estimated not less than minimum: publication bias not detected.
Publication Bias for ECT Studies.
Tolerance minimum number = 55. Estimated number = 587. Estimated not less than minimum: publication bias not detected.
To my knowledge, this is the first meta-analysis that set out to analyse and compare ECT, the “gold standard” treatment for severe depression, with the relatively new but promising rTMS. Following extensive literature review, nine randomised controlled clinical trials were included. The null hypothesis, that is, that there is no significant difference in the antidepressant efficacy between the two types of treatment modalities, was tested using a number of statistical measures and was refuted.
The results of this meta-analysis show that patients who undergo either rTMS or ECT have statistically significant reductions in their depressive symptoms, as measured by HDRS. rTMS participants had a mean reduction of 9.3 points whilst ECT participants had a mean reduction of 15.42 points on the HDRS. This is an important conclusion, especially when one takes into account the fact that the majority of participants who were referred for the studies were refractory to treatment with psychotropic medication. When the degree of improvement between rTMS and ECT participants was analysed, those participants undergoing ECT showed significantly lower HDRS scores compared to those undergoing rTMS. When the effect size was factored into the comparison, the difference became even more significant in favour of ECT. This conclusion reaffirms ECT as the leading therapeutic modality for patients with treatment resistant depression, purely on the basis of depressive symptomatology outcome, but also suggests the therapeutic validity of rTMS as a treatment tool for depression in patients who are treatment resistant.
Three of the nine studies concluded that the antidepressant effect of ECT is significantly larger than rTMS when the groups were compared (Eranti et al., 2007) [
Whilst ECT is known to be effective in patients who are in both their depressive as well as their manic phases of their bipolar illness [
One of the main limitations of this meta-analysis, which reflects the limitations of the individual studies, is that placebo/sham groups were not used; although the studies were randomised and controlled, a sham comparison group was not used. As described by Grunhaus, this lack of control may constitute a problem in both rTMS as well as ECT groups:
Another important consideration which must be taken into account is that the studies were not blinded, both with respect to observers as well as to participants. In fact, only one of the studies was single blind with respect to observers [
In three of the studies [
In some of the studies ECT was continued until treatment response, while rTMS was administered over a predetermined schedule. As suggested by Eranti et al. (2007)
One of the main outcomes of the included studies was response and remission according to HDRS scale. Response is commonly defined as a reduction in HDRS score of 50% or more whilst remission as a final HDRS score of eight or less [
As previously discussed, treatment resistance generally occurs when there is inadequate response to at least two antidepressants [
As previously discussed, study participants differed with respect to age and sex distribution, drug therapy, type of depression, psychotic symptoms, treatment parameters, and blinding. Nevertheless, all studies reported initial and endpoint HDRS scores, which was one of the main criteria for admission of the study into the meta-analysis. In addition to the limitations described above, the main limitations of the meta-analysis were that the studies that have been carried out (and included in this meta-analysis) comparing rTMS and ECT are small, with a limited number of participants (between 25 and 73) which makes generalisation of results difficult. The main reason for this is that rTMS is still in its infancy when it comes to routine clinical use, and in many places it remains an experimental technique. As the use of rTMS gains traction, further studies, with larger sample populations, will allow further investigation of the benefits of rTMS, and therefore a better comparison with ECT can take place.
Another limitation to consider is the use of the HDRS. A number of studies have criticised the scale’s ability to measure the severity of the patient’s depression and have concluded that the scale suffers from poor retest and inter-rater reliability, poor content validity, as well as poor replication across samples [
As a result of the limitations listed above, a number of improvements should be sought in future meta-analyses. However, since many of the limitations are due to the design of the studies themselves, this will add a degree of difficulty for subsequent meta-analyses to overcome. Future work on the effects of patient age and diagnosis of unipolar versus bipolar depression, when comparing the two treatment modalities, would help to shed further light onto the significant difference found in this meta-analysis. Comparison of the short term and long term side effects would also be an essential step in the risk/benefit analysis of the two treatment modalities, allowing clinicians to select the most appropriate modality for particular patients.
In conclusion, this report comparing the effects of rTMS and ECT in the treatment of depression, whilst showing ECT’s superiority when compared directly to rTMS, also shows that rTMS can be considered as a useful adjunct to the therapeutic interventions in depression currently available. Whilst not proving beyond reasonable doubt the efficacy of rTMS, this meta-analysis indicates an important role for rTMS in the management of treatment resistant depression, especially in select patient groups. However, the future success and deployment of this treatment modality will largely be contingent upon further technological as well as logistical advances that can help to clarify effective use, cost-effectiveness, access to treatment, and patient selection.
There are no conflict of interests declared by the author.