Department of Pschiatry, University of Bonn, Germany
Correspondence: Dr Michael Wagner, Department of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, D 53105 Bonn, Germany.Tel: +49 228 287 6377; fax: +49 228 287 6371; e-mail: michael.wagner{at}ukb.uni-bonn.de
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Aims To compare the neurocognitive effects of unilateral ECTand rTMS.
Method Thirty patients with treatment-refractory non-psychotic major depression received an average of ten treatments with either unilateral ECT or left prefrontal rTMS and were assessed for objective and subjective cognitive impairments before and about a week after treatment.
Results Treatment response was comparable (46% of the ECT group and 44% of the rTMS group showed a reduction of 50% or more in Hamilton Rating Scale for Depression scores). In patients treated with rTMS, cognitive performance remained constant or improved and memory complaints alleviated, whereas in the ECT group memory recall deficits emerged and memory complaints remained.
Conclusions In contrastto unilateral ECT, rTMS has no adverse memory effects.
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In weighing the benefits and risks of different treatment methods, cognitive side-effects are an important issue. Electroconvulsive therapy has been shown to induce anterograde amnesia, retrograde amnesia and subjective memory complaints (e.g. Squire & Slater, 1983; Lisanby et al, 2000). Although such deficits tend to cease within weeks to months, a review of patients perspectives on ECT (Rose et al, 2003) indicates that persistent memory impairment following this therapy may be more frequent than is evident from testing with standard neuropsychological batteries. In contrast, rTMS seems not to have any substantial cognitive side-effects (e.g. Triggs et al, 1999). However, a comprehensive comparison of cognitive side-effects is lacking so far.
![]() |
METHOD |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The patient sample consisted of 16 men and 14 women; the average age was 47 years (range 2569) (Table 1).
|
All patients were referred for ECT or rTMS at the University Hospital of Bonn after prior treatments with antidepressant drugs had failed. The department offers both of these therapies, and is one of only a few specialised treatment centres in Germany to do so. All participants approached our clinic with the specific wishor a referring doctors recommendation to receive either rTMS or ECT, and received the treatment of their choice if no clinical exclusion criterion was present. The study consisted of consecutively admitted cases within a specified period, going into either the rTMS or the ECT group with comparable likelihood. Fourteen patients were treated with ECT and 16 received rTMS. The two groups did not show significant differences on any of the variables measured; most importantly, they were comparable with regard to age, gender, level of depression, level of education and verbal IQ (Table 1). Furthermore, the cognitive status levels of the two groups at baseline were almost identical, allowing us to study the changes induced by ECT or rTMS. All participants participants gave informed consent to repeated neurocognitive assessment.
In order to disentangle treatment-related changes in performance from test repetition effects, a control group of 15 healthy volunteers, matched by age, gender, level of education and verbal IQ to the patient groups (see Table 1), was also assessed twice, with the same interval between testings as the patients.
Clinical ratings and neuropsychological tasks
Patients and controls were assessed with an extensive test battery before
and about a week after completion of the treatment. Pre-treatment testing took
place 13 days before the first treatment session, and the
post-treatment testing was done 8.8 days on average after the last ECT or rTMS
session with equal intervals between the last treatment and post-treatment
testing for both groups (P=0.68, NS). The clinical effects of ECT and
rTMS were assessed using the 17-item Hamilton Rating Scale for Depression
(HRSD; Hamilton, 1967; German
version by the Collegium Internationale
Psychiatriae Scalarum, 1978) and the Beck Depression Inventory
(BDI; Beck et al,
1961; German version by
Hautzinger et al,
1994). The ratings were made by the treating clinical
psychiatrist. Cognitive effects of ECT and rTMS were assessed with a
comprehensive neuro-psychological battery (see Appendix) with special emphasis
on memory functions. Cognitive testing was done by a psychologist masked to
the treatment assignments.
Treatments
Electroconvulsive therapy
Electroconvulsive therapy was given in accordance with current clinical
guidelines (American Psychiatric
Association, 1990; Folkerts,
1997), using a Thymatron III DG stimulator (Somatics Inc.,
Illinois, USA), which delivers a brief-pulse bi-directional current. All
treatments were given under anaesthesia with propofol (2 mg/kg), muscle
relaxation with suxamethonium (1 mg/kg) and 100% oxygenation. Medication was
not changed during treatment. Antidepressants, low-potency neuroleptics and
non-benzodiazepine hypnotics were allowed. Stimulation was always unilateral
on the right hemisphere (all patients were reported to be right-handed for
several manual activities). Seizure threshold was determined by a titration
method and was age-based. Stimulation intensity was 22.5 times the
seizure threshold. Therapy was given twice-weekly with a minimum interval of
48 h between treatments. Decisions concerning the number of treatments were
made by the psychiatrist in attendance; participants received a mean of 9.9
(s.d.=2.7) treatments.
Transcranial magnetic stimulation
Transcranial magnetic stimulation was given with a Magstim Rapid machine
(Magstim Co. Ltd, Whitland, UK). To make the frequencies of ECT and rTMS
comparable, patients were treated two or three times per week; they received a
mean of 10.8 (s.d.=1.4) treatments. Medication was kept constant as well.
Stimulation was applied over the left dorsolateral prefrontal cortex with an
intensity of 100% and a frequency of 10 Hz (2030 trains of 2 s duration
per treatment session, 5 s intertrain interval). Stimulation frequency was
identical to that in previous studies comparing rTMS and ECT (Grunhaus et
al, 2000,
2003;
Janicak et al,
2002).
Data analysis
Data analysis was done using the Statistical Package for the Social
Sciences, for Windows version 10.0. To compare the two treatment methods,
analyses of variance (ANOVAs) with repeated-measures, between-group
t-tests (Welch-corrected for unequal variances) and within-group
t-tests were performed. In addition, the numbers of responders in
both groups were compared using a chi-squared test. Patients were considered
to be responders to treatment if their HRSD scores had decreased by at least
50% from baseline levels. One person in the ECT group withdrew from the study
because of severe orientation and memory problems after two ECT treatments;
these data were not included in the analysis.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Patients were considered to be responders to treatment if their final HRSD
score had decreased by 50% or more from baseline. According to this criterion,
46% of the ECT group and 44% of the rTMS group were treatment responders
(2(1)=0.02, P=0.90, NS).
Neuropsychological effects
Before treatment, the two groups with depressive disorder did not differ
from each other on any of the neuropsychological measures
(Table 2). After treatment,
significant differences between the ECT and rTMS treatment groups emerged for
specific memory functions; these differences were consistently in favour of
rTMS. Significant differences between patient groups after treatment were
found in five measures of long-term memory recall or recognition, but not for
any non-memory measure (Table
2).
|
Anterograde memory function
Significant differences to the disadvantage of ECT were found in two
variables of the Auditory Verbal Learning Test (AVLT;
Rey, 1964): loss after
interference (trial 5 minus trial 6) and loss after delay (trial 5 minus trial
7). In the ANOVA, the group x time interaction was significant for both
measures (F(1,23)=7.81, P=0.010 and
F(1,23)=15.56, P=0.001), whereas the effects of
time and group were not significant (Fig.
2(a)).
|
Retrograde memory function
After treatment, participants in the ECT group made significantly more
errors than those in the rTMS group in recognising words learned before
treatment (P=0.025). After treatment, they also recalled
significantly fewer items from the visual card task administered before
treatment, compared with the rTMS group (P=0.012)
(Fig. 2(b)).
Subjective memory complaints
After treatment, participants given ECT reported no change in memory
problems compared with before treatment (P=0.38, NS), whereas the
rTMS patients judged their own memory much more positively after treatment
(P=0.002). The ANOVA of the subjective memory measure showed a
significant time effect (F(1,23)=11.04, P=0.003)
and a groupxtime interaction approaching significance
(F(1,23)=3.68, P=0.067) in the absence of any
group effect (Fig. 2(c)).
In summary, significant between-group differences were found in anterograde verbal memory, in two retrograde memory parameters and in participants subjective estimation of their own memory abilities. In contrast to memory, other cognitive functions measured remained constant in both treatment groups; we found no significant group, time or interaction effect in these variables (Table 2).
Association of memory and depression
Weiner et al
(1986) found no relationship
between subjective and objective memory measures in patients given ECT, and
concluded that self-rated memory changes may be more a function of clinical
symptoms than of objectively demonstrable changes in memory function. We
explored this issue, correlating the subjective memory complaints, rated with
the Squire Subjective Memory Questionnaire
(Squire et al, 1979),
with the level of depression (BDI and HRSD scores) and with the assessed
neuropsychological variables. The patients memory complaints correlated
with depression as well as with several cognitive measures. The
patients self-ratings of memory functions correlated significantly with
their self-ratings of depression (BDI: r=-0.67, P<0.01),
but less so with the clinician ratings of depression (HRSD: r=-0.31,
P=0.13). Self-rating of memory also correlated with the ability to
learn and recall new verbal and visual material (AVLT sum of trials 15:
r=0.42, P<0.05; AVLT trial 7 after delay:
r=0.46, P<0.05; Memory for Persons Test, delayed recall,
r=0.48, P<0.05), and with the ability to correctly
recognise words learned before treatment (retrograde AVLT, false alarms:
r=0.61, P<0.05), but not with their
autobiographical memory (r=0.07, P=0.75, NS). Importantly,
the correlations between subjective and objective memory did not change
markedly when controlling for self-rated (BDI) depression by partial
correlations.
Comparison with healthy controls
The group of healthy controls was included to control for test repetition
effects and to see whether (and which) impaired cognitive functions would
return to normal levels after treatment in both groups. A comparison of the
cognitive functions of the participants with depression and the healthy
controls at baseline showed highly significant deficits on the part of the
patients in almost all measures. Repeated-measures ANOVAs comparing each
treatment group separately with the healthy control group revealed that the
performance gap between the ECT and control groups with regard to anterograde
memory increased (group time interaction, P<0.05 for recall after
interference and P<0.001 for recall after delay). In contrast, the
difference between the rTMS and control groups remained unchanged (the
groupxtime interactions were not significant).
After treatment, the ECT and control groups differed considerably in their ability to remember words or cards from pre-treatment testing (retrograde AVLT: P=0.049; four-card task: P=0.001), whereas the rTMS group showed retrograde memory functions identical to those of the control group (retrograde AVLT: P=0.33, NS; four-card task: P=0.26, NS). Similarly, the self-rating of memory functions by the rTMS group differed significantly from that in the control group only before treatment (P=0.001); after treatment the rTMS group rated their memory functions to be as good as those of the healthy group (P=0.69, NS). In contrast, the ECT group rated their memory abilities more negatively than the control group both before (P=0.001) and after treatment (P=0.039). The groupxtime interaction in the ANOVA comparing control and rTMS groups was significant (P<0.001), but this interaction was not significant in the ANOVA comparing the control and ECT groups (P=0.30, NS).
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Clinical effectiveness of ECTand rTMS
The two treatments appeared to be clinically equivalent in this group of
patients with treatment-resistant, non-psychotic depression. Although the
study was not randomised, its finding of comparable anti-depressant efficacy
of ECT and rTMS is in line with the results of all three randomised comparison
studies published so far (Grunhaus et al,
2000,
2003;
Janicak et al, 2002).
The rates of those responding to unilateral ECT are in the expected range for
medication-resistant non-psychotic depression
(McCall, 2001), but might have
been higher if a higher ECT dosage had been used
(Sackeim et al,
2000). However, a higher dosage would probably increase the risk
of cognitive adverse effects. A definitive answer to the question of clinical
equipotency of ECT and rTMS will have to await further studies.
Anterograde memory
Patients treated with ECT showed more anterograde memory problems at the
post-treatment assessment than did either patients treated with rTMS or
healthy controls. In particular, they remembered fewer words only after
learning the interference word list of the Auditory Verbal Learning Test
(between Trials 5 and 6 of the AVLT), indicating a recall deficit rather than
a working memory or learning deficit. This extends findings by Hasse-Sander
et al (1998), who
reported impaired verbal delayed recall 12 days after unilateral ECT
(no longer follow-up was made), and of Cronholm & Ottosson
(1961), who described specific
deficits in the delayed recall of newly learned words, figures and persons 1
week after bilateral ECT. For the rTMS group, the lack of anterograde memory
effects is in line with previous studies (e.g.
Triggs et al,
1999).
Retrograde memory
The ECT patients, in contrast to the patients treated with rTMS or the
control group, also showed retrograde memory problems after treatment. They
remembered fewer of the pictures and made more errors in recalling words
learned before treatment. No difference emerged for auto-biographical memory,
which is in line with previous studies demonstrating deficits in recall of
past events only after bilateral ECT, not after unilateral therapy
(Squire et al, 1981;
Weiner et al, 1986;
Lisanby et al, 2000). The verbal and visual retrograde memory tasks used here might be more
sensitive to ECT-induced impairments than the Autobiographical Memory
Interview, possibly because recent memory traces formed during the days before
treatment are more vulnerable to ECT effects than are more remote memories
(Squire et al, 1981;
Lisanby et al,
2000).
Subjective memory
After treatment, the ECT patients complained more about memory problems
than the rTMS patients and the controls. Squire et al
(1979), Freeman et al
(1980) and Squire & Slater
(1983) also found subjective
cognitive side-effects after ECT. After rTMS the patients subjective
memory ratings equalled those of the healthy controls, whereas after ECT the
patients ratings were very negative. This group difference cannot be
explained by different clinical effects of the two treatment methods. At least
in part, this group difference in subjective memory appears to be related to
objectively measurable memory impairments after ECT, because the subjective
memory functions not only correlated with the level of depression, which is a
common finding (e.g. Weiner et
al, 1986), but also with several objective memory measures
(even when statistically controlling for the level of depression).
Associations between subjective and objective memory measures after ECT have
often found to be lacking (e.g. Prudic
et al 2000), but some studies suggest that such a
relationship may exist, at least for certain forms of memory and for specific
periods after ECT (e.g. Freeman et
al, 1980). Thus, complaints of patients about memory deficits
(metamemory) may partly result from the experience of objective memory
failures after ECT, and should not be dismissed as being simply a sign of
depressive complaints.
Clinical implications
With regard to objective and subjective memory function, patients with
severe depression appear to be cognitively better off 1 week after a course of
rTMS than 1 week after a course of unilateral ECT, despite (in this study) an
indistinguishable antidepressive effect of the two treatments. Adverse memory
effects after ECT may fully resolve after a longer interval, usually after
several months (Weeks et al,
1980); nevertheless, if rTMS evolves into an alternative treatment
for some forms of medication-resistant depression, clinicians and patients
should be aware of its reduced risk for adverse memory effects, compared with
unilateral ECT. Future comparison studies of ECT, rTMS and magnetic seizure
therapy (Kosel et al,
2003) should include sensitive memory assessments and longer
follow-up intervals to evaluate fully the ratio of benefits and risks of these
treatment methods.
Limitations
Because our study lacked a sham-treated patient control group and patients
were not randomly assigned to treatments, no conclusion should be drawn
regarding the absolute or relative antidepressant effectiveness of rTMS or
ECT. Although the pattern of cognitive findings, in line with previous work,
suggests that unilateral ECT, in contrast to rTMS, specifically impairs
several aspects of memory for at least a week after a treatment series, the
small number of participants in our study renders this a preliminary finding
requiring confirmation in other samples.
![]() |
APPENDIX |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Retrograde memory function
Subjective memory function
Squire Subjective Memory Questionnaire
(Squire et al, 1979):
this 18-item self-rated scale of memory functions comprises items such as
My ability to hold in my memory things that I have learned
is.... Respondents were asked to compare their present memory with
their memory before they became ill (patients) or with their memory 1 year ago
(controls), on a nine-point scale from -4 (worse than before) to +4 (better
than before).
Other neurocognitive functions
![]() |
Clinical Implications and Limitations |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
LIMITATIONS
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSMIV).Washington, DC: APA.
Beck, A. T., Ward, C. H., Mendelson, M., et al (1961) An inventory for measuring depression. Archives of General Psychiatry, 4, 561 571.[Medline]
Berman, R. M., Narasímhan, M., Sanacora Sanacora, G., et al (2000) A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Biological Psychiatry, 57, 332 337.[CrossRef]
Bulla-Hellwig, M. & Spanhofer, D. (1996) Der Gedächtnis chtnis für Personen Test. Theoretischer Hintergrund und Materialentwicklung zweier Parallelformen zur alltagsnahen Gedächtnisprüfung. Zeitschrift für Neuropsychologie, 7, 16 24.
Collegium Internationale Psychiatriae Scalarum (eds) (1978) Internationale Skalen für Psychiatrie. Weinheim: Beltz Test Gesellschaft.
Cronholm, B. & Ottosson, J.-O. (1961) Memory functions in endogenous depression: before and after electroconvulsive therapy. Archives of General Psychiatry, 5, 193 199.[Medline]
Folkerts, H. (1997) Elektrokrampftherapie. Ein praktischer Leitfaden für die Klinik.Stuttgart:Enke.
Folstein, M.F., Folstein, S.E. & McHugh, P.R. (1975) Mini-Mental State. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189 198.[CrossRef][Medline]
Freeman, C. P., Weeks, D. & Kendell, R. E. (1980) ECT. II: Patients who complain. British Journal of Psychiatry, 137, 17 25.[Abstract]
Gold, J. M., Carpenter, C., Randolph, C., et al (1997) Auditory working memory and Wisconsin card sorting test performance in schizophrenia. Archives of General Psychiatry, 54, 159 165.[Abstract]
Grunhaus, L., Dannon, P. N., Schreiber, S., et al (2000) Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study. Biological Psychiatry, 47, 314 324.[CrossRef][Medline]
Grunhaus, L., Schreiber, S., Dolberg, O. T., et al (2003) A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression. Biological Psychiatry, 53, 324 331.[CrossRef][Medline]
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Clinical Psychiatry, 6, 278 296.
Hasse-Sander, I., Müller, H., Schurig, W., et al (1998) Auswirkungen der Elektrokrampftherapie auf die kognitiven Funktionen bei therapieresistenten Depressionen. Nervenarzt, 69, 609 616.[CrossRef][Medline]
Hautzinger, M., Bailer, M., Worall, H., et al (1994) Beck-Depressions-Inventar. Testhandbuch.Bern: Huber.
Helmstaedter, C., Lendt, M. & Lux, S. (2001) Verbaler Lernund Merkfähigkeitstest. Manual. Göttingen: Beltz.
Horn, W. (1983) Leistungs-Prüf-System (2nd edn). Göttingen: Hogrefe.
Janicak, P. G., Dowd, S. M., Martis, B., et al (2002) Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial. Biological Psychiatry, 51, 659 667.[CrossRef][Medline]
Kessler, J., Markowitsch, H. J. & Denzler, P. (1990) Mini-Mental-Status Test.Weinheim: Beltz.
Kopelman, M. D., Wilson, B. A. & Baddeley, A. D. (1990) The Autobiographical Memory Interview.Bury St Edmunds: Thames Valley Test.
Kosel, M., Frick, C., Lisanby, S. H., et al (2003) Magnetic seizure therapy improves mood in refractory major depression. Neuropsychopharmacology, 11, 2045 2048.
Lisanby, S.H., Maddox, J.H., Prudic, J., et al
(2000) The effects of electroconvulsive therapy on memory of
autobiographical and public events. Archives of General
Psychiatry, 57, 581
590.
Martin, J. L. R., Barbanoj, M. J., Schlaepfer, T. E., et
al (2003) Repetitive transcranial magnetic stimulation
for the treatment of depression: systematic review and meta-analysis.
British Journal of Psychiatry,
182, 480
491.
McCall, W.V. (2001) Electroconvulsive therapy in the era of modern psychopharmacology. International Journal of Neuropsychopharmacology, 4, 315 324.[CrossRef][Medline]
Prudic, J., Peyser, S. & Sackeim, H. A. (2000) Subjective memory complaints: a review of patient self-assessment of memory after electroconvulsive therapy. Journal of ECT, 16, 121 132.[Medline]
Reitan, R. M. (1979) Trail Making Test.Weinheim: Beltz.
Rey, A. (1964) LExamen de Clinique en Psychologie.Paris: Presses Universitaires.
Rose, D., Wykes, T., Leese, M., et al
(2003) Patients perspectives on electroconvulsive
therapy: systematic review. BMJ,
326, 1363
1367.
Sackeim, H. A., Prudic, J., Devanand, D. P., et al
(2000) A prospective, randomized, double-blind comparison of
bilateral and right unilateral electroconvulsive therapy at different stimulus
intensities. Archives of General Psychiatry,
57, 425
434.
Schlaepfer, T. E., Kosel, M. & Nemeroff, C. B. (2003) Efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of affective disorders. Neuropsychopharmacology, 28, 201 205.[CrossRef][Medline]
Schmidt, K.-H. & Metzler, P. (1992) Wortschatztest Handbuch.Weinheim: Beltz.
Squire, L.R. & Slater, P.C. (1983) Electroconvulsive therapy and complaints of memory dysfunction: a prospective three-year follow-up study. British Journal of Psychiatry, 142, 1 8.[Abstract]
Squire, L.R., Wetzel, C.D., Slater, P.C. (1979) Memory complaint after electroconvulsive therapy: assessment with a new self-rating instrument. Biological Psychiatry, 14, 791 801.[Medline]
Squire, L.R., Slater, P.C. & Miller, P.L. (1981) Retrograde amnesia and bilateral electroconvulsive therapy. Long-term follow-up. Archives of General Psychiatry, 38, 89 95.[Abstract]
Triggs, W. J., McCoy, K. J. M., Greer, R., et al (1999) (1999) Effects of left frontal transcranial magnetic stimulation on depressed mood, cognition and corticomotor threshold. Biological Psychiatry, 45, 1440 1446.[CrossRef][Medline]
UK ECT Review Group (2003) Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet, 361, 799 808.[CrossRef][Medline]
Wechsler, D. (1981) Wechsler Adult Intelligence Scale Revised. New York: Psychological Corporation.
Weeks, D., Freeman, C. P. & Kendell, R. E. (1980) ECT. III: Enduring cognitive deficits? British Journal of Psychiatry, 137, 26 37.[Abstract]
Weiner, R. D., Rogers, H. J., Davidson, J. R. T., et al (1986) Effects of stimulus parameters on cognitive side effects. Annals of the New York Academy of Science, 462, 315 325.[Medline]
Wilson, B., Cockburn, J. & Baddeley, A. (1991) The Rivermead Behavioural Memory Test.Suffolk:Thames. Suffolk: Thames Valley Test.
Received for publication April 13, 2004. Revision received September 23, 2004. Accepted for publication September 23, 2004.