Iberoamerican Cochrane Centre, Hospital de la Santa Crue i Sant Pau, Barcelona, Spain
Department of Pharmacology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
University Hospital Bern, Switzerland and The Johns Hopkins University, Baltimore, Maryland, USA
Iberoamerican Cochrane Centre, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Correspondence: José Luis Rodríguez Martin, Centro Cochrane Iberoamericano, Servei d'Epidemiologia Clínica i Salut Pública, Hospital de la Santa Creu i Sant Pau, Universidad Autónoma de Barcelona UAB, Casa de Convalescència, C/171 Sant Antoni Ma Claret, Barcelona 08041, Spain. E-mail: jrodriguezma{at}hsp.santpau.es
Declaration of interest The study was funded by the Ministerio de Sanidad y Consumo,Instituto de Salud Carlos III, Spain (grant no. 00/10099). T.E.S. is involved in one of the studies included in this review and is also SecretaryTreasurer of the International Society for Transcranial Stimulation.
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ABSTRACT |
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Aims To assess the efficacy of rTMS in treating depression.
Method We conducted a systematic review of randomised controlled trials that compared rTMS with sham in patients with depression. We assessed the quality of design of all studies and conducted a meta-analysis of data from trials with similar rTMS delivery.
Results We included a total of 14 trials. The quality of the included studies was low. Pooled analysis using the Hamilton Rating Scale for Depression showed an effect in favour of rTMS compared with sham after 2 weeks of treatment (standardised mean difference=0.35; 95% CI 0.66 to 0.04), but this was not significant at the 2-week follow-up (standardised mean difference=-0.33; 95% CI 0.84 to 0.17).
Conclusions Current trials are of low quality and provide insufficient evidence to support the use of rTMS in the treatment of depression.
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INTRODUCTION |
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METHOD |
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Inclusion criteria
Studies included were randomised trials that compared rTMS given at any
frequency and at any localisation with a sham intervention in patients of any
age and gender with a diagnosis of depression (depressive disorders or bipolar
disorders in depressed phase), with or without psychotic symptoms according to
either DSMIV (American Psychiatric
Association, 1994) or ICD10
(World Health Organization,
1993).
Selection procedure, data extraction and quality assessment
Potentially relevant studies were obtained, examined independently and
quantitative and qualitative data were extracted independently using a
standard form.
Our quality assessment of the studies addressed three main criteria: adequate concealment of randomisation; intention-to-treat analysis; and blinding. To assess the adequacy of randomisation concealment, we looked for evidence from the study report of robust concealment of group allocation, such as a centralised system or a process in which allocations were pre-numbered, coded and kept in locked files or in sequentially numbered, sealed, opaque envelopes (Clarke & Oxman, 2001). For intention-to-treat analysis we looked for evidence that all patients initially randomised had been included in the analysis, regardless of whether they had completed the study or not. We also looked for post-treatment follow-up. With respect to blinding, for practical reasons the professional giving the rTMS intervention itself (whether active rTMS or sham), cannot be blinded. If the patients had been blinded to the treatment allocation, and the outcomes had been assessed either by an assessor who was also blinded to the allocation or by the patient themselves, we classified the trial as being single blind with evaluation by external assessors.
We also looked at details of each trial design and noted whether there had been factors such as concurrent medication or therapeutic setting that may have influenced health outcomes and consequently the apparent performance of the interventions.
Outcome measures
The main outcome measure was remission of symptoms, determined by any of
the following measures: time to adjunctive treatment; readmission to hospital
or hospital discharge; time off work; or appropriate psychometric scales.
Acceptability of treatment (as measured by withdrawals from trial) was
considered as a secondary outcome.
Data synthesis
We undertook a methodological quality assessment of all the included
studies. We conducted a pooled analysis of data from those trials in which the
intervention given was homogeneous (same localisation, frequency and duration
of treatment), using scores from the Hamilton Rating Scale for Depression
(HRSD; Hamilton, 1960,
1967), because this
psychometric scale was the only outcome measure that was reported by all the
studies. In addition we conducted a second pooled analysis of data from those
studies with homogeneous interventions that had used the Beck Depression
Inventory (BDI; Beck et al,
1961) as a secondary outcome measure. A third pooled analysis was
conducted for treatment and acceptability (measured by withdrawals).
In the cross-over studies we excluded a possible carry-over effect between
the different phases of the trials by using information only from the first
phase (Jadad, 1998). For
continuous data the studies included in the pooled analysis were tested for
statistical homogeneity using a 2 test and, because
homogeneity was found, the pooled standardised mean difference was calculated
under a fixed-effect model weighted by the inverse variance method
(Cochrane Collaboration, 2000;
Sutton et al, 2000).
For binary outcomes the relative risks were calculated using a
MantelHaenszel fixed-effect model
(Cochrane Collaboration, 2000; Sutton et al, 2000)
and 95% confidence intervals were calculated. Standardised mean difference
(Geddes et al, 2002)
rather than weighted mean difference was used in the pooled analysis to take
account of the different versions of HRSD and BDI used in the different
studies.
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RESULTS |
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We excluded four RCTs and one control clinical trial (CCT) from the identified trials because there was either no sham comparison group (Conca et al, 1996; Grunhaus et al, 2000; Pridmore, 2000; Pridmore et al, 2000) or because, although a sham group was included alongside two randomly allocated active treatment groups the sham group itself had not been generated by a randomisation process (Kolbinger et al, 1995). A detailed analysis of these five studies was included as part of a wider systematic review (Martin et al, 2002).
Among the remaining sixteen randomised controlled studies there was clinical heterogeneity with respect to four variables: localisation of rTMS application (left dorsolateral prefrontal cortex, right prefrontal cortex, vertex or multiple sites; frequency of rTMS (high or low); duration of treatment10 consecutive working days (2 weeks) or 5 consecutive working days (1 week); and number of interventions a day (one or more) (see Fig. 1). Two studies (Pascual-Leone et al, 1996b; Speer et al, 2001) are awaiting evaluation of design data and methodological quality to be included, and additional quantitative information is needed for these studies to be analysed.
A total of thirteen published (George et al, 1997, 2000; Avery et al, 1999; Kimbrell et al, 1999; Klein et al, 1999; Loo et al, 1999; Padberg et al, 1999; Berman et al, 2000; Eschweiler et al, 2000; García-Toro et al, 2001a,b; Manes et al, 2001; Szuba et al, 2001) and one study in preparation (further details available from the authors upon request) met the inclusion criteria for assessing the effectiveness of rTMS v. a sham intervention (see Appendix 2). The majority of these studies (13/14) compared left-sided, high-frequency rTMS (lefthigh) with a group receiving sham, whereas one study (Klein et al, 1999) compared right-sided, low-frequency rTMS for 2 weeks (rightlow2). Treatment duration was for 2 weeks in nine of the lefthigh studies (lefthigh2) and for 1 week (lefthigh1) in the remaining three studies. Among the 12 lefthigh studies, all used the HRSD as a primary indicator of efficacy, whereas nine (seven with available data) also used the BDI as a secondary outcome. A quantitative analysis of pooled data from the lefthigh1 and lefthigh2 studies on each of these outcome scales was possible. Two studies (Kimbrell et al, 1999; Padberg et al, 2002) included a third left-sided, low-frequency (leftlow) comparison arm. Because of differences in the nature of the intervention applied with respect to localisation and frequency, these two comparisons (leftlow1 and leftlow2) were not included in the quantitative analysis, but were included in the qualitative review along with the one rightlow2 study and with one study that compared different doses of rTMS per day (Szuba et al, 2000).
Study populations
The mean age of study participants ranged from 41.8 to 60.87 years and the
ratio of males to females ranged from 0.09 to 2.33
(Table 1). Thirteen of fourteen
studies included in the qualitative review recruited patients who only
fulfilled the criteria for major depression or major depressive illness as
classified by DSMIV criteria. Only one study recruited patients with
criteria that included minor depression
(Manes et al, 2001). Some studies recruited only patients with unipolar depression whereas others
also recruited patients with bipolar depression in the depressed phase. Almost
all studies specified that patients who were at a high risk of suicide and/or
possible risk of convulsions were excluded.
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Quality of included studies
Most of the studies were of low methodological quality. Apart from one
study with 70 patients (Klein et
al, 1999), the rest used sample sizes of 640 patients
(median=19).
Randomisation
Most studies gave only general descriptions of the randomisation process
and none described the methods of concealing allocation. One study
(Klein et al, 1999)
described only the generation of the allocation sequence through randomised
lists of numbers generated by a computer program and another (further details
available from the authors upon request) reported a generation of
randomised numbers without giving details of the allocation process
involved.
Intention-to-treat
Although there were withdrawals from six of the included thirteen studies,
only two studies (Berman et al,
2000; Eschweiler et
al, 2000) undertook an intention-to-treat analysis by
including the last observation carried forward in the analysis. Three studies
(Avery et al, 1999;
García-Toro et al,
2001a,b)
included a period of post-treatment follow-up of 2 weeks, one study included a
period of post-treatment follow-up of 1 week
(Manes et al, 2001)
and another study (Eschweiler et
al, 2000) included a period of post-treatment follow-up of 1
week between the first and second phase of the cross-over design. One study
used the post-treatment follow-up for only one patient who responded totally
and for three who responded partially, but it did not report on the rest of
the patients treated in the study (Berman
et al, 2000).
Blinding
Although most of the studies stated that they were double blind or double
masked, they were, more accurately, single blind with evaluation by external
assessors. Nine (seven with available data) studies also used the BDI, in
which the patients themselves evaluated their response to treatment.
Confounding factors
Only three (Berman et al,
2000; Manes et al,
2001; Szuba et al,
2001) of the further studies stated that the patients were all
free of psychotic medication for 1 week before the study and during the study
period itself. In seven of fourteen studies the patients were described as
medication resistant (failed at least one trial of pharmacological therapy
during the current depressive episode) but in some cases pharmacological
treatments were continued and in some cases not
(Table 2).
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Although most studies stated that they excluded patients at a high risk of suicide, some studies recruited only out-patients (George et al, 1997, 2000; Avery et al, 1999; Manes et al, 2001; further details available from the authors upon request), others recruited only in-patients (Klein et al, 1999; Loo et al, 1999), some both in-patients and out-patients (Berman et al, 2000; García-Toro et al, 2001b) and others did not specify (Kimbrell et al, 1999; Padberg et al, 1999; Eschweiler et al, 2000; García-Toro et al, 2001a; Szuba et al, 2001).
Quantitative analyses
Repetitive TMS (left dorsolateral prefrontal cortex and high
frequency) v. sham TMS
Hamilton Rating Scale for Depression. Twelve studies contributed
to this analysis, giving an overall sample of 217 patients (119 in the
treatment group and 98 in the placebo group). A subgroup analysis was
conducted by duration of treatment (1 or 2 weeks) and for those studies that
included follow-up data (at 1 or 2 weeks). After 2 weeks of treatment the
standardised mean difference (SMD) for rTMS (left dorsolateral prefrontal
cortex, high frequency) v. sham TMS was 0.35 (95% CI
0.66 to 0.04; P=0.03; n=9), showing a difference in favour of
rTMS. For those studies that reported data after 1 week of treatment or only
gave treatment for 1 week, the SMD for rTMS (left dorsolateral prefrontal
cortex, high frequency) v. sham rTMS was not significant, at
0.18 (95% CI 0.64 to 0.27; P=0.4; n=5). After 1 week of
post-treatment follow-up, the SMD was 0.08 (95% CI 0.64 to 0.81;
P=0.8; n=2). After 2 weeks of post-treatment follow-up, the SMD was not
statistically significant: 0.33 (95% CI 0.84 to 0.17; P=0.2;
n=3) (Fig. 2).
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Beck Depression Inventory. Seven studies contributed to this analysis, giving an overall sample size of 145 patients (81 in the treatment group and 64 in the placebo group). No difference between rTMS and sham TMS was shown for any of the time periods. After 1 week of treatment, the SMD for the rTMS over the left dorsolateral prefrontal cortex and high-frequency v. sham TMS was 0.18 (95% CI 0.47 to 0.82; P=0.6; n=3). The SMD after 2 weeks of treatment was 0.24 (95% CI 0.58 to 0.11; P=0.18; n=6). The SMD after 2 weeks of post-treatment follow-up was 0.06 (95% CI 0.56 to 0.43; P=0.8; n=3) (Fig. 3).
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The analyses were repeated using a random-effects model, but this did not alter the results.
Acceptability of treatment. Four studies (lefthigh2) reported withdrawals of patients during the intervention period, with a total sample size of 114 patients (63 in the treatment group and 51 in the placebo group). The relative risk, using a fixed-effect model for rTMS v. sham rTMS for all patients was 0.88 (95% CI 0.37 to 2.13; P=0.8), which is a statistically non-significant difference.
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DISCUSSION |
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Although the SMD between active treatment and sham groups was significant in favour of the active group when measured by the HRSD immediately after 2 weeks of treatment with left-sided, high-frequency rTMS, this difference was not corroborated by a significant difference in the BDI. Furthermore, analysis of the results of those studies that tested patients at 2 weeks after the intervention period showed that any differences between the two groups had disappeared. Equally, analysis of data from trials that provided results after 1 week of treatment showed no significant effect.
Methodological considerations
The included studies all had serious methodological weaknesses. Of
particular note was the small sample size (median=19), a factor that is known
to introduce bias because uncontrolled variables that may influence outcomes
may not be sufficiently evenly distributed between treatment and control
groups (Colton, 1974). In all
except three of the studies, all or a proportion of the patients (in both
treatment and control groups) enrolled in the trials were on some form of
psychotropic medication. Although, in some cases, the authors stated that
patients were medication resistant the definition of resistant
was unclear and the potential for concurrent medication to interfere with the
possible performance of the rTMS intervention cannot be discounted.
None of the included studies provided information in the published report on the method of allocation concealment used. One of the major sources of selection bias in randomised trials is failure to conceal adequately the group to which a particular patient has been assigned until after that patient's eligibility for the trial has been assessed (Clarke & Oxman, 2001). Indeed, lack of allocation concealment has been reported to cause more bias than other components of the allocation process (Schulz et al, 1995). For example, in certain RCTs the patients who are most likely to respond are included only in the active treatment arm (Berger & Exner, 1999).
The person who gives an intervention such as rTMS obviously cannot be blinded as to whether they are actually administering the active treatment or a sham intervention. It is therefore more accurate to consider the trials as having been single blind with an evaluation by external blinded assessors (Martin & Casado Collado, 2002). Although, as Day (2000) has observed, blinding of outcome assessment may be more important than blinding administration, there is nevertheless potential for patients to guess their group allocation through non-verbal (albeit unintentional) communication with the administrator of the intervention. A further threat to the efficacy of the blind arises from the nature of the sham intervention. As recent authors have commented (Wassermann & Lisanby, 2001), depending on the way in which the sham is delivered, the physical sensation experienced can differ when receiving sham and active treatment, effectively unblinding the patient.
Measurement of treatment outcomes in depression is difficult and most clinical studies have made use of scales or inventories, of which the most common is the HRSD, based on a semi-structured interview. Some authors (Hotopf et al, 1999) have reported that rating scales based on semi-structured interviews are more susceptible to observation bias than are self-applied questionnaires such as the BDI. The lack of consistency in effect as determined by the two scalesa positive result after 2 weeks of treatment as measured by the HRSD and a negative result for the BDImakes definitive conclusions about the nature of the change in mood of the patients impossible. Because of difficulties with interpreting results from psychometric scales (Rosenberg, 2000) and the subjective or unstable character of this psychopathology, the use of other more objective outcome measures such as readmissions to hospital, time to hospital discharge, time to adjunctive treatment and time off work should be taken into account in the assessment of rTMS in the treatment of depression.
The complexity of the possible combinations for administering rTMS makes
the comparison of like with like particularly difficult. For our meta-analysis
we categorised the three main variations in administration method:
localisation of the intervention on the skull; frequency given; and the
duration of the treatment period. In the majority of included studies, rTMS
was applied to the left dorsolateral frontal cortex, but it has been pointed
out recently that the method for precisely targeting the stimulation in this
area is inherently unreliable (Wassermann
& Lisanby, 2001). Evidence that this is the optimal
localisation is also lacking. With respect to the frequency given, we
classified into high (>1 Hz) and low (1 Hz) frequency, according to
customary practice. Although localisation, frequency and treatment duration
were the main variations, other potential differences in the administration of
rTMS that we did not categorise include shape of the coil, number of trains
per session and the duration of each train.
Data analysis considerations
In eight of the twelve studies included in the meta-analysis for the HRSD
and in six of the seven included in the meta-analysis for the BDI, the
baseline mean values for the severity of depression were higher in the
treatment group than in the placebo group. Although these differences were not
statistically significant at the level of each individual study, they would
have introduced a potential bias within the meta-analysis of pooled data by
accentuating the tendency for regression to the mean of the more extreme
values (Davis, 1976). Our
study was limited because individual patient data were not available from all
the studies and an appropriate adjustment according to baseline severity was
not possible. In order to reduce, as much as possible, any potential bias
caused by these differences in baseline values, we compared final values on
depression severity between active and sham groups.
Before our study, a meta-analysis (McNamara et al, 2001) that included five studies found demonstrable beneficial effects of rTMS in depression. Our findings differ from this earlier paper with respect to the main unit of analysis: this earlier study used the difference in an undefined rate of improvement between groups from psychometric scales used in the trials. In our meta-analysis we used the means and standard deviations because we considered that, owing to probable baseline imbalance between the studies, these estimates reflect a more precise effect size than a dichotomous measure such as the rate of improvement apparently derived from the continuous data of the rating scales.
Consequences of the weak findings about rTMS
Repetitive TMS is a relatively affordable method of applying magnetic
fields non-invasively to the human brain. If safety precautions are followed,
it also appears to be safe, at least when given within the parameters studied
so far: between 1 and 4 weeks of treatment. The non-invasive nature of the
intervention has been among the factors that have led to the impetus to
research possible therapeutic effects in the treatment of depression and
especially in refractory depression, because few other (and certainly no
non-invasive) treatment options are currently available. The results of our
systematic review show that results to date are not very encouraging.
But this should not be a reason to abandon rTMS in affective disorders altogether. Many of the clinical treatments now used successfully in psychiatry have developed slowly, going through a process of initial enthusiastic approval followed by almost total demise and then back to sensible, widespread clinical use. Electroconvulsive therapyanother method of brain stimulation in affective disordersunderwent this very process. Evidence shows that rTMS has effects on the brain and it therefore has great potential as a research tool (Hallett, 2000; Lisanby et al, 2000). Data from animal studies demonstrate effects on expression of immediate early genes (Ji et al, 1998) and on neuroendocrinology (Keck et al, 2000), and rTMS either alone or combined with procedures such as functional neuroimaging (Speer et al, 2000,Speer et al, 2000) may be useful for testing functional connectivity, neuroplasticity and information processing. Repetitive TMS therefore can be used to test either general hypotheses concerning brain function at different levels or hypotheses concerning the underlying pathology of affective and other neuropsychiatric disorders. It is worthy of note that one of the only two studies included in the meta-analysis in which all the patients were free of medication before and during the rTMS trial was also the only individual study that showed a statistically significant positive effect on the HRSD for the intervention group.
Today, the total number of patients included in studies of the efficacy of rTMS in the treatment of depression falls far short of the numbers registered in trials for new drug treatments. In addition, many technical details, such as where to stimulate, at what frequency, the total number of stimuli and the duration of the treatment, have yet to be resolved. There is an urgent need for thorough, randomised, controlled, multi-centre studies involving large numbers of patients. Another problem is the lack of consensus about the possible explanatory mechanisms for any anti-depressant effects of TMS, but this is also the case for many other treatments in psychiatry. Repetitive TMS research is basically empirical: many variables play a role and a large number of parameters has to be explored carefully to find the most efficacious treatment.
Repetitive TMS clearly has effects on the brain, an observation that is remarkable in itself and it may well be that it is a treatment modality in search of a suitable application in psychiatry. It is of utmost importance, therefore, that the long and difficult path of research for potential clinical applications of rTMS in affective disorders should continue.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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APPENDIX 1: Studies included in the review |
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Berman, R. M., Narasimhan, M., Sanacora, G., et al (2000) A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Biological Psychiatry, 47, 332337.[CrossRef][Medline]
Eschweiler, W. G., Wegerer, C., Schlotter, W., et al (2000) Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression. Psychiatry ResearchNeuroimaging, 99, 161172.
García-Toro, M., Mayol, A., Amillas, H., et al (2001a) Modest adjunctive benefit with transcranial magnetic stimulation in medication-resistant depression. Journal of Affective Disorders, 64, 271275.[CrossRef][Medline]
García-Toro, M., Pascual-Leone, A., Romera, M., et al (2001b) Prefrontal repetitive transcranial magnetic stimulation as add on treatment in depression. Journal of Neurology and Psychiatry, 71, 546548.[CrossRef]
George, M. S., Wassermann, E. M., Kimbrell,T. A., et al
(1997) Mood improvement following daily left prefrontal
repetitive transcranial magnetic stimulation in patients with depression: a
placebo-controlled crossover trial. American Journal of
Psychiatry, 154,
17521756.
George, M.S., Nahas, Z., Molloy, M., et al (2000) A controlled trial of daily left prefrontal cortex TMS for treating trial of dailyleftprefrontalcortexTMS for depression. Biological Psychiatry, 48, 962970.[CrossRef][Medline]
Kimbrell, T. A., Little, J. T., Dunn, R. T., et al (1999) Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism. Biological Psychiatry, 46, 16031613.[CrossRef][Medline]
Klein, E., Kreinin, I., Chistyakov, A., et al
(1999) Therapeutic efficacy of right prefrontal slow
repetitive transcranial magnetic stimulation in major depression.
Archives of General Psychiatry,
56,
315320.
Loo, C., Mitchell, P., Sachdev, P., et al
(1999) Double-blind controlled investigation of transcranial
magnetic stimulation for the treatment of resistant major depression.
American Journal of Psychiatry,
156,
946948.
Manes, F., Jorge, R., Morcuende, M., et al (2001) A controlled study of repetitive transcranial magnetic stimulation as a treatment of depression in the elderly. International Psychogeriatrics, 13, 225231.[Medline]
Padberg, F., Zwanger, P., Thomas, H., et al (1999) Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS. Psychiatry Research, 88, 163171.[CrossRef][Medline]
Szuba, M.P., O'Reardon, J.P., Rai, A. S., Szuba, M. P., O'Reardon, J. P., Rai, A. et al (2001) Acute mood and thyroid stimulating hormone effects of transcranial magnetic stimulation in major depression. Biological Psychiatry, 50, 2227.[CrossRef][Medline]
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APPENDIX 2: Studies excluded in the review: AveryGeorgeHotzheimer Database of rTMS Depression Studies. http://www.ists.unibe.ch/ists/TMSAvery.htm. |
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Clark, L., McTavish, S. F. B., Harmer, C. J., et al (2000) Repetitive transcranial magnetic stimulation to right prefrontal cortex does not modulate the psychostimulant effects of amphetamine rTMS and amphetamine response. International Journal of Neuropsychopharmacology, 3, 297302.[CrossRef][Medline]
Conca, A., Koppi, S., König, P., et al (1996) Transcranial magnetic stimulation: A novel antidepressive strategy? Neuropsychobiology, 34, 204207.[Medline]
Conca, A., Swoboda, E., König, P., et al (2000) Clinical impacts of single transcranial magnetic stimulation (sTMS) as an add-on therapy in severely depressed patients under SSRI treatment. Human PsychopharmacologyClinical and Experimental, 15, 429438.[CrossRef]
D'Alfonso, A. A. L., Van Honk, J., Hermans, E., et al (2000) Laterality effects in selective attention to threat after repetitive transcranial magnetic stimulation at the prefrontal cortex in female subjects. Neuroscience Letters, 280, 195198.[CrossRef][Medline]
Eichhammer, P., Kharraz, A., Wiegand, R., et al (2002) Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation. Life Sciences, 70, 17411749.[CrossRef][Medline]
Epstein, C. M., Figiel, G. S., Mcdonald, W. M., et al (1998) Rapid rate transcranial magnetic stimulation in young and middle-aged refractory depressed patients. Psychiatric Annals, 28, 3639.
Feinsod, M., Kreinin, B., Chistyakov, A., et al (1998) Preliminary evidence for a beneficial effect of low-frequency, repetitive transcranial magnetic stimulation in patients with major depression and schizophrenia. Focus on Depression and Anxiety, 7, 6568.[CrossRef]
Figiel, G. S., Epstein, C., Mcdonald, W. M., et al (1998) The use of rapid-rate transcranial magnetic stimulation (rTMS) in refractory depressed patients. Neuroscience, 10, 2025.
García, M., Micó, J., Crespí, M., et al (1998) Estimulación magnética transcraneal repetitiva: una nueva intervención neurobiológica buscando un lugar en psiquiatría. A propósito de cinco casos. Psqiuiatría.COM, http://www.psiquiatria.com/psiquiatria/vol2num2/art_9.htm
Geller, V., Grisaru, N., Abarbanel, J. M., et al (1997) Slow magnetic stimulation of prefrontal cortex in depression and schizophrenia. Progress in Neuropsychopharmacology and Biological Psychiatry, 21, 105110.[CrossRef][Medline]
George, M. S., Wassermann, E. M., Williams, W. A., et al (1995) Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport, 6, 18531856.[Medline]
George, M. S., Wassermann, E. M., Williams, W. A., et al (1996) Changesin mood and hormone levels after rapid-rate transcranial magnetic stimulation (rTMS) of the prefrontal cortex. Journal of Neuropsychiatry and Clinical Neurosciences, 8, 172180.[Abstract]
George, M. S., Speer, A. M., Molloy, M., et al (1998) Low frequency daily left prefrontal rTMS improves mood in bipolar depression: a placebo-controlled case report. Human Psychopharmacology, 13, 271275.[CrossRef]
George, M. S., Lisanby, S. H. & Sackeim, H. A.
(1999a) Transcranial magnetic stimulation:
applications in neuropsychiatry. Archives of General
Psychiatry, 56,
300311.
George, M. S., Nahas, Z., Kozel, F. A., et al (1999b) Improvement of depression following transcranial magnetic stimulation. Current Psychiatry Reports, 1, 114124.[Medline]
Grisaru, N., Chudakov, B.,Yaroslavsky,Y., et al
(1998) Transcranial magnetic stimulation in mania: a
controlled study. American Journal of Psychiatry,
155,
16081610.
Grunhaus, L., Dannom, P. N., Schreiber, S., et al (2000) Repetitive transcranial magnetic stimulation is an effective electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study. Biological Psychiatry, 47, 314324.[CrossRef][Medline]
Habel, U., Wild, B., Topka, H., et al (2001) Transcranial magnetic stimulation: no effect on mood with single pulse during learned helplessness. Progress in Neuropsychopharmacology and Biological Psychiatry, 25, 497506.[CrossRef][Medline]
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Received for publication August 2, 2002. Revision received November 11, 2002. Accepted for publication December 3, 2002.
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