Transcrtanial Magnetic Stimulation for Depression:
Recent Publications.
Recent Publications.
Psychiatry Res. 2006 Nov 22;148(1):33-45. Epub 2006 Oct 5.
An analysis of functional neuroimaging studies of dorsolateral prefrontal
cortical activity in depression.
Fitzgerald PB, Oxley TJ, Laird AR, Kulkarni J, Egan GF, Daskalakis ZJ.
Alfred Psychiatry Research Centre, The Alfred and Monash University Department
of Psychological Medicine, Commercial Rd, Melbourne, Victoria 3004, Australia.
Repetitive transcranial magnetic stimulation (rTMS) is currently undergoing
active investigation for use in the treatment of major depression. Recent
research has indicated that current methods used to localize the site of
stimulation in dorsolateral prefrontal cortex (DLPFC) are significantly
inaccurate. However, little information is available on which to base a choice
of stimulation site. The aim of the current study was to systematically examine
imaging studies in depression to attempt to identify whether there is a pattern
of imaging results that suggests an optimal site of stimulation localization. We
analysed all imaging studies published prior to 2005 that examined patients with
major depression. Studies reporting activation in DLPFC were identified. The
DLPFC regions identified in these studies were analysed using the Talairach and
Rajkowska-Goldman-Rakic coordinate systems. In addition, we conducted a
quantitative meta-analysis of resting studies and studies of serotonin reuptake
inhibitor antidepressant treatment. There was considerable heterogeneity in the
results between studies. Changes in Brodmann area 9 were relatively consistently
identified in resting, cognitive activation and treatment studies included in
the meta-analysis. However, there was little consistency in the direction of
these changes or the hemisphere in which they were identified. At this stage,
the results of imaging studies published to date have limited capacity to inform
the choice of optimal prefrontal cortical region for the use in rTMS treatment
studies.
PMID: 17029760 [PubMed - in process]
Int J Neuropsychopharmacol. 2006 Sep 7;:1-12 [Epub ahead of print]
A randomized trial of low-frequency right-prefrontal-cortex transcranial
magnetic stimulation as augmentation in treatment-resistant major depression.
Fitzgerald PB, Huntsman S, Gunewardene R, Kulkarni J, Daskalakis ZJ.
Alfred Psychiatry Research Centre, The Alfred and Monash University Department
of Psychological Medicine, Melbourne, Victoria, AustraliaThe Victoria Clinic,
Prahran, Melbourne, Australia.
Low-frequency right prefrontal repetitive transcranial magnetic stimulation
(rTMS) appears to have antidepressant properties although the effectiveness of
this treatment in clinical practice has not been assessed nor have the optimal
stimulation parameters been adequately defined. A total of 130 patients with
treatment-resistant depression were randomized to either 1- or 2-Hz rTMS over
the right prefrontal cortex (PFC) for 2 wk with a possible further 2 wk
extension. Non- responders were randomized to either 5- or 10-Hz left PFC rTMS.
Overall, 66 patients (51%) achieved response and 35 (27%) remission criteria.
For right-sided treatment, depression significantly improved but there was no
between-group difference. Twenty-eight (42%) patients in the 1-Hz group and 33
(53%) patients in the 2-Hz group achieved response criteria (chi2=1.40, p>0.05).
Depression symptom scores also improved for patients who crossed over to
left-sided treatment but there was no significant difference in response between
5- and 10-Hz rTMS. Despite a heterogeneous sample, a significant proportion of
patients met clinical response criteria following treatment but response to 1
and 2 Hz did not differ. 2-Hz right PFC rTMS has antidepressant properties but
offers no advantage over 1 Hz despite doubling pulse number.
PMID: 16959055 [PubMed - as supplied by publisher]
Aust N Z J Psychiatry. 2006 Sep;40(9):764-8.
Naturalistic study of the use of transcranial magnetic stimulation in the
treatment of depressive relapse.
Fitzgerald PB, Benitez J, de Castella AR, Brown TL, Daskalakis ZJ, Kulkarni J.
Alfred Psychiatry Research Centre, Department of Psychological Medicine, Monash
University, Melbourne, Victoria, Australia. paul.fitzgerald@med.monash.edu.au
BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS)
in the treatment of depression has been assessed in a number of acute treatment
trials during the last 10 years. Little is known about the long-term impact of
the treatment on the disorder and its effectiveness when applied for repeated
relapses of depression over time. METHOD: Nineteen patients who had previously
responded to rTMS in clinical trials received treatment with rTMS for a total of
30 episodes of depressive relapse. RESULTS: Approximately 10 months elapsed
between treatment episodes. The majority of patients achieved a significant
improvement in each treatment course with significant improvements achieved in
patients treated with both low-frequency right-sided rTMS and high-frequency
left-sided rTMS. CONCLUSIONS: The study suggests that rTMS may have value in the
treatment of episodes of depressive relapse with little reduction in efficacy
over time.
PMID: 16911751 [PubMed - in process]
Aust N Z J Psychiatry. 2006 Sep;40(9):759-63.
Daily and spaced treatment with transcranial magnetic stimulation in major
depression: a pilot study.
Turnier-Shea Y, Bruno R, Pridmore S.
Department of Psychological Medicine, Royal Hobart Hospital, and School of
Psychology, University of Tasmania, Australia.
OBJECTIVE: Transcranial magnetic stimulation is an emerging treatment of
treatment-resistant depression. Current protocols rely on daily treatments. This
study was designed to determine whether the time period over which treatment is
delivered is an important factor in efficacy. METHOD: Sixteen adult patients
with treatment-resistant major depression were randomly assigned to one of the
two treatment groups, both of which received 2 weeks of treatment. One group
received daily treatment (10 treatments, on business days). The other group
received three treatments in week one, and two treatments in week two (five
treatments, on spaced business days). Mood was rated using the Hamilton
Depression Rating Scale (HDRS) and a self-rated visual analogue scale. Response
was defined as a 50% reduction in HDRS rating, and remission was defined as
achieving an HDRS score of 8 or less. The groups were compared throughout the
2-week study period. RESULTS: At entry, there were no demographic differences
between the groups. Multivariate tests showed a significant main effect for time
(Pillai trace=0.76, F(4,56)=8.56, p<0.001, power=0.99) reflecting the
improvement in both measures of depression during treatment. There was no
significant difference between the groups overall (Pillai trace=0.25,
F(2,13)=2.12, p=0.16, power=0.36). Additionally, there was no significant
interaction between time and treatment group (Pillai trace=0.18, F(4,56)=1.35,
p=0.26, power=0.39) indicating that the significant improvement in depression
over time was similar for both treatment groups. There were no significant
differences in response and remission rates between the groups. CONCLUSION: The
time period of treatment appeared to be an important outcome factor. This
suggests that less than daily transcranial magnetic stimulation treatment may be
a useful clinical alternative.
PMID: 16911750 [PubMed - in process]
Int J Neuropsychopharmacol. 2006 Aug 21;:1-10 [Epub ahead of print]
Comparison of repetitive transcranial magnetic stimulation and electroconvulsive
therapy in unipolar non-psychotic refractory depression: a randomized,
single-blind study.
Rosa MA, Gattaz WF, Pascual-Leone A, Fregni F, Rosa MO, Rumi DO, Myczkowski M,
Silva MF, Mansur C, Rigonatti SP, Jacobsen Teixeira M, Marcolin MA.
Institute of Psychiatry, University of Sao Paulo, Sao Paulo - SP, Brazil.
Repetitive transcranial magnetic stimulation (rTMS) can induce significant
antidepressant effects and, for some patients, might be an alternative to
electroconvulsive therapy (ECT). The results of studies comparing the efficacy
of rTMS and ECT are mixed and, therefore, comparison of these two therapies
needs to be further explored. Forty-two patients aged between 18 and 65 yr,
referred to ECT due to unipolar non-psychotic depression refractoriness entered
the trial. They were randomly assigned to receive either rTMS or ECT. Depressive
symptom changes were blindly measured by Hamilton Depression Rating Scale,
Visual Analogue Scale and Clinical Global Impression at baseline, after 2 wk and
after 4 wk of treatment. There was no difference in the antidepressant efficacy
of ECT and rTMS. Response rates were relatively low in both groups (40% and 50%
respectively), with no significant difference between them (p=0.55). Remission
rates were also low for both groups (20% and 10% respectively), also with no
significant difference (p=0.631). There was no significant difference in the
neuropsychological test performance after either one of these therapies. Both
treatments were associated with a degree of improvement in refractory depression
and therefore add to the literature that rTMS can be an effective option to ECT
as it is a less costly treatment and is not associated with anaesthetic and
other ECT risks.
PMID: 16923322 [PubMed - as supplied by publisher]
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jul;30(5):960-2. Epub 2006
Apr 24.
Repetitive transcranial magnetic stimulation (rTMS) in a patient suffering from
comorbid depression and panic disorder following a myocardial infarction.
Sakkas P, Psarros C, Papadimitriou GN, Theleritis CG, Soldatos CR.
Athens University Medical School, Psychiatry Department, Eginitio Hospital, 74
Vas. Sofias Avenue, Athens 11528, Greece. psakkas@cc.uoa.gr
Application of repetitive transcranial magnetic stimulation was effective and
safe in treating a 55-year-old man with comorbid depression and panic disorder,
which occurred 6 months after a myocardial infarction.
Publication Types:
Case Reports
PMID: 16631291 [PubMed - indexed for MEDLINE]
Biol Psychol. 2006 Jun;72(3):271-7. Epub 2005 Dec 15.
Depressed mood, index finger force and motor cortex stimulation: a transcranial
magnetic stimulation (TMS) study.
Oathes DJ, Ray WJ.
Department of Psychology, The Pennsylvania State University, University Park, PA
16802, USA. djo155@psu.edu
The present study utilized transcranial magnetic stimulation (TMS) of the motor
cortex to understand basic motor processes associated with depressive symptoms
independent of cognitive requirements or diagnostic category. To assess the
integrity of the basic cortical-spinal-motor circuit associated with depressed
mood, TMS to the motor cortex was used to initiate motor evoked potentials
(MEPs) in forearm EMG and force production measured in the right (dominant)
index finger. While at rest, a group with more depressive symptoms showed less
force response in the index finger following stimulations compared with a group
endorsing less depressive symptoms. A negative correlation between force
response in the index finger at baseline (rest) following stimulation and the
Beck depression inventory indicated that depressive mood symptom elevations were
associated with less response to stimulations. The results argue for a greater
importance placed on the relationship between depressive mood symptoms and basic
motor processes.
PMID: 16359768 [PubMed - indexed for MEDLINE]
Aust N Z J Psychiatry. 2006 May;40(5):406-13.
Comment in:
Aust N Z J Psychiatry. 2006 May;40(5):379-80.
Transcranial magnetic stimulation for depression.
Mitchell PB, Loo CK.
School of Psychiatry, University of New South Wales, Black Dog Institute, Prince
of Wales Hospital, Randwick, Australia. phil.mitchell@unsw.edu.au
OBJECTIVE: To review the accumulated literature on the efficacy, safety and
predictors of response for repetitive transcranial magnetic stimulation (rTMS)
in the treatment of depression. METHODS: A descriptive review of the more than
25 published sham-controlled rTMS studies in depression was undertaken, focusing
on reported meta-analyses as well as individual trial reports. Potential
determinants of efficacy were examined, including the form of shams employed,
stimulation parameters and clinical features. RESULTS: There is now clear
evidence for the statistical superiority of left-prefrontal high frequency rTMS
compared with sham therapy. However, the clinical benefits are marginal in the
majority of reports. There is also still considerable uncertainty concerning the
optimal stimulation parameters. Those clinical features which appear to be
associated with greater response include younger age, lack of refractoriness to
antidepressants and no psychotic features. CONCLUSIONS: Current studies confirm
statistical efficacy, but insubstantive clinical benefit. Large multicentre
studies currently underway should clarify if rTMS should be approved by
regulatory agencies for widespread clinical availability. Furthermore, there is
a need to clarify the preferred parameters for administering this treatment.
Publication Types:
Review
PMID: 16683966 [PubMed - indexed for MEDLINE]
J Psychopharmacol. 2006 May;20(3 Suppl):35-40.
Neurostimulation in resistant depression.
Carpenter LL.
Department of Psychiatry, Brown University, Providence, RI 02906, USA.
linda_carpenter_md@brown.edu
Drugs and psychotherapy are inadequate for relieving depressive symptoms in a
substantial portion of severely depressed patients. In that patient group,
neurostimulation techniques such as electroconvulsive therapy, transcranial
magnetic stimulation, magnetic seizure therapy, vagus nerve stimulation and deep
brain stimulation could be lifesaving therapies. Neurostimulation is a physical
intervention that utilizes application of either electric current or a magnetic
field to directly stimulate the brain or central nervous system. This article
presents an overview of currently available neurostimulatory techniques for
depression, including a review of their efficacy and safety. Further development
and evaluation of non-pharmacological antidepressant therapies are needed, with
the hope of improving treatment of refactory depression.
PMID: 16644770 [PubMed - in process]
J Psychiatr Res. 2006 Mar 20; [Epub ahead of print]
Positive predictors for antidepressive response to prefrontal repetitive
transcranial magnetic stimulation (rTMS).
Brakemeier EL, Luborzewski A, Danker-Hopfe H, Kathmann N, Bajbouj M.
Department of Psychiatry and Psychotherapy, Charite - Universitatsmedizin
Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany.
Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation
technique which had recently been investigated as a putative antidepressant
intervention. However, there is little agreement about clinically useful
predictors of rTMS outcome. Therefore, the objective of the present study was to
determine whether specific biographical, clinical, and psychopathological
parameters are associated with the antidepressant response to rTMS in a large
sample of 70 depressive patients. We performed a logistic regression analysis in
70 patients with major depressive disorder treated with rTMS of the left
dorsolateral prefrontal cortex testing the predictive value of various domains
of the depression syndrome as well as the variables episode duration, degree of
treatment resistance, and CORE criteria. Response was defined as a 50% reduction
of the initial Hamilton score (HAMD). After two weeks of treatment, 21% of the
patients showed a response to rTMS. The binary logistic regression model
correctly assigned 86.7% of the responders and 96.4% of the non-responders to
their final response group. In the model, a high level of sleep disturbances was
a significant predictor for treatment response to rTMS. Also, a low score of
treatment resistance and a short duration of episode were positive predictors.
These findings provide new evidence that especially pronounced sleep
disturbances may be a significant clinical predictor of a response to rTMS.
Prospective rTMS studies are necessary to validate the predictive value of the
derived model.
PMID: 16554071 [PubMed - as supplied by publisher]
Australas Psychiatry. 2006 Mar;14(1):81-5.
Transcranial magnetic stimulation in adolescent depression.
Loo C, McFarquhar T, Walter G.
School of Psychiatry, University of New South Wales, Australia.
colleen.loo@unsw.edu.au
OBJECTIVE: There are few safe and effective biological treatments for major
depression in adolescents. We aimed to report the use of repetitive transcranial
magnetic stimulation (rTMS) as a treatment for adolescents with this condition.
METHODS: The first two subjects in a double-blind, sham-controlled trial of rTMS
that is evaluating the efficacy and safety of rTMS in depressed adolescents are
described. Clinical response was assessed at baseline and at the end of each
week. The following scales were used: Montgomery-Asberg Depression Rating Scale,
Clinical Global Impression-Severity Scale, Beck Depression Inventory and Centre
for Epidemiological Studies - Depression - Child Scale. A battery of cognitive
tests was also used at several intervals to measure potential change in
neuropsychological functioning. RESULTS: Random allocation of both subjects was
to active treatment. Both subjects improved to a clinically significant degree
with rTMS treatment and reported no adverse effects. Neuropsychological testing
did not demonstrate any deterioration in the domains of functioning tested.
CONCLUSIONS: Repetitive transcranial magnetic stimulation shows early promise as
a treatment for major depression in adolescents. Well-designed, sham-controlled
studies are now indicated to test the efficacy and safety of rTMS in these
patients.
Publication Types:
Case Reports
Randomized Controlled Trial
PMID: 16630205 [PubMed - indexed for MEDLINE]
Pharmacopsychiatry. 2006 Mar;39(2):52-9.
High-frequency repetitive transcranial magnetic stimulation improves refractory
depression by influencing catecholamine and brain-derived neurotrophic factors.
Yukimasa T, Yoshimura R, Tamagawa A, Uozumi T, Shinkai K, Ueda N, Tsuji S,
Nakamura J.
Department of Psychiatry, University of Occupational and Environmental Health,
1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a
non-invasive and easily tolerated method of altering cortical physiology. To
date, numerous open and sham controlled clinical trials have explored the
antidepressant potential of rTMS. In the present study, we investigated clinical
trials of high-frequency rTMS (20 Hz) for treatment of refractory depression,
and also examined the effect of rTMS on plasma levels of catecholamine
metabolites and brain-derived neurotropic factor (BDNF). METHODS: Twenty-six
depressed inpatients who met the DSM-IV criteria for major depressive disorder
and had failed to respond to treatment with at least two antidepressant drugs
given at adequate doses (above 150 mg/day in an equivalent dose of imipramine)
and durations (at least 4 weeks for each drug) were enrolled in this study.
Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78
years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left
prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily
sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and
homovanillic acid (HVA) were analyzed by high-performance liquid chromatography.
The plasma levels of BDNF were also measured with the sandwich ELISA method.
RESULTS: The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of
20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS.
Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by
rTMS. The levels of plasma MHPG, but not those of HVA, were significantly
reduced after rTMS treatment, and a negative correlation was observed between
the change in plasma MHPG levels and the change in scores of agitation. In
addition, the plasma levels of BDNF were significantly increased by 23 % in
responders and partial responders, but not in nonresponders, after rTMS
treatment, and a trend for association was found between the changes in Ham-D
scores and changes in plasma BDNF levels in all patients after rTMS treatment.
CONCLUSION: These results suggest that rTMS treatment brings about some
improvement in refractory depression, especially for symptoms such as agitation,
by influencing MHPG and BDNF, which is in accordance with previous reports
showing that BDNF was increased by various antidepressants treatments.
PMID: 16555165 [PubMed - indexed for MEDLINE]
Psychiatry Res. 2006 Jan 30;141(1):1-13. Epub 2005 Dec 13.
Effect of low-frequency transcranial magnetic stimulation on an affective
go/no-go task in patients with major depression: role of stimulation site and
depression severity.
Bermpohl F, Fregni F, Boggio PS, Thut G, Northoff G, Otachi PT, Rigonatti SP,
Marcolin MA, Pascual-Leone A.
Harvard Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA 02215, USA. felix.bermpohl@charite.de
Repetitive transcranial magnetic stimulation (rTMS) holds promise as a
therapeutic tool in major depression. However, a means to assess the effects of
a single rTMS session on mood to guide subsequent sessions would be desirable.
The present study examined the effects of a single rTMS session on an affective
go/no-go task known to measure emotional-cognitive deficits associated with
major depression. Ten patients with an acute episode of unipolar major
depression and eight partially or completely remitted (improved) patients
underwent 1 Hz rTMS over the left and right dorsolateral prefrontal cortex prior
to task performance. TMS over the mesial occipital cortex was used as a control.
We observed significantly improved performance in depressed patients following
right prefrontal rTMS. This beneficial effect declined with decreasing
depression severity and tended to reverse in the improved group. Left prefrontal
rTMS had no significant effect in the depressed group, but it resulted in
impaired task performance in the improved group. Our findings indicate that the
acute response of depressed patients to rTMS varies with the stimulation site
and depression severity. Further studies are needed to determine whether the
present paradigm could be used to predict antidepressant treatment success or to
individualize stimulation parameters according to specific pathology.
PMID: 16352348 [PubMed - indexed for MEDLINE]
Biol Psychiatry. 2006 Jan 15;59(2):187-94. Epub 2005 Sep 1.
A controlled study of repetitive transcranial magnetic stimulation in
medication-resistant major depression.
Avery DH, Holtzheimer PE 3rd, Fawaz W, Russo J, Neumaier J, Dunner DL, Haynor
DR, Claypoole KH, Wajdik C, Roy-Byrne P.
Department of Psychiatry and Behavioral Sciences, University of Washington
School of Medicine, Harborview Medical Center, Seattle, 98104-2499, USA.
averydh@u.washington.edu
BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) as a treatment
for depression has shown statistically significant effects, but the clinical
significance of these effects has been questioned. METHODS: Patients with
medication-resistant depression were randomized to receive 15 sessions of active
or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at
110% the estimated prefrontal cortex threshold. Each session consisted of 32
trains of 10 Hz repetitive TMS delivered in 5-second trains. The primary end
point was treatment response defined as a >or=50% decrease in Hamilton
Depression Rating Scale (HDRS) score at both 1 and 2 weeks following the final
repetitive TMS treatment. Remission was defined as a HDRS score < 8. RESULTS:
The response rate for the TMS group was 30.6% (11/35), significantly (p = .008)
greater than the 6.1% (2/33) rate in the sham group. The remission rate for the
TMS group was 20% (7/35), significantly (p = .033) greater than the 3% (1/33)
rate in the sham group. The HDRS scores showed a significantly (p < .002)
greater decrease over time in the TMS group compared with the sham group.
CONCLUSIONS: Transcranial magnetic stimulation can produce statistically and
clinically significant antidepressant effects in patients with
medication-resistant major depression.
Publication Types:
Randomized Controlled Trial
PMID: 16139808 [PubMed - indexed for MEDLINE]
Am J Psychiatry. 2006 Jan;163(1):88-94.
A randomized, controlled trial of sequential bilateral repetitive transcranial
magnetic stimulation for treatment-resistant depression.
Fitzgerald PB, Benitez J, de Castella A, Daskalakis ZJ, Brown TL, Kulkarni J.
Alfred Psychiatry Research Centre, the Alfred and Monash University Department
of Psychological Medicine, Melbourne, Victoria, Australia.
paul.fitzgerald@med.monash.edu.au
OBJECTIVE: High-frequency left-side repetitive transcranial magnetic stimulation
(rTMS) and low-frequency stimulation to the right prefrontal cortex have both
been shown to have antidepressant effects, but doubts remain about the magnitude
of previously demonstrated treatment effects. The authors evaluated sequentially
combined high-frequency left-side rTMS and low-frequency rTMS to the right
prefrontal cortex for treatment-resistant depression. METHOD: The authors
conducted a 6-week double-blind, randomized, sham-controlled trial in 50
patients with treatment-resistant depression. Three trains of low-frequency rTMS
to the right prefrontal cortex of 140 seconds' duration at 1 Hz were applied
daily, followed immediately by 15 trains of 5 seconds' duration of
high-frequency left-side rTMS at 10 Hz. Sham stimulation was applied with the
coil angled at 45 degrees from the scalp, resting on the side of one wing of the
coil. The primary outcome variable was the score on the Montgomery-Asberg
Depression Rating Scale. RESULTS: There was a significantly greater response to
active than sham stimulation at 2 weeks and across the full duration of the
study. A significant proportion of the study group receiving active treatment
met response (11 of 25 [44%]) or remission (nine of 25 [36%]) criteria by study
end compared to the sham stimulation group (two of 25 [8%] and none of 25
respectively). CONCLUSIONS: Sequentially applying both high-frequency left-side
rTMS and low-frequency rTMS to the right prefrontal cortex, has substantial
treatment efficacy in patients with treatment-resistant major depression. The
treatment response accumulates to a clinically meaningful level over 4 to 6
weeks of active treatment.
Publication Types:
Randomized Controlled Trial
PMID: 16390894 [PubMed - indexed for MEDLINE]
Expert Rev Neurother. 2006 Jan;6(1):73-80.
Current and emerging somatic treatment strategies in psychotic major depression.
Dannon PN, Lowengrub K, Gonopolski Y, Kotler M.
The Rehovot Community Mental & Rehabilitation Center, Tel Aviv University,
Rehovot, Israel. pinhasd@post.tau.ac.il
Psychotic major depressive disorder (MDD) is a mood disorder characterized by
severe affective and neurovegetative symptoms together with the presence of
delusions and/or hallucinations. It is a common disorder seen in a quarter of
consecutively admitted depressed patients and is often associated with severe
symptomatology, increased suicide risk, poor acute response to antidepressants
and poor acute and long-term treatment outcome. It is possible that poor
response in psychotic depression is caused by the fact that we have yet to
identify the most efficacious treatment protocol for psychotic MDD. Multiple
studies have shown that modifications in the treatment paradigm may increase
treatment efficacy in psychotic MDD. It has been generally accepted that, during
the acute treatment phase, antidepressant-antipsychotic drug combination therapy
is more effective than either treatment alone, although this strategy has
recently been challenged. The question of the optimal duration of
pharmacotherapy in order to prevent relapse and improve long-term (i.e., 5-year)
outcome is a focus of current investigation. This article will review currently
recommended treatment strategies for the acute, continuation and maintenance
phases of therapy. In particular, it will address the role of newer-generation
antidepressants, the role of second-generation antipsychotics, the use of mood
stabilizers and indications for electroconvulsive therapy. Other possible
treatment strategies such as transcranial magnetic stimulation, vagus nerve
stimulation, deep-brain stimulation and glucocorticoid receptor antagonists will
be discussed. Current recommendations for the prevention of relapse and
improvement of long-term outcome will be reviewed.
Publication Types:
Review
PMID: 16466314 [PubMed - indexed for MEDLINE]
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jan;30(1):126-30. Epub 2005
Oct 20.
A double-blind sham controlled study of right prefrontal repetitive transcranial
magnetic stimulation (rTMS): therapeutic and cognitive effect in medication free
unipolar depression during 4 weeks.
Januel D, Dumortier G, Verdon CM, Stamatiadis L, Saba G, Cabaret W, Benadhira R,
Rocamora JF, Braha S, Kalalou K, Vicaut PE, Fermanian J.
Unite de recherche clinique, EPS de Ville Evrard a Saint Denis, G03, 5 Rue du Dr
Delafontaine 93200 Saint-Denis, France. urcve@freesurf.fr
BACKGROUND: Transcranial magnetic stimulation (TMS) has become a therapeutic
tool in psychiatric diseases. METHODOLOGY: The objective was to evaluate the
efficacy of TMS in unipolar depression: the percentage of responders (>50% HDRS
reduction) and remission (HDRS score < or =8, after four weeks of active TMS
treatment in depressed patients free of any antidepressive agent versus
placebo-TMS. RESULTS: 27 patients were randomized in two groups: rTMS (N=11)
versus sham TMS (N=16). Statistical differences were detected between sham and
TMS treated groups on remission (0/16 versus 4/11 p=0.032, 1/16 versus 6/11
0.028 and 1/16 versus 7/11 p=0.011 at day 14, day 21 and day 28, respectively)
and on response (2/16 versus 5/11 at day 14 (NS), 2/16 versus 7/11 p=0.0115 at
day 21 and 1/16 versus 7/11 (p=0.025) day 28, respectively, using the exact
Fisher test). Significant differences were observed between day 1 versus day 8
(p<0.01), day 15, day 21 and day 28 (p<0.001) in TMS group and only versus day
21 (p<0.01) and day 28 (p<0.05) for the sham group. ANOVA comparison between TMS
and sham groups was significant at day 14 and day 28 (p<0.05). LIMITATIONS: The
few number of patients. CONCLUSION: Our study has shown an efficacy of right
rTMS in free medication unipolar depression over a month. Nevertheless, number
of patients included is limited and multicentric studies will be necessary to
specify the antidepressive action of TMS.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 16242826 [PubMed - indexed for MEDLINE]
World J Biol Psychiatry. 2006;7(4):261-4.
Induction of a mixed depressive episode during rTMS treatment in a patient with
refractory major depression.
Rachid F, Golaz J, Bondolfi G, Bertschy G.
Division of Adult Psychiatry, University Hospitals of Geneva, Switzerland.
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive
experimental technique which has mostly been investigated in the treatment of
mood disorders with possible efficacy in depression. Among its potential side
effects, there have been some reports of rTMS-induced (hypo)mania in the
literature but none for rTMS-induced mixed episodes. We report the case of a
39-year-old woman suffering from refractory chronic major depression who
developed a depressive mixed episode associated with a mild serotonin syndrome
during her second week of rTMS treatment. She was receiving a combination of
antidepressants, the doses of which were kept unchanged during rTMS treatment.
Mixed as well as manic episodes may be induced by transcranial magnetic
stimulation, complications already observed with antidepressants and
electroconvulsive therapy. Therefore, caution should be exercised among
clinicians using this experimental procedure, particularly in the treatment of
bipolar depressed patients.
PMID: 17071547 [PubMed - in process]
Cogn Behav Neurol. 2005 Dec;18(4):223-7.
The effects of repetitive transcranial magnetic stimulation (rTMS) on procedural
memory and dysphoric mood in patients with major depressive disorder.
O'Connor MG, Jerskey BA, Robertson EM, Brenninkmeyer C, Ozdemir E, Leone AP.
Harvard Medical School, Boston, MA, USA. moconnor@caregroup.harvard.edu
OBJECTIVE: To study the effects of depression and treatment with repetitive
transcranial magnetic stimulation (rTMS) on sequence learning. BACKGROUND:
Prefrontal dysfunction in depression may affect sequence learning and be
amenable to normalization by rTMS. METHOD: The serial reaction time test (SRTT)
was administered to 19 patients with major depressive disorder (MDD) and 20
nondepressed control participants. MDD patients were examined before and
following treatment with rTMS to the left dorsolateral prefrontal cortex in
daily sessions of 1600 stimuli at 10 Hz and at an intensity of 110% of the motor
threshold. Treatment occurred over a 2-week interval of time. RESULTS: MDD and
nondepressed groups differed significantly with respect to baseline response
speed. Following treatment with rTMS, MDD participants demonstrated
significantly improved mood, improved response speed, and improved procedural
learning. CONCLUSIONS: Findings suggest that rTMS over a 2-week period improves
performance on tasks of response speed and procedural memory in patients with
MDD. These cognitive effects are greater in those patients who showed a
significant antidepressant effect to rTMS intervention.
Publication Types:
Clinical Trial
PMID: 16340396 [PubMed - indexed for MEDLINE]
J Clin Psychiatry. 2005 Dec;66(12):1569-75.
Does rTMS hasten the response to escitalopram, sertraline, or venlafaxine in
patients with major depressive disorder? A double-blind, randomized,
sham-controlled trial.
Rossini D, Magri L, Lucca A, Giordani S, Smeraldi E, Zanardi R.
Department of Psychiatry, School of Medicine, Vita-Salute University, San
Raffaele Hospital, Via Stamina d'Ancona 20, 20127 Milan, Italy.
BACKGROUND/OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has
been mainly studied as adjunctive treatment for drug-resistant patients. We
assessed the effectiveness of rTMS started concomitantly with antidepressant
medications in non-drug-resistant major depressive disorder patients. We also
evaluated if, among the 3 antidepressants administered, one had a better synergy
with rTMS. METHOD: In this 5-week, double-blind, randomized, sham-controlled
study, we recruited 99 inpatients suffering from a major depressive episode
(DSM-IV criteria). They were randomly assigned to receive venlafaxine,
sertraline, or escitalopram in combination with a 2-week period of sham or
active 15-Hz rTMS on the left dorso-lateral prefrontal cortex. Data were
gathered from February 2004 to June 2005. RESULTS: The active rTMS group showed
a significantly faster reduction in Hamilton Rating Scale for Depression (HAM-D)
scores compared with the sham group (p = .0029). The response and remission
rates were significantly greater in the active rTMS group after the stimulation
period (p = .002 and p = .003, respectively), but not at the endpoint. We found
no significant difference in HAM-D score reduction among the 3 drugs
administered, either in the active or in the sham group. CONCLUSION: These
findings support the efficacy of rTMS in hastening the response to
antidepressant drugs in patients with major depressive disorder. The effect of
rTMS seems to be unaffected by the specific concomitantly administered drug.
Publication Types:
Randomized Controlled Trial
PMID: 16401159 [PubMed - indexed for MEDLINE]
J Clin Psychiatry. 2005 Dec;66(12):1524-8.
Long-term maintenance therapy for major depressive disorder with rTMS.
O'Reardon JP, Blumner KH, Peshek AD, Pradilla RR, Pimiento PC.
Department of Psychiatry, University of Pennsylvania, Ste. 4005, 3535 Market
Street, Philadelphia, PA 19104, USA. oreardon@mail.med.upenn.edu
OBJECTIVE: There is growing evidence to support the short-term antidepressant
effects of repetitive transcranial magnetic stimulation (rTMS), but few
published data pertain to the maintenance treatment of patients with
DSM-IV-diagnosed major depressive disorder who have responded acutely to rTMS.
We describe long-term maintenance therapy for major depressive disorder with
rTMS. METHOD: Repetitive transcranial magnetic stimulation was applied in 10
adults over the left prefrontal cortex at 100% of motor threshold, most often at
a frequency of 10 Hz for sessions consisting of 40 trains at 5 seconds per train
(2000 pulses per session), for periods ranging from 6 months to 6 years. Session
frequency averaged 1 to 2 per week. The study was conducted in the TMS lab of an
academic medical center. RESULTS: Seven of the 10 subjects experienced either
marked or moderate benefit, which was sustained without the addition of
concomitant antidepressant medication in 3 cases. There were no serious adverse
events reported by any participant. The seizure rate for the 1831 reported rTMS
sessions was zero. CONCLUSIONS: These data, while open label, suggest that
maintenance rTMS may be a safe and effective treatment modality in some patients
with unipolar depression. Further research into the long-term safety and
efficacy of rTMS is warranted.
Publication Types:
Case Reports
Clinical Trial
Randomized Controlled Trial
PMID: 16401152 [PubMed - indexed for MEDLINE]
Int J Neuropsychopharmacol. 2005 Nov 23;:1-14 [Epub ahead of print]
Predictors of antidepressant response in clinical trials of transcranial
magnetic stimulation.
Fregni F, Marcolin MA, Myczkowski M, Amiaz R, Hasey G, Rumi DO, Rosa M,
Rigonatti SP, Camprodon J, Walpoth M, Heaslip J, Grunhaus L, Hausmann A,
Pascual-Leone A.
Harvard Center for Noninvasive Brain Stimulation, Beth Israel Medical Center,
Harvard Medical School, Boston, MA, USA.
Although previous clinical trials have suggested that repetitive transcranial
magnetic stimulation (rTMS) has a significant antidepressant effect, the results
of these trials are heterogeneous. We hypothesized that individual patients'
characteristics might contribute to such heterogeneity. Our aim was to identify
predictors of antidepressant response to rTMS. We pooled data from six separate
clinical trials conducted independently, which evaluated the effects of rapid
rTMS of the left dorsolateral prefrontal cortex in patients with major
depression. We investigated 195 patients with regard to demographic, depression
and treatment characteristics, psychiatric and drug history. Results showed that
age and treatment refractoriness were significant negative predictors of
depression improvement when adjusting these variables to other significant
predictors and confounders. These findings were not confounded by methodological
differences from the six studies, as the results were adjusted for the study
site. In conclusion TMS antidepressant therapy in younger and less
treatment-resistant patients is associated with better outcome.
PMID: 16939662 [PubMed - as supplied by publisher]
Psychiatry Res. 2005 Nov 15;137(1-2):1-10. Epub 2005 Oct 12.
Transcranial magnetic stimulation in treatment-resistant depressed patients: a
double-blind, placebo-controlled trial.
Rossini D, Lucca A, Zanardi R, Magri L, Smeraldi E.
Department of Psychiatry, School of Medicine, Vita-Salute University, San
Raffaele Hospital, via Stamira d'Ancona 20, Milan 20127, Italy.
rossini.david@hsr.it
This 5-week, randomized, double-blind, placebo-controlled trial investigated the
efficacy and tolerability of high frequency repetitive transcranial magnetic
stimulation (rTMS) directed to the left prefrontal cortex in drug-resistant
depressed patients. Fifty-four patients were randomly assigned to receive 10
daily applications of either real or sham rTMS. Subjects assigned to receive
active stimulation were divided into two further subgroups according to the
intensity of stimulation: 80% vs. 100% of motor threshold (MT). At study
completion, the response rates were 61.1% (n=11), 27.8% (n=5) and 6.2% (n=1) for
the 100% MT group, 80% MT group and sham group, respectively. A significant
difference (Pearson chi(2) test) was found between the 100% MT and sham groups,
while the 80% MT group did not differ significantly from the sham group. Between
the two active groups, a marginally significant difference was observed.
Analysis of variance with repeated measures on Hamilton Depression Rating Scale
scores revealed a significantly different decrease over time of depressive
symptomatology among the three treatment groups. Treatment response appeared to
be unrelated to the demographic and clinical characteristics recorded, and on
the whole the technique was well tolerated. The results of this double-blind
trial showed that rTMS may be a useful and safe adjunctive treatment for
drug-resistant depressed patients.
Publication Types:
Randomized Controlled Trial
PMID: 16225930 [PubMed - indexed for MEDLINE]
Neuroreport. 2005 Nov 7;16(16):1839-42.
Effects of repetitive transcranial magnetic stimulation in depression: a
magnetoencephalographic study.
Maihofner C, Ropohl A, Reulbach U, Hiller M, Elstner S, Kornhuber J, Sperling W.
Department of Neurology, University of Erlangen, Nuremberg, Erlangen, Germany.
maihoefner@physiologiel.uni-erlangen.de
Recently, repetitive transcranial magnetic stimulation has evolved as a
potential therapeutic tool to interfere with brain changes associated with
neurological and psychiatric diseases. Little is known about its mode of action,
however. Here, we investigated effects of repetitive transcranial magnetic
stimulation on spontaneous magnetoencephalographic activity in patients with
major depression. Before treatment, depressed patients showed a significant
increase in slow magnetoencephalographic activity (2-6 Hz) over the left
prefrontal cortex, compared with healthy controls. This activity significantly
decreased during 10 days of repetitive transcranial magnetic stimulation,
paralleled by clinical improvement. We conclude that therapeutic repetitive
transcranial magnetic stimulation effects can be mirrored by changes of
spontaneous magnetoencephalographic activity.
Publication Types:
Clinical Trial
PMID: 16237338 [PubMed - indexed for MEDLINE]
J Affect Disord. 2005 Nov;88(3):255-67. Epub 2005 Sep 2.
A review of the efficacy of transcranial magnetic stimulation (TMS) treatment
for depression, and current and future strategies to optimize efficacy.
Loo CK, Mitchell PB.
School of Psychiatry, University of NSW, Psychiatrist, Black Dog Institute and
South Eastern Sydney Illawarra Area Health Service, Australia.
colleen.loo@unsw.edu.au
BACKGROUND: There is a growing interest in extending the use of repetitive
transcranial magnetic stimulation (rTMS) beyond research centres to the
widespread clinical treatment of depression. Thus it is timely to critically
review the evidence for the efficacy of rTMS as an antidepressant treatment.
Factors relevant to the efficacy of rTMS are discussed along with the
implications of these for the further optimization of rTMS. METHOD: Clinical
trials of the efficacy of rTMS in depressed subjects are summarized and
reviewed, focusing mainly on sham-controlled studies and meta-analyses published
to date. RESULTS: There is a fairly consistent statistical evidence for the
superiority of rTMS over a sham control, though the degree of clinical
improvement is not large. However, this data is derived mainly from two-week
comparisons of rTMS versus sham, and evidence suggests greater efficacy with
longer treatment courses. Studies so far have also varied greatly in approaches
to rTMS stimulation (with respect to stimulation site, stimulus parameters etc)
with little empirical evidence to inform on the relative merits of these
approaches. LIMITATIONS: Only studies published in English were reviewed. Many
of the studies in the literature had small sample sizes and different
methodologies, making comparisons between studies difficult. CONCLUSIONS:
Current published studies and meta-analyses have evaluated the efficacy of rTMS
as given in treatment paradigms that are almost certainly suboptimal (e.g of two
weeks' duration). While the data nevertheless supports positive outcomes for
rTMS, there is much scope for the further refinement and development of rTMS as
an antidepressant treatment. Ongoing research is critical for optimizing the
efficacy of rTMS.
Publication Types:
Review
PMID: 16139895 [PubMed - indexed for MEDLINE]
Psychiatry Clin Neurosci. 2005 Aug;59(4):425-32.
Clinical application of single-pulse transcranial magnetic stimulation for the
treatment of depression.
Fujita K, Koga Y.
Kyorin University School of Medicine Department of Neuropsychiatry, Mitaka,
Tokyo, Japan.
Abstract Transcranial magnetic stimulation (TMS) has been recently suggested for
the treatment of patients with major depression. Based on the results of the
authors' pilot study showing a possible antidepressive effect of single-pulse
TMS, a clinical trial was conducted involving patients with major depression.
For the present study single-photon emission computed tomography (SPECT) was
recorded for six of the target patients to study the effects of TMS on the local
blood flow volume. Twenty-three inpatients meeting the Diagnostic and
Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for major
depression were invited to participate in the study. Depressive symptoms were
rated using the Hamilton Rating Scale for Depression (HAM-D). Patients were
given 10 stimuli over the frontal area of both sides for a total of 20 stimuli
in a session. The subjects had daily TMS session for 5 days as an add-on
therapy. In addition, six patients had their quantitative (99m)Tc-ethyl
cysteinate dimer SPECT images measured before and after TMS treatment. Compared
with the value 2 days prior to the start of TMS therapy (24.2 +/- 4.9), the
average HAM-D scale dropped significantly to 15.3 +/- 6.6 on the day after
completion of such therapy. The results of SPECT showed that the regional
cerebral blood flow (rCBF) of the bilateral frontal region had increased in four
out of six patients when comparing before and after treatment. The present study
shows that single-pulse TMS, which is widely used as a neurological test method,
possesses a wide range of antidepressive effects without inducing adverse
reactions. The results suggest that although repetitive TMS is steadily becoming
the mainstay technique today, single-pulse TMS also possesses sufficient
antidepressive effects.
PMID: 16048448 [PubMed - in process]
J Clin Psychiatry. 2005 Jul;66(7):930-937.
Add-On rTMS for Medication-Resistant Depression: A Randomized, Double-Blind,
Sham-Controlled Trial in Chinese Patients.
Su TP, Huang CC, Wei IH.
From the Department of Psychiatry, Taipei Veterans General Hospital (Dr. Su and
Dr. Huang); the Division of Psychiatry, School of Medicine (Dr. Su), and the
Institute of Clinical Medicine (Dr. Huang), National Yang-Ming University; and
the Department of Anatomy and Cell Biology, College of Medicine, National Taiwan
University (Dr. Wei), Taipei, Taiwan.
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been
developed as a novel tool for improving depression by delivering magnetic
stimulation to the brain. However, the apparent effects of rTMS on depression
have been varied in different studies. The aims of this study were to determine
whether left dorsolateral prefrontal cortex rTMS can alleviate
medication-resistant depression in Chinese patients and to investigate what
demographic variables or clinical features may predict better response. METHOD:
We designed a 2-week randomized, double-blind, sham-controlled study of add-on
rTMS. A total of 30 medication-resistant patients with DSM-IV major depressive
disorder or bipolar disorder, depressed episode completed 10 sessions of active
or sham rTMS-10 patients at each of 2 frequencies, faster (20 Hz) or slower (5
Hz) at 100% motor threshold, and 10 patients at sham stimulation. RESULTS:
Patients at both stimulation frequencies demonstrated a superior reduction of
depression severity compared to sham stimulation (active = 55.7% vs. sham =
16.3%). The response rate for active rTMS was 60%, in contrast to 10% for the
sham treatment. No difference in clinical response was observed between 5 Hz and
20 Hz active rTMS. Clinical variables showed that younger age and less severe
depression at entry may predict the clinical response to rTMS. Except for 1
patient in which rTMS appeared to induce mania, this procedure posed no safety
problem. CONCLUSIONS: To our knowledge, this is the first study to demonstrate
the clinical efficacy and safety of rTMS in Chinese patients. Since not all the
rTMS trials in previous reports had positive results, further larger trials are
still warranted.
PMID: 16013911 [PubMed - as supplied by publisher]
Med J Aust. 2005 Jun 20;182(12):627-32.
Effectiveness of treatments for depression in older people.
Frazer CJ, Christensen H, Griffiths KM.
Centre for Mental Health Research, Australian National University, Canberra, ACT
0200, Australia. cathy.frazer@anu.edu.au.
OBJECTIVE: To conduct a systematic review of the evidence for the effectiveness
of a range of possible treatments for depression in older people. DATA SOURCES:
Literature search using the PubMed, PsycInfo and Cochrane Library databases.
DATA SYNTHESIS: Treatments that have been suggested to be effective for
depression were grouped under three categories: medical treatments,
psychological treatments, and lifestyle changes/alternative treatments. We
describe each treatment, review the studies of its effectiveness in people aged
>/= 60 years, and give a rating of the level of evidence. CONCLUSIONS: The
treatments with the best evidence of effectiveness are antidepressants,
electroconvulsive therapy, cognitive behaviour therapy, psychodynamic
psychotherapy, reminiscence therapy, problem-solving therapy, bibliotherapy (for
mild to moderate depression) and exercise. There is limited evidence to support
the effectiveness of transcranial magnetic stimulation, dialectical behaviour
therapy, interpersonal therapy, light therapy (for people in nursing homes or
hospitals), St John's wort and folate in reducing depressive symptoms.
PMID: 15963019 [PubMed - in process]
Nurs Stand. 2005 May 25-31;19(37):49-50.
Transcranial magnetic stimulation for patients with depression.
Tredget J, Kirov G, Dunn E.
Mood Disorders Service, Wales College of Medicine, Cardiff. tredgetj@cf.ac.uk
Transcranial magnetic stimulation (TMS) is a relatively new technique which has
been used to treat depression. It delivers magnetic radiation to the head using
a hand-held coil. Some studies have indicated clinical remission of depressive
symptomatology with use of TMS. Methodological limitations remain, however, and
more studies are recommended to determine its efficacy.
Publication Types:
Review
Review, Tutorial
PMID: 15938414 [PubMed - indexed for MEDLINE]
Clin Neurophysiol. 2005 May;116(5):1062-71.
Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency:
an efficacious therapy for major drug-resistant depression?
Miniussi C, Bonato C, Bignotti S, Gazzoli A, Gennarelli M, Pasqualetti P, Tura
GB, Ventriglia M, Rossini PM.
IRCCS San Giovanni di Dio-FBF, Brescia, Italy. c.miniussi@oh-fbf.it
OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is proposed for
the treatment of drug-resistant depression. Studies performed in accordance with
evidence-based medicine (EBM) are scarce, particularly in seeking optimal
treatment and evaluation parameters. We aimed to test various types of rTMS in a
large sample of depressed patients following EBM rules and to investigate
treatment-related changes in plasma levels of neurotransmitters involved in
depression. METHODS: Seventy-one drug-resistant depressed patients were randomly
assigned to low (1 Hz) or high (17 Hz) rate TMS, applied for 5 days over the
left dorsolateral prefrontal cortex (L-DLPFC). Patients were separated into two
study designs. One group (20 patients) received only active treatment, while the
other entered a double-blind, placebo-controlled, crossover design. Pre- and
post-treatment blood samples were taken for evaluation of plasma levels of
dopamine and serotonin. RESULTS: After a week of treatment patients had a
measurable benefit. However, overall the placebo stimulation did not differ
significantly from real stimulation, nor were differences observed between the
two rates of rTMS. The only difference emerged when the real stimulation was
applied at 17 Hz following placebo treatment. Plasma levels of neurotransmitters
between active and placebo rTMS were similar. CONCLUSIONS: Using the treatment
schedule of 1 week, although a clinical improvement after active treatment was
indeed observed, this was both clinically and biochemically indistinguishable
from that seen in the placebo arm. SIGNIFICANCE: This suggests that most of the
previous emphasis, for short period of treatment, should be tempered down and
that further work is required in order to verify whether optimal stimulation and
evaluation parameters for TMS-treatment of depression beyond the placebo effect
may be found following EBM rules.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15826846 [PubMed - indexed for MEDLINE]
Dtsch Med Wochenschr. 2005 Apr 8;130(14):889-92.
[A new method for the treatment of depression: repetitive transcranial magnetic
stimulation]
[Article in German]
Cordes J, Mobascher A, Arends M, Agelink MW, Klimke A.
Klinik und Poliklinik fur Psychiatrie und Psychotherapie der
Heinrich-Heine-Universitat Dusseldorf. cordes@uni-duesseldorf.de
Recent data suggest that repetitive transcranial magnetic stimulation (rTMS) is
effective in treating depressive symptoms to a lesser extent compared with
classical electroconvulsive therapy. However, rTMS represents an economical and
well tolerable procedure in relation to the expenditure of electroconvulsive
therapy with anaesthesia. Usually, rTMS is applicated as an add-on-therapy
accompanying psychopharmacological treatment. So far, it has predominantly been
used for patients with long-standing and so called treatment-refractory
symptoms. However, even in the early phase of a depressive episode rTMS would be
possibly more effective. In many cases, the standard procedure-application of up
to 10 rTMS-sessions will not be enough to produce therapeutic benefit. Therefore
rTMS series including up to 20 sessions are recommended. Long-term studies are
needed to clarify the role of rTMS for relapse prevention and to determine the
optimal frequency and duration of rTMS in such an indication. Although numerous
results of newer studies suggest a moderate antidepressive effect of rTMS, its
application in daily clinical routine practice cannot be recommended yet.
Larger, accurate designed and controlled studies, especially involving patients
of old age, are needed to evaluate the true tolerability and effectiveness of
rTMS as a new treatment option for depressive symptoms.
PMID: 15800823 [PubMed - indexed for MEDLINE]
J Psychiatry Neurosci. 2005 Mar;30(2):91-7.
Comment in:
J Psychiatry Neurosci. 2005 Mar;30(2):81-2.
A framework for targeting alternative brain regions with repetitive transcranial
magnetic stimulation in the treatment of depression.
Schutter DJ, van Honk J.
Affective Neuroscience Section, Helmholtz Research Institute, Utrecht
University, Utrecht, The Netherlands. d.schutter@fss.uu.nl
It has been argued that clinical depression is accompanied by reductions in
cortical excitability of the left prefrontal cortex (PFC). In support of this,
repetitive transcranial magnetic stimulation (rTMS), which is a method of
enhancing cortical excitability, has shown antidepressant efficacy when applied
over the left PFC, although the overall therapeutic effects remain inconclusive.
The cerebral pathophysiology of depression is, however, not limited to
dysfunctions in the PFC, thus, targeting alternative brain regions with rTMS may
provide new therapeutic windows in the treatment of depression. Evidence from
electroencephalography and lesion studies suggests that not only is the left PFC
involved in depression but also the parietal cortex and cerebellum. Furthermore,
rTMS over the parietal cortex and the cerebellum has been found to improve mood
and emotional functioning, at least in healthy volunteers. We have integrated
these findings in an rTMS-oriented theoretical framework for the neurobiology of
low mood and depression. To establish the possible therapeutic efficacy of this
model, whereby, for example, the application of slow rTMS over the right
parietal cortex and fast rTMS over the cerebellum may be beneficial in different
subtypes of depression, clinical rTMS studies that target the parietal cortex
and cerebellum are warranted.
Publication Types:
Review
PMID: 15798784 [PubMed - indexed for MEDLINE]
J Psychiatry Neurosci. 2005 Mar;30(2):83-90.
Comment in:
J Psychiatry Neurosci. 2005 Mar;30(2):81-2.
Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the
treatment of depression: a systematic review and meta-analysis.
Couturier JL.
Department of Psychiatry, University of Western Ontario, London, Ont.
jlcoutur@uwo.ca
OBJECTIVE: To systematically review the literature pertaining to rapid-rate
repetitive transcranial magnetic stimulation (rTMS) compared with sham therapy
for the treatment of a major depressive episode in order to arrive at
qualitative and quantitative conclusions about the efficacy of rapid-rate rTMS.
METHODS: MEDLINE, the Cochrane Library, the metaRegister of Controlled Trials
and abstracts from scientific meetings were searched for the years 1966 until
July 2003. The search terms "transcranial magnetic stimulation" and
"transcranial magnetic stimulation AND depression" were used. Eighty-seven
randomized controlled trials investigating the efficacy of rTMS were referenced
on MEDLINE. Nineteen of these involved treatment of a major depressive episode,
and these were reviewed. Six met more specific inclusion criteria including the
use of rapid-rate stimulation, application to the left dorsolateral prefrontal
cortex, evaluation with the 21-item Hamilton Rating Scale for Depression (HAM-D)
and use of an intent-to-treat analysis. Scores on the 21-item HAM-D after
treatment and standard deviations were extracted from each article for treatment
and control subjects. A random-effects model was chosen for the meta-analysis,
and the weighted mean difference was used as a summary measure. RESULTS: Six
studies that met the inclusion criteria were identified and included in the
meta-analysis. Two of these reported a significantly greater improvement in mood
symptoms in the treatment versus the sham group. When combined in the
meta-analysis, the overall weighted mean difference was -1.1 (95% confidence
interval -4.5 to 2.3), and the results of a test for heterogeneity were not
significant (chi2(5) = 5.81, p = 0.33). CONCLUSIONS: This meta-analysis suggests
that rapid-rate rTMS is no different from sham treatment in major depression;
however, the power within these studies to detect a difference was generally
low. Randomized controlled trials with sufficient power to detect a clinically
meaningful difference are required.
Publication Types:
Meta-Analysis
Review
PMID: 15798783 [PubMed - indexed for MEDLINE]
J Neurol Neurosurg Psychiatry. 2005 Apr;76(4):527-33.
Mirtazapine increases cortical excitability in healthy controls and epilepsy
patients with major depression.
Munchau A, Langosch JM, Gerschlager W, Rothwell JC, Orth M, Trimble MR.
Sobell Department of Motor Neuroscience and Movement Disorders, Dept. of
Clinical and Experimental Epilepsy, Institute of Neurology, National Hospital
for Neurology and Neurosurgery, Queen Square, London, UK.
Muenchau@uke.uni-hamburg.de
BACKGROUND: Epilepsy is often complicated by depression requiring antidepressant
treatment. Such treatment might be proconvulsive. OBJECTIVE: To examine the
effects of the noradrenergic and specific serotonergic antidepressant
mirtazapine on motor cortex excitability in epilepsy patients with depression
and in healthy controls, using transcranial magnetic stimulation (TMS). METHODS:
Seven clinically depressed epilepsy patients treated with anticonvulsant drugs
and six healthy volunteers were studied. Before intake of mirtazapine and 24
hours afterwards (and also three weeks afterwards in the patients), the active
and resting motor threshold (AMT, RMT), the size of the motor evoked potential
(MEP), the cortical silent period (SP), and intracortical
inhibition/facilitation and intracortical facilitatory I wave interactions were
determined using single and paired pulse TMS. RESULTS: At baseline, AMT and RMT
were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP
area greater in patients (p = 0.041). In patients but not in healthy subjects
AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had
no significant effect on the MEP size, duration of the SP, or the ratio of SP
duration to MEP size in patients. The duration of the SP was longer (p = 0.037)
but the ratio of SP duration to MEP size remained similar in healthy subjects
after mirtazapine. There were no significant differences in paired pulse
measures between the two groups either at baseline or after mirtazapine.
CONCLUSIONS: Mirtazapine increased neuronal excitability of pyramidal tract
axons in an activated state in both healthy controls and epilepsy patients with
major depression.
PMID: 15774440 [PubMed - indexed for MEDLINE]
Health Technol Assess. 2005 Mar;9(9):1-156, iii-iv.
Clinical and cost-effectiveness of electroconvulsive therapy for depressive
illness, schizophrenia, catatonia and mania: systematic reviews and economic
modelling studies.
Greenhalgh J, Knight C, Hind D, Beverley C, Walters S.
Nuffield Institute for Health, University of Leeds, UK.
OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of
electroconvulsive therapy (ECT) for depressive illness, schizophrenia, catatonia
and mania. DATA SOURCES: Electronic bibliographic databases. The reference lists
of relevant articles and health services research-related resources were
consulted via the Internet. REVIEW METHODS: Identified studies were examined to
ascertain whether they met the inclusion criteria for the review. The study
quality of relevant articles was assessed using standard checklists and data
were abstracted using standardised forms into a database. Where relevant,
results from studies were pooled for meta-analysis. Two economic models were
developed primarily based on evidence from the clinical effectiveness analysis
and limited quality of life studies. RESULTS: Two good-quality systematic
reviews of randomised evidence of the efficacy and safety of ECT in people with
depression, schizophrenia, catatonia and mania were identified. Four systematic
reviews on non-randomised evidence were also identified, although only one of
these could be described as good quality. There was no randomised evidence of
the effectiveness of ECT in specific subgroups including older people, children
and adolescents, people with catatonia and women with postpartum exacerbations
of depression or schizophrenia. The economic modelling results for depression
did not demonstrate that any of the scenarios had a clear economic benefit over
the others, mainly because of the uncertainty surrounding the clinical
effectiveness of the different treatments and the quality of life utility gains.
Sensitivity analysis surrounding the cost of ECT and the quality of life utility
values had little effect on the overall results. The results of the model for
schizophrenia adapted to include ECT suggest that clozapine is a cost-effective
treatment compared with ECT. For patients who fail to respond to clozapine, ECT
treatment may be preferred to the comparative treatment of
haloperidol/chlorpromazine. CONCLUSIONS: Real ECT is probably more effective
than sham ECT, but as stimulus parameters have an important influence on
efficacy, low-dose unilateral ECT is no more effective than sham ECT. ECT is
probably more effective than pharmacotherapy in the short term and limited
evidence suggests that ECT is more effective than repetitive transcranial
magnetic stimulation. Tricyclic antidepressants (TCAs) may improve the
antidepressant effect of ECT during the course of treatment. Continuation
pharmacotherapy with TCAs combined with lithium in people who have responded to
ECT reduces the rate of relapses. Overall, gains in the efficacy of the
intervention depending on the stimulus parameters of ECT are achieved only at
the expense of an increased risk of cognitive side-effects. Limited evidence
suggests these effects do not last beyond 6 months, but there is no evidence
examining the longer term cognitive effects of ECT. There is little evidence of
the long-term efficacy of ECT. ECT either combined with antipsychotic medication
or as a monotherapy is not more effective than antipsychotic medication in
people with schizophrenia. More research is needed to examine the long-term
efficacy of ECT and the effectiveness of post-ECT pharmacotherapy, the
short-term and longer term cognitive side-effects of ECT, and the impact of ECT
on suicide and all-cause mortality. Further work is needed to examine the
information needs of people deciding whether to accept ECT and how their
decision-making can be facilitated. More research is also needed on the
mechanism of action of ECT. Finally, the quality of reporting of trials in this
area would be vastly improved by strict adherence to the Consolidated Standards
of Reporting Trials recommendations. Economic analysis may identify areas in
which research would be best targeted by identifying parameters where reducing
the level of uncertainty would have the most effect in helping to make the
decision on whether ECT is a cost-effective treatment.
Publication Types:
Review
PMID: 15774232 [PubMed - indexed for MEDLINE]
Curr Pain Headache Rep. 2005 Apr;9(2):87-9.
Transcranial magnetic stimulation for central pain.
Canavero S, Bonicalzi V.
Turin Advanced Neuromodulation Group, Via Morazzone 21,Torino 10132, Italy.
solara@infinito.it
Transcranial magnetic stimulation recently has emerged as a therapeutic tool in
neurology and psychiatry, with contradictory results. Central pain, a major
chronic pain syndrome affecting millions of people worldwide, has been the focus
of a few studies. Although transcranial magnetic stimulation has no role in the
chronic management of such pain, it has potential as a screening procedure for
the much more effective extradural cortical stimulation, a minimally invasive
neurosurgical procedure that has emerged as the technique of choice in treating
these patients.
Publication Types:
Review
Review, Tutorial
PMID: 15745616 [PubMed - indexed for MEDLINE]
Australas Psychiatry. 2004 Sep;12(3):234-8.
Repetitive transcranial magnetic stimulation and electroconvulsive therapy:
complementary or competitive therapeutic options in depression?
Fitzgerald P.
Alfred Psychiatry Research Centre, Alfred and Monash University Department of
Psychological Medicine, Vic., Australia. paul.fitzgerald@med.monash.edu.au
OBJECTIVE: To examine issues pertaining to the potential clinical roles of
repetitive transcranial magnetic stimulation (rTMS) and the relationship of
these to the use of electroconvulsive therapy (ECT). METHODS: A review of
studies was carried out comparing the use of rTMS and ECT, with consideration of
issues relating to the populations in which rTMS may be applied. RESULTS: There
have been a number of randomized comparisons of rTMS and ECT. There are
limitations with these studies, but in general they indicate that in
non-psychotic patients rTMS appears to have a similar rate of response to ECT
and certainly seems to have meaningful clinical effects. There are a number of
clinical subpopulations in whom rTMS, but not ECT, is suitable, and assessment
of the effectiveness of TMS in these populations is required. CONCLUSIONS:
Repetitive TMS and ECT are likely to prove to be complementary clinical tools
and the introduction of clinical programmes with rTMS will enhance patient
options rather than replace the use of ECT.
PMID: 15715781 [PubMed - indexed for MEDLINE]
Neuropsychopharmacology. 2005 Jun;30(6):1181-6.
Plasma concentrations of neuroactive steroids before and after electroconvulsive
therapy in major depression.
Baghai TC, di Michele F, Schule C, Eser D, Zwanzger P, Pasini A, Romeo E,
Rupprecht R.
Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of
Munich, Munich, Germany.
There is evidence that both cerebrospinal fluid (CSF) and plasma concentrations
of 3alpha-reduced neuroactive steroids are decreased in major depressive
disorder. Successful antidepressant pharmacotherapy, for example, with selective
serotonin reuptake inhibitors (SSRIs), over several weeks is accompanied by an
increase in CSF and plasma concentrations of these neuroactive steroids.
However, no such increase has been observed during nonpharmacological treatments
such as partial sleep deprivation or repetitive transcranial magnetic
stimulation. In order to investigate whether concentration changes in
neuroactive steroids are an important component of clinically effective
antidepressant treatment, we examined plasma concentrations of the neuroactive
steroids 3alpha,5alpha-tetrahydroprogesterone,
3alpha,5beta-tetrahydroprogesterone, 3beta,5alpha-tetrahydroprogesterone, and
their precursors progesterone, 5alpha-dihydroprogesterone, and
5beta-dihydroprogesterone in 31 pharmacotherapy-resistant depressed in-patients
before and after unilateral electroconvulsive therapy (ECT) as a monotherapy
over 4 weeks. Samples were quantified for neuroactive steroids by means of a
highly sensitive and specific combined gas chromatography/mass spectrometry
analysis. In all, 51.6% of the patients were treatment responders. There was no
influence of ECT on the plasma concentrations of any neuroactive steroid
studied. Moreover, neuroactive steroid levels did not differ between treatment
responders and nonresponders. Our study shows that changes in neuroactive
steroid plasma levels are not a mandatory factor for successful antidepressant
treatment by ECT. Thus, the previously observed changes in plasma concentrations
of neuroactive steroids following treatment with antidepressants such as SSRIs
more likely reflect distinct pharmacological properties of these compounds
rather than clinical improvement.
Publication Types:
Clinical Trial
PMID: 15702138 [PubMed - indexed for MEDLINE]
Psychol Med. 2004 Oct;34(7):1157-63.
High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a
combined treatment and neuroimaging study.
Hajak G, Marienhagen J, Langguth B, Werner S, Binder H, Eichhammer P.
Department of Psychiatry and Psychotherapy, University of Regensburg,
Regensburg, Germany. goeran.hajak@medbo.de
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of frontal brain
regions is under study as a non-invasive method in the treatment of affective
disorders. Recent publications provide increasing evidence that rTMS may be
useful in treating schizophrenia. Results are most intriguing, demonstrating a
reduction of negative symptoms following high-frequency rTMS. In this context,
disentangling of negative and depressive symptoms is of the utmost importance
when understanding specific rTMS effects on schizophrenic symptoms. METHOD:
Using a sham-controlled parallel design, 20 patients with schizophrenia were
included in the study. Patients were treated with high-frequency 10 Hz rTMS over
10 days. Besides clinical ratings, ECD-SPECT (technetium-99 bicisate single
photon emission computed tomography) imaging was performed before and after
termination of rTMS treatment. RESULTS: High-frequency rTMS leads to a
significant reduction of negative symptoms combined with a trend for
non-significant improvement of depressive symptoms in the active stimulated
group as compared with the sham stimulated group. Additionally, a trend for
worsening of positive symptoms was observed in the actively treated
schizophrenic patients. In both groups no changes in regional cerebral blood
flow could be detected by ECD-SPECT. CONCLUSIONS: Beneficial effects of
high-frequency rTMS on negative and depressive symptoms were found, together
with a trend for worsening positive symptoms in schizophrenic patients.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15697042 [PubMed - indexed for MEDLINE]
Nervenarzt. 2005 Jan;76(1):28-35.
[Vagus nerve stimulation, repetitive transcranial magnetic stimulation, and
electroconvulsive therapy in the treatment of depressive disorders]
[Article in German]
Bajbouj M, Heuser I.
Klinik und Poliklinik fur Psychiatrie und Psychotherapie,
Charite-Universitatsmedizin Berlin. malek.bajbouj@charite.de
Affective disorders, especially major depression, are the most common
psychiatric disorders. Although well treatable, a number of patients do not or
do not sufficiently respond to antidepressant pharmacotherapy. Therefore there
is a need for safe and efficient alternative therapeutic strategies.
Neurostimulatory therapies such as electroconvulsive therapy, repetitive
transcranial magnetic stimulation, and vagus nerve stimulation belong to these
alternatives. In this article we review their mechanisms of action and summarize
efficacy and adverse effects.
PMID: 15666168 [PubMed - indexed for MEDLINE]
Clin Neurophysiol. 2005 Feb;116(2):386-92.
Effect of electroconvulsive therapy on cortical excitability in patients with
major depression: a transcranial magnetic stimulation study.
Chistyakov AV, Kaplan B, Rubichek O, Kreinin I, Koren D, Hafner H, Feinsod M,
Klein E.
Laboratory of Clinical Neurosciences, Department of Neurosurgery, Rambam
(Maimonides) Medical Center, B. Rappaport Faculty of Medicine, The Technion,
Israel Institute of Technology, Haifa, Israel. a_chistyakov@rambam.health.gov.il
OBJECTIVE: The antidepressant action of electro-convulsive therapy (ECT) and
repetitive transcranial magnetic stimulation (rTMS) may be related to their
ability to modulate cortical excitability. The aim of this study was to
investigate changes in cortical excitability following ECT in patients with
major depression (MD) and to compare therapeutic efficacy of ECT combined with
rTMS to that of ECT alone. METHODS: Twenty-two patients with MD were assigned to
receive ECT and right prefrontal 1 Hz rTMS (n=12) or ECT with sham rTMS (n=10).
ECT was given twice weekly and rTMS was applied on the remaining 4 days,
throughout 3 weeks. The resting motor threshold (rMT) and motor evoked potential
(MEP)/M-wave area ratio were evaluated before and 6 h after the first, third and
sixth ECT session. The active motor threshold (aMT), intra-cortical inhibition
(ICI) and intra-cortical facilitation (ICF) were measured at baseline and 24 h
after the last ECT. RESULTS: There were no significant differences in the degree
of clinical improvement and measures of cortical excitability in the ECT+active
rTMS group as compared to the ECT+sham rTMS group. Marked clinical improvement
observed in 19 out of the 22 patients was associated with a significant increase
of the MEP/M-wave area ratio, decrease of the aMT and reduction of the ICI in
the left hemisphere. CONCLUSIONS: The antidepressant effect of ECT was
associated with an enhancement of left hemispheric excitability. rTMS did not
add to the beneficial effect of ECT. However, the small sample size and the
robust effect of ECT might have obscured a potential therapeutic effect of rTMS.
SIGNIFICANCE: Measures of cortical excitability may provide insight to our
understanding of the mechanism of action of ECT and might be useful for the
assessment of treatment response.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 15661116 [PubMed - indexed for MEDLINE]
Biol Psychiatry. 2005 Jan 15;57(2):162-6.
Transcranial magnetic stimulation accelerates the antidepressant effect of
amitriptyline in severe depression: a double-blind placebo-controlled study.
Rumi DO, Gattaz WF, Rigonatti SP, Rosa MA, Fregni F, Rosa MO, Mansur C,
Myczkowski ML, Moreno RA, Marcolin MA.
Institute of Psychiatry, University of Sao Paulo, Faculty of Medicine, Sao
Paulo-SP, Brazil. drumi@usp.br
BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive method to
stimulate the cortex, and the treatment of depression is one of its potential
therapeutic applications. Three recent meta analyses strongly suggest its
benefits in the treatment of depression. The present study investigates whether
repetitive TMS (rTMS) accelerates the onset of action and increases the
therapeutic effects of amitriptyline. METHODS: Forty-six outpatients meeting
DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to
receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over
dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial.
All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The
rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of
motor threshold and 1250 pulses per session). Sham stimulation followed the same
schedule, however, using a sham coil. The efficacy variables were the Hamilton
Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression
Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global
Impression (CGI). Tolerability was assessed by clinical examination and a safety
screening of TMS side effects. RESULTS: Repetitive TMS had a significantly
faster response to amitriptyline. There was a significant decrease in HAM-D/17
scores, already after the first week of treatment (p < .001 compared with
baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in
the rTMS group was significantly superior compared with the sham group
throughout the study (p < .001 at fourth week). CONCLUSIONS: Repetitive TMS at 5
Hz accelerated the onset of action and augmented the response to amitriptyline.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15652875 [PubMed - indexed for MEDLINE]
Bull Acad Natl Med. 2004;188(6):999-1007; discussion 1007-10.
[Depression and aging]
[Article in French]
Loo H, Gallarda T, Fabre I, Olie JP.
Service Hospitalo-Universitaire de Sante Mentale et de Therapeutique, CH
Sainte-Anne, 1 rue Cabanis, 75674 Paris 14.
Depression is one of the most common health disorders in elderly people. It is
still often considered as a natural consequence of aging, arising in reaction to
a medical disease, cognitive or functional decline, or a loss of social fabric.
Many studies have highlighted the low rates of diagnosis and treatment of
depression, especially in the primary care setting. Major depression in old age
is characterized by the same core symptoms as in other periods of life. However,
aging may accentuate some symptoms and alleviate others. Somatic concern, marked
anxiety, poor subjective memory, psychotic ideation, and recurrent thoughts of
death can mask sadness and anhedonia. Organic factors and adverse life events
are often intricately linked with the pathogenesis of depressive states in the
elderly. The role of cerebrovascular lesions has also been established,
particularly in late-onset depressive disorders. The management of depressive
disorders in older people, as in younger adults, involves pharmacological and
psychological treatments. Electroconvulsive therapy can be beneficial in some
cases. Transcranial magnetic stimulation is being evaluated in this setting.
Publication Types:
Review
Review, Tutorial
PMID: 15651428 [PubMed - indexed for MEDLINE]
Child Adolesc Psychiatr Clin N Am. 2005 Jan;14(1):193-210, viii-ix.
Electroconvulsive therapy and repetitive transcranial magnetic stimulation in
children and adolescents: a review and report of two cases of epilepsia
partialis continua.
Morales OG, Henry ME, Nobler MS, Wassermann EM, Lisanby SH.
Magnetic Brain Stimulation Laboratory, Department of Biological Psychiatry, New
York State Psychiatric Institute, 1051 Riverside Drive, Box 126, New York, NY
10032-2695, USA. om2102@columbia.edu
Brain stimulation for the treatment of psychiatric disorders has received
increasing attention over the past decade. The introduction of experimental
means to stimulate the brain noninvasively with magnetic fields not only has
raised interest in these novel means of modulating brain activity but also has
refocused attention on a mainstay in the treatment of severe major depression
and other disorders (electroconvulsive therapy). This article reviews the
current state of knowledge concerning the use electroconvulsive therapy,
repetitive transcranial magnetic stimulation, and magnetic seizure therapy in
children and adolescents. Two cases of medically intractable epilepsia partialis
continua are presented to add to the limited literature on the use of repetitive
transcranial magnetic stimulation in children and adolescents and illustrate the
concept of using functional neuroimaging results to target the application of a
focal intervention in an attempt to dampen hyperactive regions of the cortex.
Publication Types:
Case Reports
Review
Review, Tutorial
PMID: 15564059 [PubMed - indexed for MEDLINE]
Child Adolesc Psychiatr Clin N Am. 2005 Jan;14(1):1-19, v.
Emerging brain-based interventions for children and adolescents: overview and
clinical perspective.
Hirshberg LM, Chiu S, Frazier JA.
The NeuroDevelopment Center, 260 West Exchange Street, Suite 302, Providence, RI
02903, USA. lhirshberg@neruodevelopmentcenter.com
Electroencephalogram biofeedback (EBF), repetitive transcranial magnetic
stimulation (rTMS), and vagal nerve stimulation (VNS) are emerging interventions
that attempt to directly impact brain function through neurostimulation and
neurofeedback mechanisms. This article provides a brief overview of each of
these techniques, summarizes the relevant research findings, and examines the
implications of this research for practice standards based on the guidelines for
recommending evidence based treatments as developed by the American Academy of
Child and Adolescent Psychiatry for attention deficit hyperactivity disorder
(ADHD). EBF meets the "Clinical Guidelines" standard for ADHD, seizure
disorders, anxiety, depression, and traumatic brain injury. VNS meets this same
standard for treatment of refractory epilepsy and meets the lower "Options"
standard for several other disorders. rTMS meets the standard for "Clinical
Guidelines" for bipolar disorder, unipolar disorder, and schizophrenia. Several
conditions are discussed regarding the use of evidence based thinking related to
these emerging interventions and future directions.
Publication Types:
Review
Review, Tutorial
PMID: 15564050 [PubMed - indexed for MEDLINE]
Encephale. 2004 Jul-Aug;30(4):363-8.
[Transcranial magnetic stimulation in cognition and neuropsychology]
[Article in French]
Verdon CM, Saba G, Januel D.
Unite de Recherche Clinique Romain-Rolland, EPS Ville-Evrard (Secteur 3), 5, rue
du Docteur Delafontaine, 93200 Saint-Denis.
Classical neuropsychology relies on patients with irreversible brain lesions and
cognitive impairments give informations about normal brain function.
Transcranial Magnetic Stimulation (TMS) is a non-invasive method which involves
placing an electromagnetic coil on the scalp. A pulse generates a magnetic field
and this one passes, unattenuated by the skin and scalp, into the cortex
inducing a current which results in neural activity. The technique shows a good
temporal resolution and, moreover, because it represents an interference
technique, can be said to have excellent functional resolution. For this reason,
TMS appears to be a new tool for research in neuropsychology, producing
transitory 'virtual lesion'effects which could help to understand how, when and
where cognitive tasks are performed. The purpose of this article is to review
recent research using TMS in cognition and neuropsychology, in a non exhaustive
way. In safety studies, single TMS over motor cortex can produce simple
movements. Several groups have applied TMS to the study of visual processing and
found an impaired detection of visual stimuli. In a same way, TMS can disrupt
speech when it was delivered in the language dominant hemisphere. Studies on the
memory effects of TMS have been conflicting and the results seem to depend on
the choice of paradigm and parameters. Other study depicted improvements in
executive functioning after TMS on the left middle frontal gyrus or a diminution
in reaction time during an analogic reasoning task. Moreover, some facial
emotions seem to be less recognizable after TMS. Although TMS seem to be a new
tool for neuro-psychological investigations in healthy subjects, few studies
reported cognitive effects of rTMS treatment in psychiatry. In a therapeutic
view, many of these trials have supported a significant effect of TMS, but in
some studies the effect is small and short lived. Several groups have reported
on the use of rTMS as a treatment in resistant major depression and the impact
on cognition functioning. Most of results tend to find no adverse cognitive
effects after several weeks of daily rTMS in depressed patients, compared to
Electroconvulsivo-therapy (ECT). The effects of transcranial magnetic
stimulation (TMS) on hallucination severity and neurocognition were studied in a
recent study. A statistically significant improvement was observed on a
hallucination scale and on one cognitive measure. TMS is a promising tool for
cognitive neuroscience and can provide complementary information to the one
obtained using neuropsychological tests, and the one obtained using functional
imaging techniques, which have superior spatial but inferior temporal
resolution.
PMID: 15538312 [PubMed - indexed for MEDLINE]
Rev Bras Psiquiatr. 2004 Jun;26(2):100-2. Epub 2004 Oct 27.
[Transcranial Magnetic Stimulation in depression: results of bi-weekly
treatment]
[Article in Portuguese]
Boechat-Barros R, Brasil-Neto JP.
Laboratorio de Neurociencias e Comportamento, Departamento de Ciencias
Fisiologicas, Instituto de Biologia, Universidade de Brasilia, DF, Brazil.
OBJECTIVE: Transcranial Magnetic Stimulation (TMS) has been shown to be a useful
therapy for depression. This paper evaluates the results of bi-weekly
low-frequency TMS of 4 weeks duration, in 10 patients with depression who do not
respond or are intolerant to antidepressive medication. METHODS: This is a case
series study. DMS-IV criteria were used to diagnose depression. In order to
disclose possible improvements in depressive symptoms, the 17 items Hamilton
scale was used at three different moments: at the beginning, middle and end of
the treatment period. Results were analysed using Friedman's chi2 test. RESULTS:
Hamilton's scale score improvement was > 50% in five patients and > 75% in 3 of
these. CONCLUSIONS: TMS may be efficacious, safe and easily performed as an
adjunct to medical treatment of depression. We cannot differentiate a
potentiation of the effect of antidepressive medication from an intrinsic effect
of TMS alone, since we did not treat any subjects without the concurrent use of
medication.
PMID: 15517060 [PubMed - in process]
J Clin Psychiatry. 2004 Oct;65(10):1323-8.
Comment in:
J Clin Psychiatry. 2005 Apr;66(4):543; author reply 543-4.
A 3-month, follow-up, randomized, placebo-controlled study of repetitive
transcranial magnetic stimulation in depression.
Koerselman F, Laman DM, van Duijn H, van Duijn MA, Willems MA.
Department of Psychiatry, St. Lucas Andreas Hospital, Amsterdam, The
Netherlands. f.koerselman@slaz.nl
BACKGROUND/OBJECTIVE: There is evidence for an antidepressant effect of
repetitive transcranial magnetic stimulation (rTMS), but little is known about
posttreatment course. Therefore, we conducted a placebo-controlled, double-blind
study in depressed patients in order to investigate the effect of rTMS on
depression over 12 weeks after completion of the 2-week stimulation period.
METHOD: 55 patients with a moderate or severe DSM-IV major depressive episode
were randomly assigned to rTMS or sham treatment. rTMS was given daily for 10
days over the left dorsolateral prefrontal cortex with the following treatment
parameters: 20 Hz, 20 trains of 2 seconds, 30 seconds between trains, and 80%
motor threshold. The effect of rTMS on depression was rated repeatedly with the
17-item Hamilton Rating Scale for Depression (HAM-D) during the 2-week period of
stimulation and the 12-week follow-up period conducted from 1997 to 2001.
RESULTS: We found a modest, clinically nonrelevant decrease in HAM-D scores in
both rTMS and sham patients over 2 weeks of treatment. However, over the
subsequent 12-week follow-up, the rTMS group continued to improve significantly
compared with the placebo group. CONCLUSION: Decrease of depressive symptoms may
continue after the cessation of rTMS stimulation.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15491234 [PubMed - indexed for MEDLINE]
J Affect Disord. 2004 Oct 1;82(1):71-6.
Motor cortical excitability and clinical response to rTMS in depression.
Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, de Castella A, Bradshaw JL,
Kulkarni J.
Alfred Psychiatry Research Center, The Alfred and Monash University, Department
of Psychological Medicine, Level 2, Old Baker Building, Commercial Road,
Melbourne, Vic. 3004, Australia. paul.fitzgerald@med.monash.edu.au
BACKGROUND: The relationship between frontal lobe activity in the left and right
hemispheres and the pathophysiology of depression remains unclear. In addition,
it is uncertain whether levels of frontal or motor cortical excitability relate
to clinical response to treatment modalities. We aimed to explore whether motor
cortical excitability as assessed with single and paired pulse transcranial
magnetic stimulation (TMS) could be used to predict the response to treatment
with repetitive TMS (rTMS) applied to the left or right prefrontal cortex.
METHODS: Motor thresholds, cortical excitability and cortical inhibition (CI)
were assessed prior to a trial of rTMS in patients with treatment resistant
depression. RESULTS: There was no consistent pattern of differences in
hemispheric activity, although there was a relationship between the degree of
psychopathology and cortical excitability (right hemisphere) and an inverse
relationship between inhibitory activity and clinical response (left
hemisphere). CONCLUSIONS: The study does not support a simple model of
laterality in motor cortical excitability in depression. The TMS measures used
in this study appear to be of limited use in the prediction of clinical response
to rTMS.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15465578 [PubMed - indexed for MEDLINE]
Schizophr Res. 2004 Nov 1;71(1):1-16.
Transcranial Magnetic Stimulation in the investigation and treatment of
schizophrenia: a review.
Haraldsson HM, Ferrarelli F, Kalin NH, Tononi G.
Department of Psychiatry, University of Wisconsin, 6001 Research Park Blvd.,
Madison, WI 53719, USA. hmagnus@landspitali.is
Transcranial Magnetic Stimulation (TMS) is a non-invasive method of stimulating
the brain that is increasingly being used in neuropsychiatric research and
clinical psychiatry. This review examines the role of TMS in schizophrenia
research as a diagnostic and a therapeutic resource. After a brief overview of
TMS, we describe the application of TMS to schizophrenia in studies of cortical
excitability and inhibition, and we discuss the potential confounding role of
neuroleptic medications. Based on these studies, it appears that some impairment
of cortical inhibition may be present in schizophrenic subjects. We then review
attempts to employ TMS for treating different symptoms of schizophrenia. Some
encouraging results have been obtained, such as the reduction of auditory
hallucinations after slow TMS over auditory cortex and an improvement of
psychotic symptoms after high frequency TMS over left prefrontal cortex.
However, these results need to be confirmed using better placebo conditions.
Future studies are likely to employ TMS in combination with functional brain
imaging to examine the effects produced by the stimulated area on activity in
other brain regions. Such studies may reveal impaired effective connectivity
between specific brain areas, which could identify these regions as targets for
selective stimulation with therapeutic doses of TMS.
Publication Types:
Review
PMID: 15374567 [PubMed - indexed for MEDLINE]
Eur Psychiatry. 2004 Sep;19(6):382-3.
Repetitive transcranial magnetic stimulation does not potentiate antidepressant
treatment.
Poulet E, Brunelin J, Boeuve C, Lerond J, D'Amato T, Dalery J, Saoud M.
EA 3092, Universite Claude Bernard Lyon 1, 69677 Bron cedex, France.
In a double blind controlled study, rTMS results in a similar antidepressant
effect to sham in combination with paroxetine. Both groups had the same delay in
scale's scores improvement. rTMS seems not to be efficient as an add-on
treatment to pharmacological medication in non-resistant major depression.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15363481 [PubMed - indexed for MEDLINE]
Int J Geriatr Psychiatry. 2004 Sep;19(9):833-42.
Antidepressant efficacy and cognitive effects of repetitive transcranial
magnetic stimulation in vascular depression: an open trial.
Fabre I, Galinowski A, Oppenheim C, Gallarda T, Meder JF, De Montigny C, Olie
JP, Poirier MF.
Sainte-Anne Hospital, University Department of Psychiatry, Paris, France.
BACKGROUND: Beneficial effects of repetitive transcranial magnetic stimulation
(rTMS) were demonstrated by many controlled studies in major depression.
Moreover, this promising and non invasive therapeutic tool seems to be better
tolerated than electroconvulsive therapy.Vascular depression is a subtype of
late-life depression, associated with cerebrovascular disease and means a poorer
response to antidepressant treatment. We employed rTMS over the left prefrontal
cortex in 11 patients with late-onset resistant vascular depression. The primary
purpose of this two-week open study was to examine antidepressant efficacy of
rTMS in vascular depression. The secondary aim was to evaluate cognitive effects
of rTMS in our sample. METHODS: Clinical status, as measured with the Hamilton
Depression Rating Scale (HDRS), and cognitive effects, as evaluated by
neuropsychological tests, were assessed at baseline and after two weeks of rTMS.
Brain measurements to obtain an index of prefrontal atrophy were performed at
both the motor cortex and prefrontal cortex. RESULTS: Five out of 11 resistant
patients with late-onset vascular depression were responders. They showed a
clinically meaningful improvement in HDRS scores, with a decrease of 11, 4
points (p<0.01). Antidepressant response is correlated to the relative degree of
prefrontal atrophy (p = 0.05). After two weeks, verbal fluency and visuospatial
memory improved. No cognitive performance deteriorated except for verbal memory,
as the delayed recall decreased significantly in the responders' group.
CONCLUSIONS: Our preliminary observations prompt to perform a subsequent
controlled study to examine if rTMS may constitute an alternative to
electroconvulsive therapy.
Publication Types:
Clinical Trial
PMID: 15352140 [PubMed - indexed for MEDLINE]
J Psychiatry Neurosci. 2004 Jul;29(4):268-79.
Transcranial magnetic stimulation (TMS) of the human frontal cortex:
implications for repetitive TMS treatment of depression.
Paus T, Barrett J.
Neuropsychology Department, Montreal Neurological Institute, McGill University,
Montreal, Que. tomas@bic.mni.mcgill.ca
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool used
to manipulate activity in specific neural circuits of the human brain. Clinical
studies suggest that, in some patients with major depression, rTMS has the
potential to alleviate symptoms that may be related to functional abnormalities
in a frontocingulate circuit. This paper reviews the rationale for the use of
rTMS in this context. The following topics are discussed: symptoms and cognition
in major depression, with special emphasis on the initiation of speech;
neuroimaging studies of depression; rTMS as treatment for depression; structure
and function of the mid-dorsolateral frontal and anterior cingulate cortices;
and combined TMS/positron emission tomography studies of frontocortical
connectivity.
Publication Types:
Review
PMID: 15309043 [PubMed - indexed for MEDLINE]
J Clin Psychiatry. 2004 Jun;65(6):772-82.
No deterioration of cognitive performance in an aggressive unilateral and
bilateral antidepressant rTMS add-on trial.
Hausmann A, Pascual-Leone A, Kemmler G, Rupp CI, Lechner-Schoner T,
Kramer-Reinstadler K, Walpoth M, Mechtcheriakov S, Conca A, Weiss EM.
Department of General Psychiatry, University Hospital Innsbruck, Austria.
armand.hausmann@uibk.ac.at
BACKGROUND: Cognitive functions were assessed before and following a course of
repetitive transcranial magnetic stimulation (rTMS) in patients with depression
participating in a sham-controlled, randomized trial of rTMS as adjunct to
antidepressant treatment. METHOD: Forty-one medicated inpatients with a DSM-IV
diagnosis of a depressive episode were consecutively randomly assigned to 1 of 3
groups comparing 2 active rTMS conditions with sham stimulation. The rTMS was
applied either at high frequency over the left dorsolateral-prefrontal cortex
(DLPFC) (10 sessions x 10 trains x 10 seconds 20 Hz at 100% motor threshold
[MT], 90-second intertrain interval) or in a combined high- and low-frequency
manner to the left and right DLPFC, respectively (10 sessions x 1 train x 10
minutes at 120% MT). Thirty-eight patients completed a neuropsychological test
battery at baseline and following day 14. The cognitive assessment focused on
motor skills, attention, executive functions, learning, and memory. Data were
collected from November 1999 to August 2002. RESULTS: Active treatment groups
did not differ with respect to assessed cognitive measures and thus were pooled.
A comparison of short-term changes (baseline-day 14) in neuropsychological
performance revealed a more favorable time course of the actively treated
patients for encoding in the verbal memory test compared with the
sham-stimulated patients. CONCLUSIONS: Unilateral rTMS as well as bilateral
combined rTMS revealed no detrimental effects on cognition, as compared with the
sham group. Moreover, neither the add-on design nor the used aggressive
parameters had a negative impact on cognitive measures in comparison with sham.
Repetitive transcranial magnetic stimulation might have mild beneficial
cognitive effects partly independent of its antidepressant efficacy.
Publication Types:
Clinical Trial
Randomized Controlled Trial
Review
Review of Reported Cases
PMID: 15291654 [PubMed - indexed for MEDLINE]
Depress Anxiety. 2004;19(4):249-56.
Safety and benefits of distance-adjusted prefrontal transcranial magnetic
stimulation in depressed patients 55-75 years of age: a pilot study.
Nahas Z, Li X, Kozel FA, Mirzki D, Memon M, Miller K, Yamanaka K, Anderson B,
Chae JH, Bohning DE, Mintzer J, George MS.
Brain Stimulation Laboratory, Institute of Psychiatry, Medical University of
South Carolina, Charleston, SC 29425, USA. nahasz@musc.edu
In contrast to the effects seen in younger adults, depressed elderly subjects
have shown more modest antidepressant responses to transcranial magnetic
stimulation (TMS). We theorized that higher stimulation intensities in older
depressed subjects with prefrontal atrophy might be needed to stimulate
underlying cortex. In an open design with patients on stable baseline
medications, we treated 18 treatment-resistant elderly depressed subjects (mean
age 61.2 +/- 7.3) with 15 rTMS sessions over 3 weeks. We adjusted the delivered
TMS intensity to account for MRI measured prefrontal atrophy. The skull to
prefrontal cortex distance increased with age, whereas the skull to motor cortex
distance did not. All subjects tolerated the higher doses well. The average
intensity used was 114% of motor threshold (MT) with a range from 103-141% MT.
There was an average 35% decline over the 3 weeks in HRSD scores. After 3 weeks
of treatment, 27% (5/18) met response criteria (> 50% improvement), with four of
these five also meeting criteria for remission (exit Hamilton Depression Score <
8). These initial pilot findings support the need for blinded studies using
prefrontal TMS in an elderly population, testing whether TMS, delivered at
stimulation intensities calculated to overcome atrophy, is more effective than
TMS without adjusting for atrophy.
Publication Types:
Clinical Trial
PMID: 15274174 [PubMed - indexed for MEDLINE]
Biol Psychiatry. 2004 Aug 1;56(3):146-50.
Neurogenesis and depression: etiology or epiphenomenon?
Henn FA, Vollmayr B.
Central Institute of Mental Health, Mannheim, Germany.
The concept that decreased neurogenesis might be the cause of depression is
supported by the effects of stress on neurogenesis and the demonstration that
neurogenesis seems to be necessary for antidepressant action. Data from the
animal models tested to date show that decreasing the rate of neurogenesis does
not lead to depressive behavior. Furthermore, evidence shows that an effective
treatment for depression, transcranial magnetic stimulation, does not alter
rates of neurogenesis. On the basis of these findings, it is suggested that
neurogenesis might play a subtle role in depression but that it is not the
primary factor in the final common pathway leading to depression.
Publication Types:
Review
Review, Tutorial
PMID: 15271582 [PubMed - indexed for MEDLINE]
J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1171-4.
Repetitive transcranial magnetic stimulation is as effective as fluoxetine in
the treatment of depression in patients with Parkinson's disease.
Fregni F, Santos CM, Myczkowski ML, Rigolino R, Gallucci-Neto J, Barbosa ER,
Valente KD, Pascual-Leone A, Marcolin MA.
Department of Neurology, Beth Israel Deaconess Medical Center and Harvard
Medical School, Boston, Massachusetts 02215, USA. ffregni@bidmc.harvard.edu
OBJECTIVE: To study the efficacy of 15 Hz repetitive transcranial magnetic
stimulation (rTMS) in treating depression in patients with Parkinson's disease.
METHODS: 42 patients were enrolled into two groups: group 1, active rTMS (15 Hz
rTMS for 10 days) and placebo drug treatment; group 2, sham rTMS and fluoxetine
20 mg/day. A specially designed sham coil was used for sham stimulation. The
unified Parkinson's disease rating scale (UPDRS), activities of daily living
(ADL), Hamilton rating scale for depression (HRSD), Beck depression inventory
(BDI), and mini-mental state examination (MMSE) were assessed by a rater blinded
to treatment arm. RESULTS: HRSD and BDI were improved to the same extent in both
groups after two weeks of treatment (38% and 32% for group 1, 41% and 33% for
group 2, respectively). At week 8 there was a tendency for worse motor UPDRS
scores in group 2 (NS). ADL showed improvement at week 8 only in group 1. MMSE
improved in both groups after treatment, but faster in group 1 than in group 2.
There were fewer adverse effects in group 1 than in group 2. CONCLUSIONS: rTMS
has the same antidepressant efficacy as fluoxetine and may have the additional
advantage of some motor improvement and earlier cognitive improvement, with
fewer adverse effects.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15258224 [PubMed - indexed for MEDLINE]
CNS Spectr. 2004 Jun;9(6):476-82.
Decision analysis of the cost-effectiveness of repetitive transcranial magnetic
stimulation versus electroconvulsive therapy for treatment of nonpsychotic
severe depression.
Kozel FA, George MS, Simpson KN.
Brain Stimulation Laboratory, Department of Psychiatry, Medical University of
South Carolina, and Ralph H. Johnson Veterans Affairs Medical Center,
Charleston, USA. kozelfa@musc.edu
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a new
treatment with promise for resistant depression. OBJECTIVE: We tested the
economic feasibility of this new method compared with electroconvulsive therapy
(ECT). METHOD: An economic decision analysis was used to compare the costs of
three different treatment strategies for nonpsychotic severe depression. The
strategies were: ECT alone; rTMS alone; and rTMS followed by ECT for
nonresponders (rTMS-to-ECT). We calculated 12-month costs and quality adjusted
life years (QALYs) for the three treatment options for all nonpsychotic,
severely depressed United States patients who would have otherwise undergone
ECT. A sensitivity analysis was performed to test the degree of change in
outcome with various parameter changes. RESULTS: The additional cost of using
ECT alone compared with rTMS alone was 460,031 US dollars per quality adjusted
year of life gained. For ECT versus rTMS-to-ECT, there was both an increased
cost and a loss of 1,538 QALYs with ECT alone. The sensitivity analysis revealed
the model to be robust with various parameter changes. CONCLUSION: If rTMS were
to be made widely available clinically in the US, it would offer a substantial
economic benefit over ECT in treating resistant depression. Using rTMS-to-ECT
offers not only an economic advantage but also an increase in QALYs. This
analysis suggests that rTMS would be a cost-effective treatment for depression
compared with the current option of ECT alone.
PMID: 15162090 [PubMed - indexed for MEDLINE]
Psychiatry Res. 2004 Apr 30;126(2):123-33.
Repetitive transcranial magnetic stimulation: a putative add-on treatment for
major depression in elderly patients.
Mosimann UP, Schmitt W, Greenberg BD, Kosel M, Muri RM, Berkhoff M, Hess CW,
Fisch HU, Schlaepfer TE.
Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne
NE4 6BE, UK.
Repetitive transcranial magnetic stimulation (rTMS) is a recent putative
treatment for affective disorders. Several studies have demonstrated
antidepressant effects of rTMS in younger patients; we aimed to assess its
effect in older outpatients with treatment-resistant major depression.
Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were
randomized for sham or real stimulation and received 10 daily rTMS sessions (20
Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition
to the antidepressant medication. For sham stimulation, the coil was tilted 90
degrees. Depression severity was assessed using the Hamilton Depression Rating
Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom
scale, and a visual analog depression scale. Mini-Mental Status Examination
performance, memory, and executive and attentional functions were measured to
control for cognitive side effects. Depression ratings revealed significant
antidepressant effects within 2 weeks in both sham and real stimulation groups;
however, there were no between-group differences. Treatment with rTMS was safe;
adverse events were rare and not more prevalent in either group, and cognitive
assessment did not show any deterioration. We were unable to demonstrate any
additional antidepressant effects of real stimulation in elderly patients with
treatment-resistant major depression. Therapeutic effects of rTMS in this
clinically challenging patient group remain to be demonstrated.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15123391 [PubMed - indexed for MEDLINE]
Clin EEG Neurosci. 2004 Jan;35(1):4-13.
Current status of the utilization of antiepileptic treatments in mood, anxiety
and aggression: drugs and devices.
Barry JJ, Lembke A, Bullock KD.
Department of Psychiatry, Stanford University Medical Center, 401 Quarry Road MC
5723, Stanford, CA 94305, USA. jbarry@leland.stanford.edu
Interventions that have been utilized to control seizures in people with
epilepsy have been employed by the psychiatric community to treat a variety of
disorders. The purpose of this review will be to give an overview of the most
prominent uses of antiepileptic drugs (AEDs) and devices like the Vagus Nerve
Stimulator (VNS) and Transcranial Magnetic Stimulation (TMS) in the treatment of
psychiatric disease states. By far, the most prevalent use of these
interventions is in the treatment of mood disorders. AEDs have become a mainstay
in the effective treatment of Bipolar Affective Disorder (BAD). The U.S. Food
and Drug Administration has approved the use of valproic acid for acute mania,
and lamotrigine for BAD maintenance therapy. AEDs are also effectively employed
in the treatment of anxiety and aggressive disorders. Finally, VNS and TMS are
emerging as possibly useful tools in the treatment of more refractory depressive
illness.
Publication Types:
Review
PMID: 15112459 [PubMed - indexed for MEDLINE]
Eur Psychiatry. 2004 Apr;19(2):118-9.
ECT response after relapse during continuation repetitive transcranial magnetic
stimulation. A case report.
Conca A, Hrubos W, Di Pauli J, Konig P, Hausmann A.
Department of Psychiatry I, Regional Hospital of Rankweil, LKH Rankweil,
Valunastr. 16, Rankweil 6830, Austria. andreas.conca@lkhr.at
Research on repetitive transcranial magnetic stimulation (rTMS) indicates that
the treatment of non-psychotic depression is comparable to electroconvulsive
therapy (ECT) in terms of short-term outcome. We report on a woman who exerted a
recurrent moderate major depressive episode, 6 months after discontinuation of
maintenance ECT. She responded to acute rTMS treatment which was followed by the
rTMS maintenance-protocol. Within 2 months of continuation rTMS she relapsed
suffering from a severe non psychotic depressive episode and had to be switched
to a successful ECT. In this patient rTMS had a good clinical impact as an acute
treatment strategy, but failed to prevent relapse as the continuation ECT
previously did in the same patient.
Publication Types:
Case Reports
PMID: 15051113 [PubMed - indexed for MEDLINE]
Neurosci Lett. 2004 Apr 1;358(3):193-6.
Slow repetitive transcranial magnetic stimulation increases somatosensory
high-frequency oscillations in humans.
Ogawa A, Ukai S, Shinosaki K, Yamamoto M, Kawaguchi S, Ishii R, Takeda M.
Department of Psychiatry and Behavioral Science, Osaka University Graduate
School of Medicine, Suita, Osaka 565-0871, Japan. ogawa@psy.med.osaka-u.ac.jjp
Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a
possible treatment for psychiatric and neurological disorders characterized by
focal brain excitability, such as major depression and action myoclonus.
However, the mechanism of modulating excitability by rTMS is unclear. We
examined the changes in high frequency oscillations (HFOs) of somatosensory
evoked potentials (SEPs) before and after slow rTMS over the right primary
somatosensory cortex (0.5 Hz, 50 pulses, 80% motor threshold intensity). The
HFOs, which represent a localized activity of intracortical inhibitory
interneurons, were significantly increased after slow rTMS, while the SEPs were
not changed. Our results suggest that slow rTMS affects cortical excitability by
modulating the activity of the intracortical inhibitory interneurons beyond the
time of the stimulation and that rTMS may have therapeutic effects on such
disorders.
PMID: 15039114 [PubMed - indexed for MEDLINE]
Ned Tijdschr Geneeskd. 2004 Feb 28;148(9):410-5.
Comment in:
Ned Tijdschr Geneeskd. 2004 Feb 28;148(9):408-10.
[Repetitive transcranial magnetic stimulation in depression; stimulation of the
brain in order to cure the psyche]
[Article in Dutch]
Helmich RC, Snijders AH, Verkes RJ, Bloem BR.
Universitair Medisch Centrum St Radboud, Postbus 9101, 6500 HB Nijmegen.
Transcranial magnetic stimulation (TMS) is a non-invasive approach to briefly
stimulate or inhibit cortical brain areas. A novel approach entails the delivery
of repetitive TMS pulses (rTMS) at a fixed frequency. In rTMS cortical activity
is altered beyond the period of actual stimulation. The changes occur locally as
well as at a distance in functionally connected brain areas. These features
render rTMS a suitable tool to study normal brain functions and the
pathophysiology of brain diseases. Furthermore, it is expected that rTMS could
be used as a novel therapy for neurological or psychiatric diseases
characterised by abnormal cortical activation. This possibility has been studied
mostly in patients suffering from depression, where rTMS has been used to
restore normal activity in the hypoactive prefrontal cortex. Despite
statistically significant therapeutic effects in small sized trials, the
clinical implications are still limited.
Publication Types:
Review
Review, Tutorial
PMID: 15038199 [PubMed - indexed for MEDLINE]
Ned Tijdschr Geneeskd. 2004 Feb 28;148(9):408-10.
Comment on:
Ned Tijdschr Geneeskd. 2004 Feb 28;148(9):410-5.
[Transcranial magnetic stimulation: a fascinating development]
[Article in Dutch]
Koerselman GF.
Universitair Medisch Centrum Utrecht, afd. Psychiatrie, Heidelberglaan 100, 3584
GA Utrecht.
Transcranial magnetic stimulation is a novel technique for safely stimulating or
inhibiting cortical brain functions. Its possible role in neurology and
psychiatry is the subject of a broad field of research. At present, standard
clinical implementation is not yet warranted. On the other hand, the technique
as such is quite promising, especially because it can pave the way to a
'bottom-up' approach to mental disorder, starting from basic psychobiological
concepts and then gradually developing in the direction of more complex clinical
applications.
Publication Types:
Comment
PMID: 15038198 [PubMed - indexed for MEDLINE]
Depress Anxiety. 2004;19(1):59-62.
Slow right prefrontal transcranial magnetic stimulation as a treatment for
medication-resistant depression: a double-blind, placebo-controlled study.
Kauffmann CD, Cheema MA, Miller BE.
Over the past decade, efforts have been made to assess the positive therapeutic
effects of transcranial magnetic stimulation (TMS) by altering the excitability
of the brain. We conducted a double-blind, placebo-controlled study to assess
the efficacy of right prefrontal slow repetitive TMS in patients with treatment
refractory major depression. This pilot study supports the therapeutic potential
of rTMS in the low-frequency range of 1 Hz on right prefrontal cortex for the
treatment of refractory major depression. Additional studies will be necessary
to assess the efficacy of rTMS with different indices (frequency, intensity, and
stimulation site) for major depression and other psychiatric diseases. Copyright
2004 Wiley-Liss, Inc.
Publication Types:
Clinical Trial
Letter
Randomized Controlled Trial
PMID: 14978787 [PubMed - indexed for MEDLINE]
Depress Anxiety. 2004;19(1):24-30.
Shorter duration of depressive episode may predict response to repetitive
transcranial magnetic stimulation.
Holtzheimer PE 3rd, Russo J, Claypoole KH, Roy-Byrne P, Avery DH.
Department of Psychiatry and Behavioral Sciences, University of Washington
Medical Center, Harborview Medical Center, Seattle, Washington 98104, USA.
photzmr@u.washington.edu
We investigated repetitive transcranial magnetic stimulation (rTMS) as a
treatment for major depression. The experimental design comprised 15
medication-free subjects with major depressive disorder who were randomly
assigned to receive 10 sessions of active or sham 10-Hz rTMS to the left
dorsolateral prefrontal cortex at 110% motor threshold. Depression severity was
measured by the Hamilton Depression Rating Scale (HDRS) and Beck Depression
Inventory (BDI). Nonresponders to sham were allowed to receive active rTMS with
the same parameters. Response to treatment was analyzed using a random
regression model including episode duration and number of prior antidepressant
treatments as covariates. Treatment (rTMS vs. sham) did not significantly
predict changes in depression severity. Shorter duration of episode and more
lifetime treatment trials significantly predicted improvements in BDI but not
HDRS scores. Data from all subjects who received active rTMS (n = 14) showed
that those with a depressive episode duration of shorter than 4 years had a mean
HDRS decrease of 52% compared to 6% in those with an episode duration longer
than 10 years. Active rTMS was well tolerated and was not associated with
neuropsychological decrements when compared to sham. No significant
antidepressant effects were found for 2 weeks of rTMS compared to sham. Among
all subjects receiving rTMS those with a shorter duration of the current episode
showed a greater response. Patients may need more than 10 treatments to obtain
full benefit from rTMS. The design of future rTMS studies should consider these
issues. Copyright 2004 Wiley-Liss, Inc.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14978782 [PubMed - indexed for MEDLINE]
Biol Psychiatry. 2004 Feb 15;55(4):398-405.
Repetitive transcranial magnetic stimulation as treatment of poststroke
depression: a preliminary study.
Jorge RE, Robinson RG, Tateno A, Narushima K, Acion L, Moser D, Arndt S,
Chemerinski E.
Department of Psychiatry, Carver College of Medicine, University of Iowa,
Psychiatry Research/2-202 MEB, Iowa City, IA 52242-1000, USA.
BACKGROUND: Depression has a significant impact on poststroke recovery and
mortality. There are a proportion of patients with poststroke depression (PSD)
who do not respond to antidepressants. Repetitive Transcranial Magnetic
Stimulation (rTMS) might be a safe and effective alternative in these refractory
cases. METHODS: We conducted a randomized, parallel, double-blind study of
active versus sham left prefrontal rTMS in patients with refractory PSD. After
discontinuing antidepressants, patients were randomly assigned to receive 10
sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds
duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores,
response and remission rates. Patients completed a neuropsychological battery at
baseline and after completing the protocol. RESULTS: When compared with sham
stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal
cortex were associated with a significant reduction of depressive symptoms. This
reduction was not influenced by patient's age, type or location of stroke,
volume of left frontal leukoaraiosis or by the distance of the stimulating coil
to the prefrontal cortex. However, there was a significant positive correlation
between the percentage of reduction of Ham-D scores and frontal gray and white
matter volumes. There were no significant changes in cognitive functioning
between the active and the sham stimulation groups. In addition, there were few
and mild adverse effects that were equally distributed among groups.
CONCLUSIONS: Taken together, these preliminary findings suggest that rTMS may be
an effective and safe treatment alternative for patients with refractory
depression and stroke.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14960293 [PubMed - indexed for MEDLINE]
J Neurol Neurosurg Psychiatry. 2004 Feb;75(2):320-2.
No benefit derived from repetitive transcranial magnetic stimulation in
depression: a prospective, single centre, randomised, double blind, sham
controlled "add on" trial.
Hausmann A, Kemmler G, Walpoth M, Mechtcheriakov S, Kramer-Reinstadler K,
Lechner T, Walch T, Deisenhammer EA, Kofler M, Rupp CI, Hinterhuber H, Conca A.
University Hospital Innsbruck, Department of General Psychiatry, Innsbruck,
Austria. armand.hausmann@uibk.ac.at
Repetitive transcranial magnetic stimulation (rTMS) has been reported to
demonstrate slight effects in the treatment of depression. Hence, a novel
bilateral versus unilateral and sham stimulation design was applied to further
assess rTMS' antidepressant effects. Forty one medication free patients with
major depression, admitted to a psychiatric unit specialising in affective
disorders, were consecutively randomised into 3 groups. Group A1 (n = 12)
received unilateral active stimulation consisting of high frequency (hf) rTMS
over the left dorsolateral prefrontal cortex (LDLPC) and subsequent sham low
frequency (lf) rTMS over the right dorsolateral prefrontal cortex (RDLPC). Group
A2 (n = 13) received simultaneous bilateral active stimulation consisting of
hf-rTMS over the LDLPC and lf-rTMS over the RDLPC. Group C (n = 13) received
bilateral sham stimulation. Stimulation was performed on 10 consecutive
workdays. All patients received antidepressant medication on the first day of
stimulation, which was continued during and after the stimulation period. As no
significant difference in antidepressant outcome between group A1 and A2 was
found, the two groups were pooled. The time course of the outcome variables
Hamilton depression rating scale (HDRS(21)) and Beck depression inventory (days
0, 7, 14, 28) by repeated measures analysis of variance revealed no significant
group differences (in terms of a group by time interaction), whereas there was a
significant effect of time on all three outcome variables in all groups. The
results suggest that rTMS as an "add on" strategy, applied in a unilateral and a
bilateral stimulation paradigm, does not exert an additional antidepressant
effect.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14742619 [PubMed - indexed for MEDLINE]
Int J Ment Health Nurs. 2003 Mar;12(1):22-9.
Information for assistants of repeated transcranial magnetic stimulation.
Pridmore S, Khan U, Rosa MA, George MS.
Department of Psychological Medicine, Royal Hobart Hospital, Discipline of
Psychiatry, University of Tasmania, GPO Box 1061 L, Hobart 7001, Tasmania,
Australia. s.pridmore@utas.edu.au
Repeated transcranial magnetic stimulation (rTMS) is an exciting new technology
being used in psychiatric and neurological research in many centres around the
world. rTMS has been accepted as a routine treatment of depression in Canada and
Israel. To this point, it has been exclusively conducted by medical officers. As
knowledge and experience grows, it is probable that professionals with other
backgrounds will have the opportunity to play a role. The aim of this paper is
to provide information that will be valuable to assistants. Electromagnetic
principles are harnessed to deliver electric currents to localized regions of
the cortex. rTMS does not involve anaesthesia or seizure. Side-effects appear to
be few. Much remains uncertain, however, even including the most appropriate
treatment parameters.
Publication Types:
Review
Review, Tutorial
PMID: 14685956 [PubMed - indexed for MEDLINE]
Int J Neuropsychopharmacol. 2003 Dec;6(4):371-8.
Motor-evoked potential amplitudes elicited by transcranial magnetic stimulation
do not differentiate between patients and normal controls.
Grunhaus L, Polak D, Amiaz R, Dannon PN.
Psychiatry Division, Sheba Medical Centre, Tel Hashomer, Israel.
grunhaus@sheba.gov.il
Transcranial magnetic stimulation (TMS) applied over the motor cortex
depolarizes neurons and leads to motor-evoked potentials (MEP). To assess
cortico-spinal excitability we compared the motor threshold (MT) and the
averaged MEP amplitude generated by TMS in patients with major depression (MD)
and matched controls. Nineteen patients, who where participants in a protocol
comparing the antidepressant effects of rTMS with those of ECT, and thirteen
age- and gender-matched normal controls were studied. MT was similar between
patients and normal controls. The MEP amplitude response was significantly
increased by rTMS, however, the magnitude of the response was similar in
patients and normal controls. Correlations between the averaged MEP amplitude
and age revealed that older subjects demonstrated significantly lower responses
at all time-points. We conclude that cortico-spinal excitability is increased
following rTMS, however, differences between patients and normal controls were
not apparent with the paradigm used.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14604452 [PubMed - indexed for MEDLINE]
Arch Gen Psychiatry. 2003 Oct;60(10):1002-8.
Transcranial magnetic stimulation in the treatment of depression: a
double-blind, placebo-controlled trial.
Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, De Castella A, Kulkarni J.
Alfred Psychiatry Research Centre, The Alfred Hospital, and the Department of
Psychological Medicine, Monash University, Australia.
paul.fitzgerald@med.monash.edu.au
BACKGROUND: High-frequency left-sided repetitive transcranial magnetic
stimulation (HFL-TMS) has been shown to have antidepressant effects in
double-blind trials. Low-frequency stimulation to the right prefrontal cortex
(LFR-TMS) has also shown promise, although it has not been assessed in
treatment-resistant depression and its effects have not been compared with those
of HFL-TMS. OBJECTIVE: To prospectively evaluate the efficacy of HFL-TMS and
LFR-TMS in treatment-resistant depression and compared with a sham-treated
control group. DESIGN: A double-blind, randomized, sham-controlled trial.
SETTING: Two general psychiatric services. PARTICIPANTS: Sixty patients with
treatment-resistant depression who had failed to respond to therapy with
multiple antidepressant medications were divided into 3 groups of 20 that did
not differ in age, sex, or any clinical variables. All patients completed the
double-blind phase of the study. INTERVENTIONS: Twenty 5-second HFL-TMS trains
at 10 Hz and five 60-second LFR-TMS trains at 1 Hz were applied daily. Sham
stimulation was applied with the coil angled at 45 degrees from the scalp,
resting on the side of one wing of the coil.Main Outcome Measure Score on the
Montgomery-Asberg Depression Rating Scale. RESULTS: There was a significant
difference in response among the 3 groups (F56,2 = 6.2), with a significant
difference between the HFL-TMS and sham groups and between the LFR-TMS and sham
groups (P<.005 for all) but not between the 2 treatment groups. Baseline
psychomotor agitation predicted successful response to treatment. CONCLUSIONS:
Both HFL-TMS and LFR-TMS have treatment efficacy in patients with
medication-resistant major depression. Treatment for at least 4 weeks is
necessary for clinically meaningful benefits to be achieved. Treatment with
LFR-TMS may prove to be an appropriate initial repetitive TMS strategy in
depression taking into account safety, tolerability, and efficacy
considerations.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14557145 [PubMed - indexed for MEDLINE]
Psychiatry Res. 2003 Aug 30;120(1):95-101.
Reductions in phenomenological, physiological and attentional indices of
depressive mood after 2 Hz rTMS over the right parietal cortex in healthy human
subjects.
van Honk J, Schutter DJ, Putman P, de Haan EH, d'Alfonso AA.
Helmholtz Research Institute, Utrecht University, Heidelberglaan 2, 3584 CS,
Utrecht, The Netherlands. J.vanHonk@fss.uu.nl
Research into emotion and emotional disorders by repetitive transcranial
magnetic stimulation (rTMS) has largely been restricted to the prefrontal
regions. There is, however, also evidence for the parietal cortex being
implicated in emotional (dys-)functioning. Here we used rTMS to investigate a
role of the right parietal cortex in depression. In a placebo-controlled design,
2 Hz rTMS at 90% of the individual motor threshold (MT) was applied over the
right parietal cortex of eight healthy subjects for 20 min continuously. Effects
on mood, autonomic activity and motivated attention were investigated.
Significant reductions in depressive mood were observed immediately following
and 30 min after stimulation. Moreover, these findings were objectified by a
concurring pattern of autonomically mediated changes in the attentional
processing of angry facial expressions. These data suggest a role for the right
parietal cortex in affective brain circuits regulating phenomenological,
physiological and attentional aspects of depressive functioning.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 14500118 [PubMed - indexed for MEDLINE]
Fortschr Neurol Psychiatr. 2003 Sep;71(9):449-57.
[Interhemispheric transfer and its implications for neurology and psychiatry]
[Article in German]
von Richthofen S, Tabrizian S, Grabe HJ, Meyer BU.
Klinik fur Psychiatrie und Psychotherapie des Universitatsklinikums Eppendorf,
Hamburg.
The corpus callosum (