Acta Neuropsychiatr. 2015 Apr;27(2):119-25. doi: 10.1017/neu.2014.44. Epub 2015 Jan 13.
A 2-year follow-up study
of patients participating in our transcranial pulsating electromagnetic
fields augmentation in treatment-resistant depression.
Bech P1, Lindberg L1, Straasø B1, Larsen ER2.
Author information
11Psychiatric Research Unit,Psychiatric Centre North Zealand,Copenhagen University Hospital,Hillerød,Denmark.
22Department of Affective Disorders,Mood Disorders Research Unit,Aarhus University Hospital,Denmark.
Abstract
OBJECTIVE:
We have made a 2-year follow-up study to evaluate the effect of repeated
transcranial pulsating electromagnetic fields (T-PEMF) augmentation in
patients who had achieved remission but later on relapsed, as well as to
identify factors contributing to treatment-resistant depression in
patients who did not respond to T-PEMF.
METHODS:
Using the Longitudinal Expert Assessment of All Data approach the
patients were classified in four groups: A: patients who achieved
remission; B: patients with doubtful effect; C: patients with no effect;
and D: patients who were hard-to-assess.
RESULTS:
In group A, comprising 27 patients, 13 had relapsed; they obtained a
clear remission after a repeated course of T-PEMF augmentation. In group
D, comprising 16 patients, we identified misdiagnostic factors both
concerning the event of remission after the previous T-PEMF augmentation
and concerning the aetiology (psychosocial stressors and co-morbid
conditions). Compared with the other groups, the group D patients had a
smaller number of previous episodes (p=0.09) and a longer duration of
the current episode (p=0.01).
CONCLUSION:
T-PEMF has an effect among patients who relapsed after remission with
the first series of T-PEMF. Treatment-resistant depression is a
condition that has a high degree of multivariate problems. Misuse of
alcohol or drugs, severe somatic disorders and other psychosocial
problems may need other kinds of treatment before T-PEMF augmentation.
Acta Neuropsychiatr. 2014 Oct 2:1-7. [Epub ahead of print]
The Diagnostic Apathia Scale predicts a dose-remission relationship of T-PEMF in treatment-resistant depression.
Bech P1, Lunde M1, Lauritzen L1, Straasø B1, Lindberg L1, Vinberg M2, Undén M1, Hellström LC3, Dissing S4, Larsen ER5.
- 11Psychiatric Research Unit,Psychiatric Centre North Zealand,Copenhagen University Hospital,Hillerød,Denmark.
- 22Department of Psychiatry,Psychiatric Centre Copenhagen,Copenhagen University Hospital,Copenhagen,Denmark.
- 33Psychiatric Research Unit,Psychiatric Centre Copenhagen,Copenhagen University Hospital,Copenhagen NV,Denmark.
- 44Department of Cellular and Molecular Medicine,Panum institute,University of Copenhagen,Copenhagen,Denmark.
- 55Department of Affective Disorders,Mood Disorders Research Unit,Aarhus University Hospital,Aarhus,Denmark.
Abstract
OBJECTIVE:
The aim of this study was to evaluate
the predictive validity of the apathy subsyndrome in patients with
therapy-resistant depression in the dose-remission study with
transcranial pulsating electromagnetic fields (T-PEMF).
METHODS:
The apathy subsyndrome consists of the
symptoms of fatigue, concentration and memory problems, lack of
interests, difficulties in making decisions, and sleep problems. We
evaluated 65 patients with therapy-resistant depression. In total, 34 of
these patients received placebo T-PEMF in the afternoon and active
T-PEMF in the morning, that is, one daily dose. The remaining 31
patients received active T-PEMF twice daily. Duration of treatment was 8
weeks in both groups. The Hamilton Depression Scale (HAM-D17) and the
Bech-Rafaelsen Melancholia Scale (MES) were used to measure remission.
We also focused on the Diagnostic Apathia Scale, which is based on a
mixture of items from the MINI and the HAM-D17/MES.
RESULTS:
In patients without apathy, the
remission rate after T-PEMF was 83.9% versus 58.8% in patients with
apathy (p?0.05). In patients without apathy receiving one active dose
daily 94.4% remitted versus 50% for patients with apathy (p?0.05). In
patients without apathy who received two active doses 69.9% remitted
versus 66.7% for patients with apathy (p?0.05).
CONCLUSION:
Taking the baseline diagnosis of the
apathy syndrome into consideration, we found that in patients without
apathy one daily dose of T-PEMF is sufficient, but in patients with
apathy two daily doses are necessary. Including the apathy syndrome as
predictor in future studies would seem to be clinically relevant.
Acta Neuropsychiatr. 2014 Oct;26(5):272-9. doi: 10.1017/neu.2014.5.
Dose-remission
of pulsating electromagnetic fields as augmentation in
therapy-resistant depression: a randomized, double-blind controlled
study.
Straasø B1, Lauritzen L1, Lunde M1, Vinberg M2, Lindberg L1, Larsen ER3, Dissing S4, Bech P1.
- 11Psychiatric Research Unit,Psychiatric Centre North Zealand,Copenhagen University Hospital,Hillerød,Denmark.
- 22Department of Psychiatry,Psychiatric Centre Copenhagen,Copenhagen University Hospital,Denmark.
- 33Department of Affective Disorders,Mood Disorders Research Unit,Aarhus University Hospital,Denmark.
- 44Department of Cellular and Molecular Medicine,Panum Institute,University of Copenhagen,Copenhagen,Denmark.
Abstract
OBJECTIVE:
To evaluate to what extent a twice
daily dose of Transcranial Pulsating ElectroMagnetic Fields (T-PEMF) was
superior to once daily in patients with treatment-resistant depression
as to obtaining symptom remission after 8 weeks of augmentation therapy.
METHODS:
A self-treatment set-up of the T-PEMF
device was used allowing self-administration by patients in own homes.
All patients were treated for 30 min per T-PEMF session. The
antidepressant medication the patients were receiving at baseline
remained unchanged during the trial. The patients were randomised to
either one T-PEMF dose (active dose in the morning and sham in the
afternoon) or two T-PEMF doses (active dose both morning and afternoon)
in a double-blind procedure. A score of 7 or less on the Hamilton
Depression Scale (HAM-D17) was the criterion of remission.
RESULTS:
In total 34 patients received active
T-PEMF once a day and 31 patients twice daily. After 5 weeks of therapy
remission was obtained in 26.5% and 32.3% on one dose and two doses of
T-PEMF, respectively. After 8 weeks the rate of remission was 73.5% and
67.7%, respectively. The side effects as measured by the Udvalget for
Kliniske Undersøgelser scale showed a better toleration of the
antidepresssive medication in both treatment groups, which was reflected
by the WHO-5 well-being scale with increased scores in both groups of
patients.
CONCLUSION:
The high remission rate obtained by
the T-PEMF augmentation was not a dose effect (one versus two daily
T-PEMF sessions) but was explained by the extension of the treatment
period from 5 to 8 weeks.
Int Rev Psychiatry. 2011 Oct;23(5):400-12. doi: 10.3109/09540261.2011.614223.
The use of ECT and MST in treating depression.
Allan CL, Ebmeier KP.
Source
Department of Psychiatry, University of Oxford, Oxford, UK.
Abstract
Electroconvulsive therapy (ECT) has been used clinically since 1938.
Its most common use is in the treatment of depression: first line
treatment where rapid recovery is a priority, but more frequently as an
effective treatment for patients who do not respond to pharmacological
and psychological approaches. Whilst it is widely hailed as an effective
treatment, concerns about its effect on cognition remain. The
development of magnetic seizure therapy (MST) over the past decade has
attempted to devise a therapy with comparable efficacy to ECT, but
without the associated cognitive side effects. The rationale for this is
that MST uses magnetic fields to induce seizures in the cortex, without
electrical stimulation of brain structures involved with memory. MST
has been used successfully in the treatment of depression, yet there is a
dearth of literature in comparison with ECT. We present a systematic
review of the literature on ECT (from 2009-2011) and MST (from
2001-2011).
Biol Psychiatry. 2010 Jul 15;68(2):163-9. Epub 2010 Apr 10.
Transcranial low voltage pulsed electromagnetic fields in patients with treatment-resistant depression.
Martiny K, Lunde M, Bech P.
Psychiatric Research Unit, Mental Health Center North Zealand, Hillerød, Denmark. Klaus.Martiny@regionh.dk
Abstract
BACKGROUND: Approximately 30% of patients with depression are
resistant to antidepressant drugs. Repetitive transcranial magnetic
stimulation (rTMS) has been found effective in combination with
antidepressants in this patient group. The aim of this study was to
evaluate the antidepressant effect of a new principle using
low-intensity transcranially applied pulsed electromagnetic fields
(T-PEMF) in combination with antidepressants in patients with
treatment-resistant depression.
METHODS: This was a sham-controlled double-blind study comparing 5
weeks of active or sham T-PEMF in patients with treatment-resistant
major depression. The antidepressant treatment, to which patients had
been resistant, was unchanged 4 weeks before and during the study
period. Weekly assessments were performed using both clinician-rated and
patient-rated scales. The T-PEMF equipment was designed as a helmet
containing seven separate coils located over the skull that generated an
electrical field in tissue with orders of magnitude weaker than those
generated by rTMS equipment.
RESULTS: Patients on active T-PEMF showed a clinically and
statistically significant better outcome than patients treated with sham
T-PEMF, with an onset of action within the first weeks of therapy.
Effect size on the Hamilton 17-item Depression Rating Scale was .62 (95%
confidence interval .21-1.02). Treatment-emergent side effects were few
and mild.
CONCLUSION: The T-PEMF treatment was superior to sham treatment in
patients with treatment-resistant depression. Few side effects were
observed. Mechanism of the antidepressant action, in light of the known
effects of PEMF stimulation to the brain, is discussed.
Encephale. 2009 Dec;35 Suppl 7:S325-9.
[Electrostimulation techniques in treatment for severe depression]
[Article in French]
Millet B.
Université Rennes 1, Chu de Rennes, Hôpital Guillaume
Régnier, 108 Avenue du Général Leclerc, 35000 Rennes.
bruno.millet@univ-rennes1.fr
Abstract
Electroconvulsivotherapy represents a key indication for severe Major
Depressive Episode (MDE). However, an hospitalization with a general
anaesthesia allowing a seizure induction followed by an almost
systematic post-epileptic delirium justifies the development of other
brain electrostimulation techniques. Trans-cranial Magnetic Stimulation
(TMS) is a technique which offers to transform an electromagnetic field
within the brain in an electric one. This therapeutic has been approved
in 2008 in the MDE indication by the Food and Drug Administration.
However a better knowledge of brain stimulation parameters such as the
number of sequences, intensity, frequency, and the brain target, is
necessary. Indeed it could enable to get some more homogeneous clinical
results which will drive to the use of this technique in daily practice.
Neurosurgical procedures represent also a stake for a better treatment
of severe chronic and resistant depression. Whereas Vagus Nerve
Stimulation (DBS) failed to be developed in France, Deep Brain
Stimulation (DBS) is currently under development in this indication with
some promising preliminary results.
J Affect Disord. 2009 Nov;118(1-3):94-100. Epub 2009 Feb 26.
Low frequency (1-Hz), right prefrontal repetitive transcranial
magnetic stimulation (rTMS) compared with venlafaxine ER in the
treatment of resistant depression: a double-blind, single-centre,
randomized study.
Bares M, Kopecek M, Novak T, Stopkova P, Sos P, Kozeny J, Brunovsky M, Höschl C.
Prague Psychiatric Centre, Ustavni 91, Prague 8 – Bohnice, 181 03, Czech Republic.
Abstract
BACKGROUND: Previous studies have shown effectiveness of repetitive
transcranial magnetic stimulation (rTMS) in the treatment of depression.
This double-blind study compared efficacy of l Hz rTMS over the right
prefrontal dorsolateral cortex with venlafaxine ER in the treatment of
resistant depression. METHODS: A total of 60 inpatients with depressive
disorder (DSM-IV criteria), who previously did not respond to at least
one antidepressant treatment, were randomly assigned to 1 Hz rTMS with
placebo and venlafaxine ER with sham rTMS for 4 weeks. The primary
outcome measure was score change in the Montgomery-Asberg Depression
Rating Scale (MADRS). We also used Clinical Global Impression (CGI) and
Beck Depressive. Inventory-Short Form (BDI-SF). The response was defined
as a >or=50% reduction of MADRS score. RESULTS: There were no
significant differences between treatment groups in MADRS (p=0.38),
BDI-SF (p=0.56) and CGI (p=0.17) scores from baseline to endpoint.
Response rates for rTMS (33%) and venlafaxine (39%) as well as remission
(MADRS score<or=10 points) rates (19% vs. 23%) and drop-out rate did
not differ between treatment groups. There were significant reductions
of MADRS, CGI and BDI-SF scores in both groups. LIMITATIONS: Small
sample size. No placebo arm was included for ethical reasons, because
both treatments have previously been reported to be more effective than
placebo. Relatively short duration of antidepressant treatment.
CONCLUSION: The findings of this study suggest that, at least in the
acute treatment, the right sided rTMS produces clinically relevant
reduction of depressive symptomatology in patients with resistant
depression comparable to venlafaxine ER. Larger sample sizes are
required to confirm these results.
J Clin Psychiatry. 2008 Jun;69(6):930-4.
An open-label, prospective study of repetitive transcranial magnetic
stimulation (rTMS) in the long-term treatment of refractory depression:
reproducibility and duration of the antidepressant effect in
medication-free patients.
Demirtas-Tatlidede A, Mechanic-Hamilton D, Press DZ, Pearlman C, Stern WM, Thall M, Pascual-Leone A.
Berenson-Allen Center for Noninvasive Brain Stimulation, Harvard
Medical School, and the Department of Neurology, Behavioral Neurology
Unit, Beth Israel Deaconess Medical Center, Boston, Mass 02215, USA.
Abstract
OBJECTIVE: Several studies have assessed the acute antidepressant
effects of repetitive transcranial magnetic stimulation (rTMS), and many
have revealed positive results. However, the impact of rTMS throughout
the long course of major depressive disorder (MDD) and the efficacy of
rTMS in the treatment of depressive relapses still remain to be
elucidated.
METHOD: Sixteen medication-free patients with refractory MDD
(diagnosed according to DSM-IV) who initially had clinically significant
antidepressant responses to a 10-day course of 10-Hz rTMS were
consecutively admitted to the protocol from 1997 to 2001 and were
followed for 4 years. The cohort was studied during a total of 64
episodes of depressive relapse. Severity of depression was evaluated
with the Hamilton Rating Scale for Depression (HAM-D) and the Beck
Depression Inventory (BDI) prior to and after completion of each rTMS
treatment course. Clinically significant response was defined as a
reduction in HAM-D score of at least 50%. Safety was assessed by serial
neurologic examinations and neuropsychological evaluations.
RESULTS: Approximately one half of the patients individually
sustained a clinically significant response to the repeated courses of
rTMS; the mean +/- SD decrease in HAM-D scores was 64.8% +/- 12.6% (p
< .0001), and, in BDI scores, 60.4% +/- 20.6% (p < .0001). Despite
the lack of adjuvant antidepressant medication, the mean interval
between treatment courses was approximately 5 months, and the
medication-free period ranged from 26 to 43 months. Transcranial
magnetic stimulation was well tolerated, and evaluations regarding the
safety of the repeated applications of rTMS revealed no findings of
concern.
CONCLUSIONS: Repeated rTMS applications have demonstrated a
reproducible antidepressant effect in patients with refractory
depression who initially showed a clinically significant benefit. The
duration of effect varied across patients, but benefits were sustained
for a mean of nearly 5 months. Further studies with larger cohorts will
be useful in determining the long-term effectiveness of rTMS maintenance
therapy.
Pharmacopsychiatry. 2008 Mar;41(2):41-7.
Repetitive transcranial magnetic stimulation (rTMS) in combination
with escitalopram in patients with treatment-resistant major depression:
a double-blind, randomised, sham-controlled trial.
Bretlau LG, Lunde M, Lindberg L, Undén M, Dissing S, Bech P.
Psychiatric Research Unit, Frederiksborg General Hospital, Hillerød, Denmark.
Abstract
BACKGROUND: The role of high-frequency rTMS over the left cortex as
an add-on strategy in the treatment of major depression is still
uncertain even in patients resistant to pharmacotherapy. We had planned a
large sham TMS controlled study in the acute phase with a
placebo-controlled relapse-prevention phase with escitalopram. However,
because a recent meta-analysis showed only a small effect size of rTMS
over sham TMS in the acute treatment phase of depressed patients, we
decided to make an interim analysis. METHOD: In patients with
medication-resistant major depression we administered in a randomised
trial 15 sessions of sham-controlled rTMS over three weeks in
combination with 20 mg escitalopram daily. After the last rTMS, the
patients were followed for another 9 weeks on 20 mg escitalopram daily.
The antidepressant effect was measured by the HAM-D(6) as primary
outcome scale. RESULTS: A total of 45 patients with complete data were
randomised so that 23 patients received sham TMS and 22 patients
received active, high-frequency rTMS over the left cortex. Over the 3
weeks, the active rTMS treatment was superior to sham TMS with effect
sizes on the HAM-D(6) above 0.70, which indicates not only a
statistically but also a clinically significant effect. The patients had
typically been through two failed antidepressant treatment attempts
with non-tricyclics before inclusion in the study. Both the rTMS and
escitalopram were well-tolerated. CONCLUSION: High-frequency rTMS over
the left cortex is an add-on strategy of clinical significance in
combination with escitalopram in patients with major depression
resistant to non-tricyclic antidepressants. Pharmacopsychiatry. 2008 Mar;41(2):41-7.
Repetitive transcranial magnetic stimulation (rTMS) in combination
with escitalopram in patients with treatment-resistant major depression:
a double-blind, randomised, sham-controlled trial.
Bretlau LG, Lunde M, Lindberg L, Undén M, Dissing S, Bech P.
Psychiatric Research Unit, Frederiksborg General Hospital, Hillerød, Denmark.
Abstract
BACKGROUND: The role of high-frequency rTMS over the left cortex as
an add-on strategy in the treatment of major depression is still
uncertain even in patients resistant to pharmacotherapy. We had planned a
large sham TMS controlled study in the acute phase with a
placebo-controlled relapse-prevention phase with escitalopram. However,
because a recent meta-analysis showed only a small effect size of rTMS
over sham TMS in the acute treatment phase of depressed patients, we
decided to make an interim analysis.
METHOD: In patients with medication-resistant major depression we
administered in a randomised trial 15 sessions of sham-controlled rTMS
over three weeks in combination with 20 mg escitalopram daily. After the
last rTMS, the patients were followed for another 9 weeks on 20 mg
escitalopram daily. The antidepressant effect was measured by the
HAM-D(6) as primary outcome scale.
RESULTS: A total of 45 patients with complete data were randomised so
that 23 patients received sham TMS and 22 patients received active,
high-frequency rTMS over the left cortex. Over the 3 weeks, the active
rTMS treatment was superior to sham TMS with effect sizes on the
HAM-D(6) above 0.70, which indicates not only a statistically but also a
clinically significant effect. The patients had typically been through
two failed antidepressant treatment attempts with non-tricyclics before
inclusion in the study. Both the rTMS and escitalopram were
well-tolerated.
CONCLUSION: High-frequency rTMS over the left cortex is an add-on
strategy of clinical significance in combination with escitalopram in
patients with major depression resistant to non-tricyclic
antidepressants.
Encephale. 2007 Mar-Apr;33(2):126-34.
[Efficacy of repetitive transcranial magnetic stimulation (rTMS) in major depression: a review]
[Article in French]
Brunelin J, Poulet E, Boeuve C, Zeroug-vial H, d’Amato T, Saoud M.
EA 3092, UCBL, Professeur J. Daléry, CH Le Vinatier, 95 boulevard Pinel, 69677 Bron cedex.
Abstract
INTRODUCTION: In 1985, Barker et al. showed that it was possible to
stimulate both nerves and brain using external magnetic stimulation
without significant pain. During the past 10 years, therapeutic effects
of repeated Transcranial Magnetic Stimulation (rTMS) have been widely
studied in psychiatry and its efficacy has been demonstrated in the
treatment of major depressive disorders, particularly as an alternative
to electroconvulsivotherapy (ECT). Facing the large range of studies, we
found necessary to propose an up-to-date review in French of the
methodological and therapeutic variations among them.
METHOD: Based on an exhaustive consultation of Medline data and the
Avery-George-Holtzheimer Database of rTMS Depression-Studies,
supplemented by a manual research, only works evaluating the therapeutic
efficacy of rTMS on depressive symptoms were retained, excluding all
studies exclusively investigating the stimulation parameters or the
tolerance as well as case reports.
RESULTS: Out the 66 available reports we retained 30 studies. After a
description of the main results of these 30 studies, several elements
of the 66 will be discussed. Open studies demonstrated that short
courses rTMS (5 to 10 sessions) produced a decrease in the mean Hamilton
Depression Ratting Scale (HDRS) scores, although significant remission
of depression in individuals was rare. Most authors had used high
frequency rTMS applied to the left Dorso Lateral Prefrontal Cortex (left
DLPFC). However, low frequency rTMS applied to the right DLPFC was also
followed by significant reduction of HDRS scores. Parallel arm, double
blind versus placebo studies are designed to clarify the therapeutic
efficacy of rTMS therapy but conclude in contradicting results.
Literature data globally confirms a greater efficacy of rTMS compared to
placebo (37% responders in the active group vs 20% in the sham). This
efficacy could in fact be even greater because the sham procedure is
disputable in most studies. Indeed, positioning rTMS coil at 45 or 90
from the scalp may not represent an accurate sham procedure and the use
of real sham coil is to be recommended. Only one study has suggested
that associating rTMS and ECT could decrease the number of general
anesthesia required. Therapeutic efficacy has been shown by either
inhibiting the right DLPFC or by stimulating the left DLPFC, although
some patients exhibit paradoxical responses. High frequency rTMS (>5
Hz) increases cortical excitability and metabolism, while low-frequency
rTMS stimulation ( 1 Hz) has the opposite effect. Other parameters are:
relevant: intensity (from 80 to 110% of motor threshold), total number
of stimulations (from 120 to 2 000) and total number of rTMS sessions
(from 5 to 20). As suggested in most recent studies, higher-intensity
pulses, higher number of stimulation or longer treatment courses may be
more effective. Greater responsiveness to rTMS may be predicted by
several patients’ factors, including the absence of psychosis, younger
age and previous response to rTMS therapy.
DISCUSSION: Conclusions on these factors and others, such as the
importance of anatomically accurate coil placement and the distance from
the coil to the brain, await further investigation. Despite
heterogeneity of these reports according to methodology and treatment
parameters, the antidepressive properties of rTMS now appear obvious,
opening interesting prospects, in particular in the treatment of
pharmacoresistant major depressive patients and, we hope, administered
as adjuvant therapy in non-resistant depression.
CONCLUSION: Thus, many questions remain unanswered concerning the
optimal stimulation parameters, privileged indications and maintenance
sessions. This justifies the development of structured evaluation trials
on larger samples.
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
Abstract
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.
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.
Abstract
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.
| Biol Psychiatry. 2005 Mar 15;57(6):571-6. |
Antidepressant-like effects of cranial stimulation within a low-energy magnetic field in rats.
Carlezon WA Jr, Rohan ML, Mague SD, Meloni EG, Parsegian A, Cayetano K, Tomasiewicz HC, Rouse ED, Cohen BM, Renshaw PF.
Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA 02478, USA. carlezon@mclean.harvard.edu
BACKGROUND: Evidence suggests that a novel type of magnetic resonance
imaging (MRI) scan called echo planar magnetic resonance spectroscopic
imaging (EP-MRSI) has mood-elevating actions in humans during the
depressive phases of bipolar disorder. We examined whether a low-energy
component of EP-MRSI (low-field magnetic stimulation [LFMS]) has
antidepressant-like, locomotor-stimulating, or amnestic effects in rats.
METHODS: We examined the effects of LFMS on immobility in the forced
swim test (FST) and activity within an open field in separate groups of
rats. After exposure to forced swimming, rats received LFMS (three
20-min sessions at 1.5 G/cm and .75 V/m) before behavioral testing. We
also examined the effects of LFMS on fear conditioning (FC), a learning
paradigm that also involves exposure to stressful conditions. RESULTS:
Low-field magnetic stimulation reduced immobility in the FST, an
antidepressant-like effect qualitatively similar to that of standard
antidepressants. Low-field magnetic stimulation did not alter locomotor
activity or FC. CONCLUSIONS: Low-field magnetic stimulation has
antidepressant-like effects in rats that seem unrelated to
locomotor-activating or amnestic effects. These findings raise the
possibility that electromagnetic fields can affect the brain biology and
might have physiologic consequences that offer novel approaches to
therapy for psychiatric disorders. These same consequences might render
MRI-based scans more invasive than previously appreciated.
| 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.
Departments of aNeurology bPsychiatry and Psychotherapy cInstitute
for Experimental Physiology and Pathophysiology, University of Erlangen –
Nuremberg, Erlangen, Germany.
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.
| 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.
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.
| Prog Neuropsychopharmacol Biol Psychiatry. 2005 Oct 19; [Epub ahead of print] |
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.
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
</=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.
| Psychiatry Res. 2005 Nov 15;137(1-2):113-21. Epub 2005 Oct 11. |
Chronic repetitive transcranial magnetic stimulation is
antidepressant but not anxiolytic in rat models of anxiety and
depression.
Hargreaves GA, McGregor IS, Sachdev PS.
School of Psychiatry, University of New South Wales, Sydney, 2052,
Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Barker
Street, Randwick, NSW 2031, Australia.
Transcranial magnetic stimulation (TMS) has been proposed as a
treatment for depression and anxiety disorders. While the antidepressant
effect has been modelled in animals, there have been few attempts to
examine a possible anxiolytic effect of repetitive TMS (rTMS) in animal
models. We administered 18 days of rTMS to male Sprague-Dawley rats. On
days 10 through 18, rats were tested in several anxiety models (social
interaction, emergence, elevated plus-maze, and predator odor avoidance)
and in the forced swim test. No group differences were apparent on any
of the anxiety models, while TMS produced an antidepressant effect in
the forced swim test. Interestingly, on day 1 of the forced swim test,
the home cage control group displayed increased swimming behaviour
compared with sham-treated animals, suggesting an observable level of
stress may have accompanied sham treatment. The results from the forced
swim test suggested that TMS had modest antidepressant properties, but
it did not show anxiolytic properties in the models examined. The study
also suggested that stress associated with handling should be taken into
account in the interpretation of TMS studies in animals.
| Curr Psychiatry Rep. 2005 Oct;7(5):381-90. |
Transcranial magnetic stimulation for the treatment of depression in neurologic disorders.
Fregni F, Pascual-Leone A.
Beth Israel Deaconess Medical Center, Harvard Medical School, 330
Brookline Avenue, KS 452, Boston, MA 02215, USA.
ffregni@bidmc.harvard.edu.
Depression is commonly associated with neurologic disorders. Although
depression in neurologic conditions often is associated with a negative
impact on quality of life, it frequently is poorly managed. Some
factors, such as a multidrug regimen, lack of efficacy, and side effects
of antidepressants may explain why depression is not adequately treated
in patients with neurologic disorders. Therefore, this population needs
new approaches for depression treatment, and repetitive transcranial
magnetic stimulation (rTMS) may be one of them because it has been shown
to be effective for the treatment of depression alone and depression in
certain neurologic diseases such as Parkinson’s disease and stroke.
rTMS is a noninvasive, focal, and painless treatment associated with
few, mild side effects. It may be effective in the treatment of
neurologic diseases such as Parkinson’s disease, stroke, and epilepsy.
In this paper, we discuss the potential risks and benefits of rTMS
treatment for depression in Parkinson’s disease, epilepsy, stroke,
multiple sclerosis, and Alzheimer’s disease. Lastly, a framework that
includes the parameters of stimulation (intensity, frequency, number of
pulses, and site of stimulation) for the treatment of depression in
neurologic diseases is proposed.
| J Psychiatr Res. 2005 Oct 28; [Epub ahead of print] |
Striatal dopamine release after prefrontal repetitive
transcranial magnetic stimulation in major depression: Preliminary
results of a dynamic [(123)I] IBZM SPECT study.
Pogarell O, Koch W, Popperl G, Tatsch K, Jakob F, Zwanzger P, Mulert C, Rupprecht R, Moller HJ, Hegerl U, Padberg F.
Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstr. 7, D-80336 Munich, Germany.
Though there is considerable evidence that prefrontal repetitive
transcranial magnetic stimulation (rTMS) exerts antidepressant effects,
the neurobiological action of rTMS in patients with depression is poorly
understood. Preclinical studies in animals and humans have demonstrated
that prefrontal rTMS can induce dopamine release in mesostriatal and
mesolimbic regions. We therefore investigated whether rTMS also
modulates striatal dopaminergic neurotransmission in depressed patients
using a dynamic [(123)I] iodobenzamide (IBZM) single photon emission
computed tomography (SPECT) approach. Five patients with a major
depressive episode (DSM-IV) underwent an acute 10Hz rTMS challenge with
3000 stimuli over the left dorsolateral prefrontal cortex during an
[(123)I] IBZM-SPECT bolus and constant infusion protocol. In four
subjects the protocol was repeated after a three week rTMS standard
treatment. Striatal IBZM binding to dopamine D(2) receptors was assessed
with a region-of-interest (ROI) technique. The change in striatal IBZM
binding after the rTMS challenge was regarded as measure of change in
endogenous striatal dopamine. Data of nine SPECT investigations showed a
significant reduction by 9.6+/-6.2% in IBZM binding to striatal
dopamine D(2) receptors after rTMS challenge compared to baseline
(p=0.01, Wilcoxon test). In this preliminary study, the reduction of
IBZM binding observed after rTMS challenge is suggestive of a release in
endogenous dopamine induced by prefrontal rTMS. In future, this
approach can be used to differentiate specific and non-specific
reward-related effects of rTMS on dopaminergic neurotransmission.
| Rev Med Suisse. 2005 Sep 21;1(33):2162-4, 2166. |
[Novel brain stimulation techniques: therapeutic perspectives in psychiatry]
[Article in French]
Berney A, Vingerhoets F.
Service de psychiatrie de liaison, CHUV, 1011 Lausanne. Alexandre.Berney@chuv.ch
Recent advances have allowed the development of new physical
techniques in neurology and psychiatry, such as Transcranial Magnetic
Stimulation (TMS), Vagus Nerve Stimulation (VNS), and Deep Brain
Stimulation (DBS). These techniques are already recognized as
therapeutic approaches in several late stage refractory neurological
disorders (Parkinson’s disease, tremor, epilepsy), and currently
investigated in psychiatric conditions, refractory to medical treatment
(obsessive-compulsive disorder, resistant major depression). In
Paralell, these new techniques offer a new window to understand the
neurobiology of human behavior.
| Curr Psychiatry Rep. 2005 Oct;7(5):381-90. |
Transcranial magnetic stimulation for the treatment of depression in neurologic disorders.
Fregni F, Pascual-Leone A.
Beth Israel Deaconess Medical Center, Harvard Medical School, 330
Brookline Avenue, KS 452, Boston, MA 02215, USA.
ffregni@bidmc.harvard.edu.
Depression is commonly associated with neurologic disorders. Although
depression in neurologic conditions often is associated with a negative
impact on quality of life, it frequently is poorly managed. Some
factors, such as a multidrug regimen, lack of efficacy, and side effects
of antidepressants may explain why depression is not adequately treated
in patients with neurologic disorders. Therefore, this population needs
new approaches for depression treatment, and repetitive transcranial
magnetic stimulation (rTMS) may be one of them because it has been shown
to be effective for the treatment of depression alone and depression in
certain neurologic diseases such as Parkinson’s disease and stroke.
rTMS is a noninvasive, focal, and painless treatment associated with
few, mild side effects. It may be effective in the treatment of
neurologic diseases such as Parkinson’s disease, stroke, and epilepsy.
In this paper, we discuss the potential risks and benefits of rTMS
treatment for depression in Parkinson’s disease, epilepsy, stroke,
multiple sclerosis, and Alzheimer’s disease. Lastly, a framework that
includes the parameters of stimulation (intensity, frequency, number of
pulses, and site of stimulation) for the treatment of depression in
neurologic diseases is proposed.
| Exp Neurol. 2005 Sep 26; [Epub ahead of print] |
Repetitive transcranial magnetic stimulation of the
dorsolateral prefrontal cortex and cortical excitability in patients
with major depressive disorder.
Bajbouj M, Brakemeier EL, Schubert F, Lang UE, Neu P, Schindowski C, Danker-Hopfe H.
Department of Psychiatry, Charite-University Medicine Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany.
Repetitive transcranial magnetic stimulation (rTMS) of the
dorsolateral prefrontal cortex is a relatively non-invasive technique
with putative therapeutic effects in major depression. However, the
exact neurophysiological basis of these effects needs further
clarification. Therefore, we studied the impact of ten daily sessions of
left, dorsolateral prefrontal rTMS on motor cortical excitability, as
revealed by transcranial magnetic stimulation-elicited motor-evoked
potentials in 30 patients. As compared to the non-responders, responders
(33%) showed changes in parameters pointing towards a reduced cortical
excitability. These results suggest that repetitive transcranial
magnetic stimulation of the dorsolateral, prefrontal cortex may have
inhibitory effects on motor cortical neuronal excitability in patients
with major depressive disorder. Furthermore, measurement of motor
cortical excitability may be a useful tool for investigating and
monitoring inhibitory brain effects of antidepressant stimulation
techniques like rTMS.
| Epilepsy Behav. 2005 Sep;7(2):182-9. |
Transcranial magnetic stimulation treatment for epilepsy: can it also improve depression and vice versa?
Fregni F, Schachter SC, Pascual-Leone A.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. ffregni@bidmc.harvard.edu
Comorbidity with depression is an important determinant of the
quality of life for patients with epilepsy. Antidepressant medications
can effectively treat depression in epileptic patients, but drug-drug
interactions and epileptogenic effects of these drugs pose therapeutic
challenges. The mood-stabilizing effects of antiepileptic medications
may not be sufficient to treat depression. Therefore, treatments that
alleviate the burden of depression without increasing seizure risk or,
better yet, with the possibility of improving seizure control are worth
exploring. Neuroimaging techniques, such as functional magnetic
resonance imaging, are providing novel insights into the pathophysiology
of depression in epilepsy. For example, there appears to be prominent
brain prefrontal hypoactivity, which may be sustained by the
hyperactivity of the seizure focus. If so, neuromodulatory approaches
that suppress epileptic focus hyperactivity and concurrently enhance
prefrontal activity may be ideally suited. Indeed, vagus nerve
stimulation has been shown to yield simultaneous antiseizure and mood
effects. Another neuromodulatory technique, transcranial magnetic
stimulation (TMS), can also modulate brain activity, but in a
noninvasive, painless, and focal manner. Depending on the stimulation
parameters, it is possible to enhance or reduce activity in the targeted
brain region. Furthermore, TMS has been shown to be effective in
treating depression, and preliminary data suggest that this treatment
may also be effective for epilepsy treatment. This article reviews these
data and explores further the question of whether depression and
epilepsy can be simultaneously treated with TMS for optimal therapeutic
impact.
| 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.
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.
| Neuro Endocrinol Lett. 2005 Aug 30;26(4) [Epub ahead of print] |
Repetitive transcranial magnetic stimulation in a patient
suffering from depression and rheumatoid arthritis: Evidence for
immunmodulatory effects.
Langguth B, Braun S, Aigner JM, Landgrebe M, Weinerth J, Hajak G, Eichhammer P.
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Regensburg, Germany. Berthold.Langguth@medbo.de.
Repetitive transcranial magnetic stimulation (rTMS) has been
suggested as antidepressive treatment strategy [1]. The mechanism of
action by which the antidepressive effect is brought about remains
unclear at present. Here, we report findings in a patient suffering from
recurrent major depression and rheumatoid arthritis. Improvement of
depressive symptoms during 20 Hz rTMS of the left dorsolateral
prefrontal cortex was repeatedly associated with a systemic inflammatory
reaction, suggesting that rTMS induced an immunmodulatory effect.
| 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. kenichi3@sd5.so-net.ne.jp
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.
| Seizure. 2005 Sep;14(6):387-92. |
Low-frequency repetitive transcranial magnetic stimulation
for seizure suppression in patients with extratemporal lobe epilepsy-a
pilot study.
Kinoshita M, Ikeda A, Begum T, Yamamoto J, Hitomi T, Shibasaki H.
Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan.
We evaluated the effect of low-frequency repetitive transcranial
magnetic stimulation (rTMS) on seizure frequency in adult patients with
medically intractable extratemporal lobe epilepsy (ETLE). Seven patients
with medically intractable ETLE received low-frequency rTMS at 0.9 Hz,
basically two sets of 15 min stimulation per day for five days in a
week, with the stimulus intensity of 90% of resting motor threshold
(RMT). The number of seizures during two weeks before and after the
stimulation of one week was compared. Furthermore, RMT and active motor
threshold (AMT) were measured before and after rTMS for each daily
session. After low-frequency rTMS of one week, the frequency of all
seizure types, complex partial seizures (CPSs) and simple partial
seizures was reduced by 19.1, 35.9 and 7.4%, respectively. The patients
with smaller difference between RMT and AMT before rTMS had higher
reduction rate of CPSs. A favorable tendency of seizure reduction,
though not statistically significant, during two weeks after
low-frequency rTMS was demonstrated in medically intractable ETLE
patients. As far as CPSs are concerned, smaller decrease of motor
threshold by voluntary muscle contraction was associated with better
response to rTMS.
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 São Paulo, Faculty of Medicine, São Paulo-SP, Brazil. drumi@usp.br
Abstract
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.
Transcranial magnetic stimulation in persons younger than the age of 18.
Quintana H.
Department of Psychiatry, Division of Child and Adolescent
Psychiatry, Louisiana State University Health Science Center, School of
Medicine, New Orleans, Louisiana 70112-2822, USA. Hquint@lsuhsc.edu
OBJECTIVES: To review the use of transcranial magnetic stimulation
(single-pulse TMS, paired TMS, and repetitive TMS [rTMS]) in persons
younger than the age of 18 years. I discuss the technical differences,
as well as the diagnostic, therapeutic, and psychiatric uses of TMS/rTMS
in this age group. METHODS: I evaluated English-language studies from
1993 to August 2004 on nonconvulsive single-pulse, paired, and rTMS that
supported a possible role for the use of TMS in persons younger than
18. Articles reviewed were retrieved from the MEDLINE database and
Clinical Scientific index. RESULTS: The 48 studies reviewed involved a
total of 1034 children ages 2 weeks to 18 years; 35 of the studies used
single-pulse TMS (980 children), 3 studies used paired TMS (20
children), and 7 studies used rTMS (34 children). Three studies used
both single and rTMS. However, the number of subjects involved was not
reported. CONCLUSIONS: Single-pulse TMS, paired TMS, and rTMS in persons
younger than 18 has been used to examine the maturation/activity of the
neurons of various central nervous system tracts, plasticity of neurons
in epilepsy, other aspects of epilepsy, multiple sclerosis, myoclonus,
transcallosal inhibition, and motor cortex functioning with no reported
seizure risk. rTMS has been applied to psychiatric disorders such as
ADHD, ADHD with Tourette’s, and depression. Adult studies support an
antidepressant effect from repetitive TMS, but there is only one study
that has been reported on 7 patients that used rTMS to the left dorsal
prefrontal cortex on children/adolescents with depression (5 of the 7
subjects treated responded). Although there are limited studies using
rTMS (in 34 children), these studies did not report significant adverse
effects or seizures. Repetitive TMS safety, ethical, and neurotoxicity
concerns also are discussed.
| Neuron. 2005 Jan 20;45(2):181-3. |
Toward establishing a therapeutic window for rTMS by theta burst stimulation.
Paulus W.
Department of Clinical Neurophysiology, University of Goettingen, D-37075 Goettingen, Germany.
In this issue of Neuron, Huang et al. show that a version of the
classic theta burst stimulation protocol used to induce LTP/LTD in brain
slices can be adapted to a transcranial magnetic stimulation (TMS)
protocol to rapidly produce long lasting (up to an hour), reversible
effects on motor cortex physiology and behavior. These results may have
important implications for the development of clinical applications of
rTMS in the treatment of depression, epilepsy, Parkinson’s, and other
diseases.
| Psychiatry Res. 2005 Oct 10; [Epub ahead of print] |
Chronic repetitive transcranial magnetic stimulation is
antidepressant but not anxiolytic in rat models of anxiety and
depression.
Hargreaves GA, McGregor IS, Sachdev PS.
School of Psychiatry, University of New South Wales, Sydney, 2052,
Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Barker
Street, Randwick, NSW 2031, Australia.
Transcranial magnetic stimulation (TMS) has been proposed as a
treatment for depression and anxiety disorders. While the antidepressant
effect has been modelled in animals, there have been few attempts to
examine a possible anxiolytic effect of repetitive TMS (rTMS) in animal
models. We administered 18 days of rTMS to male Sprague-Dawley rats. On
days 10 through 18, rats were tested in several anxiety models (social
interaction, emergence, elevated plus-maze, and predator odor avoidance)
and in the forced swim test. No group differences were apparent on any
of the anxiety models, while TMS produced an antidepressant effect in
the forced swim test. Interestingly, on day 1 of the forced swim test,
the home cage control group displayed increased swimming behaviour
compared with sham-treated animals, suggesting an observable level of
stress may have accompanied sham treatment. The results from the forced
swim test suggested that TMS had modest antidepressant properties, but
it did not show anxiolytic properties in the models examined. The study
also suggested that stress associated with handling should be taken into
account in the interpretation of TMS studies in animals.
| Psychiatr Pol. 2004 Mar-Apr;38(2):217-25. |
[Estimation of therapeutical efficacy of weak variable magnetic fields with low value of induction in patients with depression]
[Article in Polish]
Sieron A, Hese RT, Sobis J, Cieslar G.
Z Katedry i Kliniki Chorob Wewnetrznych i Medycyny Fizykalnej Wydzialu Lekarskiego w Zabrzu Slaskiej AM w Katowicach.
AIM: Preliminary results of research on the therapeutical efficacy of
weak variable magnetic fields with low value of induction used as
magnetostimulation in patients with depression not reacting to two
consecutive, correctly applied anti-depressant pharmacological treatment
are presented in the paper. METHOD: The examined patients (24 persons
aged 18-65 years) treated with anti-depressants accessible in Poland
were randomly divided into 2 groups. In 1 group (11 persons–9 women and 2
men) magnetostimulation with the use of a weak variable magnetic field
with a low value of induction of 15 microT generated by the VIOFOR JPS
device (Poland) lasting 12 minutes daily for 15 days was added to
pharmacological therapy. Patients from 2 groups (13 persons–11 women and
2 men) were exposed to exposure with the same device. The intensity of
depression was estimated with Beck’s, Montgomery-Asberg’s and Hamilton’s
scales. RESULTS: As a result of a cycle of active magnetostimulation a
distinct, statistically significant decrease of intensification of
depression, both in the 7th and 15th day exposure was obtained, while in
the sham-exposed group only slight, transient decrease of
intensification of depression in the 7th day of sham-exposure was
observed. CONCLUSIONS: It was concluded that adding magnetostimulation
to pharmacological therapy results in a progressive, significant
reduction of intensification of depression symptoms.
| Psychiatry Res. 2005 Oct 11; [Epub ahead of print] |
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.
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.
| Bipolar Disord. 2005;7 Suppl 5:13-23. |
Newer treatment studies for bipolar depression.
Gao K, Calabrese JR.
NIMH Bipolar Research Center, Mood Disorders Program, University
Hospitals of Cleveland/Case Western Reserve University School of
Medicine, Cleveland, OH, USA.
Objective: Depressive symptoms of bipolar disorder have more negative
impact on a patient’s life than manic symptoms. This review focused on
the emerging efficacy data for treatments in bipolar depression.
Methods: English-language literature cited in Medline was searched with
terms bipolar depression, clinical trial, and trial. Randomized,
placebo-controlled trials of newer studies with older agents and all
studies with newer or novel agents were prioritized. Open-label studies
of novel agents presented at major scientific meetings were also
included. Results: Olanzapine, olanzapine-fluoxetine combination (OFC),
and quetiapine were superior to placebo in the acute treatment of
bipolar depression. Lamotrigine only significantly reduced core symptoms
of depression compared with placebo. Pramipexole, a dopamine D2/D3
receptor agonist and omega-3 fatty acids, a polyunsaturated fatty acid,
augmentation to mood stabilizer (MS) had superiority to placebo in
reducing depressive symptoms. Topiramate augmentation of an MS was
equally as effective as Bupropion-SR. Patients treated with an MS
responded well to the addition of agomelatine, a melatonin receptor
agonist with 5-HT2C antagonist properties. However, inositol and
repetitive transcranial magnetic stimulation did not separate from
placebo. Lamotrigine and olanzapine, and to a lesser extent, divalproex,
are superior to placebo in preventing depressive relapses. All agents
were relatively well tolerated. Conclusions: Olanzapine, OFC, and
quetiapine are effective in the acute treatment of bipolar depression.
Compared with lithium and divalproex, lamotrigine is more effective in
preventing bipolar depression. Larger controlled studies of the other
agents in the acute and maintenance treatment of bipolar depression are
warranted.
| Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99(10):26-9. |
[Transcranial magnetic stimulation in neurotic depression]
[Article in Russian]
Stikhina NIa, Lyskov EB, Lomarev MP, Aleksanian ZA, Mikhailov VO, Medvedev SV.
Transcranial magnetic stimulation (TMS) was applied in combination
with psychotherapy in patients with neurotic depression, including 15
patients of the experimental group and 14 patients of the control one.
10 sessions of daily TMS for the patients from the experimental group
(0.015 T, 40 pulses per sec) were performed at the same time for 20 min
(twice for 10 min with 5-min interval) in a room which excluded any
external stimulation. TMS was performed by contact method: 5 cm coil was
applied to the left prefrontal area. The control group received the
imitation of TMS-procedure stimulation. The improvement of mental state
was in 13 patients of experimental group and in 3 of control one. The
course of TMS resulted in a significant attenuation of depression by the
Hamilton Depression Rating scale (from 22.9 to 8.6) and the Anxiety
Inventory (from 39.4 to 26.6), that was significantly higher in
comparison with the control. There weren’t found any TMS-related changes
in blood pressure and pulse rate as well as any pathological EEG
symptoms.
| Biomed Sci Instrum. 2003;39:466-70. |
Autoradiographic evaluation of electromagnetic field effects on serotonin (5HT1A) receptors in rat brain.
Johnson MT, McCullough J, Nindl G, Chamberlain JK.
Terre Haute Center for Medical Education, Indiana University School of Medicine, Terre Haute, IN 47809, USA.
Serotonin (5HT1A) is a chemical mediator of inflammation and the
largest single neurotransmitter system of the brain. Its secretion and
physiological actions mediate stress and pain, affecting both immune and
nervous system functions through the hypothalamic-pituitary-adrenal
axis. Serotonin receptor dysfunction is well-characterized in mental
disturbances like depression and anxiety. Transcranial magnetic
stimulation has been used therapeutically to treat refractory disorders
like non-responsive depression and may act in part through its effect on
5HT1A receptors. Previously we have shown that in vitro, 5HT1A receptor
binding to a radioactive agonist can be modulated by specific intensity
and frequency electromagnetic fields (EMFs). In the present report we
have used quantitative receptor autoradiography to evaluate 5HT1A
receptor density in rat brain and the impact of pulsed EMF exposure on
receptor binding in key brain regions. Rats used in this study had whole
body exposures to either a geofield control or to pulsed EMFs to
evaluate the treatment for chemically-induced tendinitis. Since the
brains were exposed coincidentally as a consequence of the main
experiment, we investigated the potential for EMF-induced changes in
areas such as the hippocampus. This pilot study should provide a
detailed understanding of magnetic field effects on stress-responsive
brain regions and will lead to a more coordinated approach to the use of
such modalities for therapeutic intervention in humans.
| Fortschr Neurol Psychiatr. 2001 Sep;69(9):402-9. |
[Which patients with major depression benefit from prefrontal repetitive magnetic stimulation]
[Article in German]
Eschweiler GW, Plewnia C, Bartels M.
Universitatsklinik fur Psychiatrie und Psychotherapie Tubingen. eschweiler@med.uni-tuebingen.de
Antidepressive benefit of prefrontal repetitive magnetic stimulation
(RTMS) for one or two weeks varies between 6 % and 60 % (mean 37 %)
improvement of the Hamilton depression scale vs. 12 % improvement
following sham RTMS. This variance is probably caused by study specific
stimulus parameters but also by genetic, psychopathological and
neuropsychological characteristics of the patients as well as by the
functional state of the cortex area below the stimulation coil.Data from
10 open and 7 sham controlled studies including two own studies
comprising more than 300 patients with major depression have been
published to date. In synopsis several positive predictors for
antidepressive response of prefrontal RTMS become apparent: 1) younger
age, 2) somatic signs of anxiety, 3) lack of cortical hyperactivity
below the magnetic coil pulsed by 10 Hz stimuli, 4) cortical
hypermetabolism below the 1 Hz pulsed coil.Negative predictors of
response to prefrontal RTMS were: 1) Advanced age, 2) prefrontal
atrophy, 3) cognitive impairment in neuropsychological tasks assigned to
the prefrontal cortex, 4) psychotic symptoms, 5) cortical hyperactivity
below 10 Hz pulsed coil 6) non-response to electroconvulsive therapy
(ECT).While prefrontal RTMS will probably not replace ECT in severe
major depression with psychotic symptoms it could be beneficial
especially in younger anxious patients without cognitive impairment.
| Nord J Psychiatry. 2003;57(3):227-32. |
Efficacy of repetitive transcranial magnetic stimulation in depression: a review of the evidence.
Aarre TF, Dahl AA, Johansen JB, Kjonniksen I, Neckelmann D.
Nordfjord Psychiatric Centre, N-6770 Nordfjordeid, Norway. trond.aarre@helse-forde.no
Repetitive transcranial magnetic stimulation (rTMS) is a novel
treatment in psychiatry. We reviewed all published evidence on the
efficacy of this treatment option in depressive disorders. An extensive
electronic and manual search for eligible research reports identified
only 12 studies that met the predetermined criteria for inclusion. rTMS
was administered differently in most studies, and patient
characteristics varied widely. A formal meta-analysis of the studies was
thus not possible. Instead, we conducted a qualitative evaluation of
the included studies. The antidepressive efficacy was not consistent,
and where efficacy was demonstrated, it was modest in most studies. Some
patients had good but transient responses to rTMS. Treatment gains were
not maintained beyond the treatment period. Comparisons with
electroconvulsive therapy (ECT) indicated the superiority of ECT. More,
larger and more carefully designed studies are needed to demonstrate
convincingly a clinically relevant effect of rTMS. We conclude that
there is insufficient evidence for rTMS as a valid treatment for
depression at present.
| Int J Neurosci. 1996 Oct;87(1-2):5-15. |
Suicidal behavior is attenuated in patients with multiple sclerosis by treatment with electromagnetic fields.
Sandyk R.
NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.
A marked decrease in the levels of serotonin (5-HT) and its
metabolite (5-HIAA) has been demonstrated in postmortem studies of
suicide victims with various psychiatric disorders. Depression is the
most common mental manifestation of multiple sclerosis (MS) which
accounts for the high incidence of suicide in this disease. CSF 5-HIAA
concentrations are reduced in MS patients and nocturnal plasma melatonin
levels were found to be lower in suicidal than in nonsuicidal patients.
These findings suggest that the increased risk of suicide in MS
patients may be related to decreased 5-HT functions and blunted
circadian melatonin secretion. Previous studies have demonstrated that
extracerebral applications of pulsed electromagnetic fields (EMFs) in
the picotesla range rapidly improved motor, sensory, affective and
cognitive deficits in MS. Augmentation of cerebral 5-HT synthesis and
resynchronization of circadian melatonin secretion has been suggested as
a key mechanism by which these EMFs improved symptoms of the disease.
Therefore, the prediction was made that this treatment modality would
result in attenuation of suicidal behavior in MS patients. The present
report concerns three women with remitting-progressive MS who exhibited
suicidal behavior during the course of their illness. All patients had
frequent suicidal thoughts over several years and experienced resolution
of suicidal behavior within several weeks after introduction of EMFs
treatment with no recurrence of symptoms during a follow-up of months to
3.5 years. These findings demonstrate that in MS pulsed applications of
picotesla level EMFs improve mental depression and may reduce the risk
of suicide by a mechanism involving the augmentation of 5-HT
neurotransmission and resynchronization of circadian melatonin
secretion.
| Percept Mot Skills. 1996 Oct;83(2):491-8. |
Weak, but complex pulsed magnetic fields may reduce depression following traumatic brain injury.
Baker-Price LA, Persinger MA.
Department of Psychology, Laurentian University, Sudbury, Ontario, Canada.
Many patients who display psychological depression following a
traumatic brain injury do not respond completely to antidepressant
drugs. We hypothesized that this type of depression is strongly
correlated with subclinical, complex partial seizure-activity within the
hippocampal-amygdaloid region that continues for months to years after
apparent neurological and behavioral “recovery.” Four depressed patients
who had sustained traumatic brain injuries and who exhibited mild to
moderate brain impairment according to standardized tests received 30
min. of weak (1 microT) burst-firing magnetic fields across the temporal
lobes once per week for 5 weeks. There was a significant improvement of
depression and reduction of phobias while physical symptoms and other
complaints were not changed
| Pol J Pharmacol. 2002 Nov-Dec;54(6):633-9. |
Effect of combined treatment with paroxetine and transcranial
magnetic stimulation (TMS) on the mitogen-induced proliferative
response of rat lymphocytes.
Roman A, Vetulani J, Nalepa I.
Laboratory of Intracellular Signalling, Department of Biochemistry,
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL
31-343 Krakow, Poland. roman@if-pan.krakow.pl
Depression is associated with abnormal functions of the immune
system. In this study, we investigated how two modem antidepressant
therapies, chronic treatment with transcranial magnetic stimulation
(TMS) and administration of an antidepressant belonging to selective
serotonin reuptake inhibitors (SSRI), paroxetine, affect the
proliferative response of thymocytes and splenocytes stimulated in vitro
with various mitogens. Paroxetine (10 mg/kg) and TMS (B = 1.2 T, f = 30
Hz, t = 330 s) were applied once daily for 12 consecutive days, while,
if given jointly paroxetine was injected 30 min before TMS. The mitogens
used were: concanavalin A (Con A), pokeweed mitogen (PWM) or
lipopolysaccharide (LPS). While either treatment applied alone had no
effect on proliferative response, the joint application of paroxetine
and TMS significantly depressed it. The literature data suggest that
pulsed magnetic field may directly inhibit mitogen-activated lymphocyte
proliferation, which is also inhibited by the presence of high level of
serotonin. The present results suggest that both effects are additive,
and because of that application of both treatments, whose effects alone
are insufficient to prompt the reaction, possibly because adaptive
changes during chronic treatment, results in a significant inhibition of
lymphocyte proliferation.
| Epilepsy Behav. 2003 Oct;4 Suppl 3:S46-54. |
Treatment of depression in patients with epilepsy: problems, pitfalls, and some solutions.
Krishnamoorthy ES.
T.S. Srinivasan Institute of Neurological Sciences and Research,
Public Health Centre, Chennai, India. E.S.Krishnamoorthy@ion.ucl.ac.uk
Many people with epilepsy suffer from comorbid depression. Despite
this, there have been few studies addressing the treatment of depression
in this population, and the literature on psychiatric management
techniques in patients with epilepsy is composed largely of opinions
rather than evidence from randomized, controlled trials or other
systematic investigations. Antidepressant drugs, including tricyclics
and selective serotonin reuptake inhibitors, can be used to treat
patients with epilepsy and comorbid depression. Nonpharmacological
treatment options include vagus nerve stimulation, transcranial magnetic
stimulation, and psychological therapies including cognitive-behavioral
therapy, individual or group psychotherapy, patient support groups,
family therapy, and counseling. Another important area that remains
largely uninvestigated is psychiatric research in patients with epilepsy
in non-Western cultures (with the exception of Japan). Factors such as
problems with access to and acceptability of therapies in many
developing nations have further implications for the treatment of
psychiatric disorders in epilepsy.