The effects of repetitive transcranial magnetic stimulation on depressive symptoms and the P(300) event-related potential

Changes in the Hamilton Depression Rating Scale and the P(300) auditory event-related potential were assessed in 10 patients with depression before and after a treatment course of five daily sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex. The patients were initially randomly allocated either to an active or a placebo rTMS treatment. All patients received both types of treatment separated by an interval of 4 weeks. The median Hamilton score decreased by 7 points following active rTMS and by 1 point after sham (p=0.075). Active rTMS was associated with a significant increase in the P(300) amplitude compared with sham (p=0.02). There was no correlation between changes in P(300) measurements and the Hamilton scores after active treatment. We conclude that five daily sessions of left prefrontal rTMS treatment is not of sufficient duration to make a significant improvement in depressive symptoms.     

Long-lasting effects of high frequency repetitive transcranial magnetic stimulation in major depressed patients

The majority of previous clinical studies have indicated that repetitive transcranial magnetic stimulation (rTMS) may have antidepressant effects. Herein, we investigated the longitudinal, long-term antidepressant efficacy of daily left prefrontal cortex (PFC) rTMS for a 1-week period. Nineteen patients were randomly assigned to two treatment groups at 90% of individual motor threshold (MT): Twelve received active repetitive transcranial magnetic stimulation and seven received sham treatment. Each patient underwent five sessions of twenty 2-s trains of 20 Hz rTMS with 800 stimuli/day. The Beck Depression Inventory and the Hamilton Depression Rating Scale were used to assess severity of depression at 1, 4 and 12 weeks post-therapy. A significant reduction of baseline depression scores was observed after 1 week of active treatment that lasted for 1 month, indicating improvement of depressive symptoms. No significant effects were observed in patients receiving sham treatment. The results of this controlled study are in agreement with the findings of previous studies suggesting that daily left PFC rTMS has an antidepressant effect.     

Acute mood and thyroid stimulating hormone effects of transcranial magnetic stimulation in major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has recently been demonstrated to have antidepressant effects. Some work suggests that rTMS over prefrontal cortex administered to healthy individuals produces acute elevations of mood and serum thyroid-stimulating hormone (TSH). We sought to determine whether single rTMS sessions would produce acute mood and serum TSH elevations in subjects with major depressions. METHODS: Under double-blind conditions et al 14 medication-free subjects with major depression received individual sessions of either active or sham rTMS. rTMS was administered over the left prefrontal cortex at 10 Hz et al 100% of motor threshold, 20 trains over 10 min. Immediately before and after rTMS sessions, subjects' mood was rated with the Profile of Mood States (POMS) and the 6-Item Hamilton Depression Scale, and blood was drawn for later analysis of TSH. Subjects and raters were blind to treatment assignment. RESULTS: The group receiving active stimulation manifested significantly greater improvement on the POMS subscale of Depression (p < or = .0055) and a trend toward greater improvement on the modified Hamilton Rating (.05 < p < or =.1). No hypomania was induced. The change in TSH from pre- to post-rTMS was significantly different between active and sham sessions. CONCLUSIONS: This blinded, placebo-controlled trial documents that individual rTMS sessions can acutely elevate mood and stimulate TSH release in patients experiencing major depressive episodes.     

Localized Potentiation of Sleep Slow-Wave Activity Induced by Prefrontal Repetitive Transcranial Magnetic Stimulation in Patients with a Major Depressive Episode

BackgroundThe effects of repetitive transcranial magnetic stimulation (rTMS) on sleep structure in major depression are currently unknown.ObjectiveTo determine the effects of prefrontal rTMS on sleep electroencephalography (EEG) in major depression.MethodsIn this open-label pilot study, twelve male patients with relatively mild depression, who had been medication-resistant, underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). Polysomnographic (PSG) data were recorded over four nights: Adaptation, Baseline, Post-1 (after the fifth rTMS session), and Post-2 (after the tenth rTMS session). Discrete Fourier Transform (DFT) band power analyses were performed to quantify delta and sigma band activities during Stages II–IV, and determine time courses of these activities between Baseline and Post-1 (first five sessions) and between Post-1 and Post-2 (last five sessions).ResultsPost-hoc tests based on a three-way ANOVA model indicated significant delta power increase at F3 (t₁₁ = ?2.762, P = 0.018) during the first five sessions; however, sigma power was unchanged. No significant band power changes were observed during the second half. Stages II–IV (percent total sleep time) increased significantly during the first half (t₁₂ = ?2.43, P = 0.033). No other significant changes in sleep parameters or clinical correlations were observed.ConclusionsThe first five sessions of high frequency rTMS to the left DLPFC increase slow-wave activity (SWA) at F3, possibly reflecting locally enhanced synaptic plasticity induced by rTMS. This increased activity was not observed during the last half, possibly due to a homeostatic regulation mechanism intrinsic to SWA.     

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression

Abstract

Background and aim: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD).

Methods: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10?Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1?Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks.

Results: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression.

Conclusions: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.     

The Painfulness of Active,but not Sham,Transcranial Magnetic Stimulation Decreases Rapidly Over Time: Results From the Double-Blind Phase of the OPT-TMS Trial

BackgroundDaily left prefrontal repetitive transcranial magnetic stimulation (rTMS) over several weeks is an FDA approved treatment for major depression. Although rTMS is generally safe when administered using the FDA guidelines, there are a number of side effects that can make it difficult for patients to complete a course of rTMS. Many patients report that rTMS is painful, although patients appear to accommodate to the initial painfulness. The reduction in pain is hypothesized to be due to prefrontal stimulation and is not solely explained by accommodation to the stimulation.MethodsIn a recent 4 site randomized controlled trial (using an active electrical sham stimulation system) investigating the antidepressant effects of daily left dorsolateral prefrontal rTMS (Optimization of TMS, or OPT-TMS), the procedural painfulness of TMS was assessed before and after each treatment session. Computerized visual analog scale ratings were gathered before and after each TMS session in the OPT-TMS trial. Stimulation was delivered with an iron core figure-8 coil (Neuronetics) with the following parameters: 10 Hz, 120% MT (EMG-defined), 4 s pulse train, 26 s inter-train interval, 3000 pulses per session, one 37.5 min session per day. After each session, procedural pain (pain at the beginning of the TMS session, pain toward the middle, and pain toward then end of the session) ratings were collected at all 4 sites. From the 199 patients randomized, we had usable data from 142 subjects for the initial 15 TMS sessions (double-blind phase) delivered over 3 weeks (142 × 2 × 15 = 4260 rating sessions).ResultsThe painfulness of real TMS was initially higher than that of the active sham condition. Over the 15 treatment sessions, subjective reports of the painfulness of rTMS (during the beginning, middle and end of the session) decreased significantly 37% from baseline in those receiving active TMS, with no change in painfulness in those receiving sham. This reduction, although greatest in the first few days, continued steadily over the 3 weeks. Overall, there was a decay rate of 1.56 VAS points per session in subjective painfulness of the procedure in those receiving active TMS.DiscussionThe procedural pain of left, prefrontal rTMS decreases over time, independently of other emotional changes, and only in those receiving active TMS. These data suggest that actual TMS stimulation of prefrontal cortex maybe related to the reduction in pain, and that it is not a non-specific accommodation to pain. This painfulness reduction softly corresponds with later clinical outcome. Further work is needed to better understand this phenomenon and whether acute within-session or over time painfulness changes might be used as short-term biomarkers of antidepressant response.     

A Two-site Pilot Randomized 3 Day Trial of High Dose Left Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) for Suicidal Inpatients

BackgroundSuicide attempts and completed suicides are common, yet there are no proven acute medication or device treatments for treating a suicidal crisis. Repeated daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) for 4–6 weeks is a new FDA-approved treatment for acute depression. Some open-label rTMS studies have found rapid reductions in suicidality.DesignThis study tests whether a high dose of rTMS to suicidal inpatients is feasible and safe, and also whether this higher dosing might rapidly improve suicidal thinking. This prospective, 2-site, randomized, active sham-controlled (1:1 randomization) design incorporated 9 sessions of rTMS over 3 days as adjunctive to usual inpatient suicidality treatment. The setting was two inpatient military hospital wards (one VA, the other DOD).PatientsResearch staff screened approximately 377 inpatients, yielding 41 adults admitted for suicidal crisis. Because of the funding source, all patients also had either post-traumatic stress disorder, mild traumatic brain injury, or both.TMS methodsRepetitive TMS (rTMS) was delivered to the left prefrontal cortex with a figure-eight solid core coil at 120% motor threshold, 10 Hertz (Hz), 5 second (s) train duration, 10 s intertrain interval for 30 minutes (6000 pulses) 3 times daily for 3 days (total 9 sessions; 54,000 stimuli). Sham rTMS used a similar coil that contained a metal insert blocking the magnetic field and utilized electrodes on the scalp, which delivered a matched somatosensory sensation.Main outcome measurePrimary outcomes were the daily change in severity of suicidal thinking as measured by the Beck Scale of Suicidal Ideation (SSI) administered at baseline and then daily, as well as subjective visual analog scale measures before and after each TMS session. Mixed model repeated measures (MMRM) analysis was performed on modified intent to treat (mITT) and completer populations.ResultsThis intense schedule of rTMS with suicidal inpatients was feasible and safe. Minimal side effects occurred, none differing by arm, and the 3-day retention rate was 88%. No one died of suicide within the 6 month followup. From the mITT analyses, SSI scores declined rapidly over the 3 days for both groups (sham change −15.3 points, active change −15.4 points), with a trend for more rapid decline on the first day with active rTMS (sham change −6.4 points, active −10.7 points, P = 0.12). This decline was more pronounced in the completers subgroup [sham change −5.9 (95% CI: −10.1, −1.7), active −13 points (95% CI: −18.7, −7.4); P = 0.054]. Subjective ratings of ‘being bothered by thoughts of suicide’ declined non-significantly more with active rTMS than with sham at the end of 9 sessions of treatment in the mITT analysis [sham change −31.9 (95% CI: −41.7, −22.0), active change −42.5 (95% CI: −53.8, −31.2); P = 0.17]. There was a significant decrease in the completers sample [sham change −24.9 (95% CI: −34.4, −15.3), active change −43.8 (95% CI: −57.2, −30.3); P = 0.028].ConclusionsDelivering high doses of left prefrontal rTMS over three days (54,000 stimuli) to suicidal inpatients is possible and safe, with few side effects and no worsening of suicidal thinking. The suggestions of a rapid anti-suicide effect (day 1 SSI data, Visual Analogue Scale data over the 3 days) need to be tested for replication in a larger sample.Trial registrationClinicalTrials.gov Identifier: NCT01212848, TMS for suicidal ideation.     

The Efficacy and Safety of Low Frequency Repetitive Transcranial Magnetic Stimulation for Treatment-resistant Depression: The Results From a Large Multicenter French RCT

ContextThe aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150–225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD).MethodIn a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n = 55), active rTMS combined with placebo venlafaxine (n = 60) or sham rTMS combined with active venlafaxine (n = 55). The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS₁₇ score <8.ResultsWe reported a similar significant antidepressant effect in the 3 groups (P < 10⁻⁶), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; P = 0.59).ConclusionLow frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 min) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.     

Antidepressant Efficacy of High and Low Frequency rTMS at 110% of Motor Threshold versus Sham Stimulation over Left Prefrontal Cortex

BackgroundWhile the efficacy of repetitive transcranial magnetic stimulation (rTMS) at 10 Hz over the left prefrontal cortex has been repeatedly demonstrated, it is not clear that the optimal parameters for the treatment of depression have been adequately elucidated.ObjectivesWe sought to assess the antidepressant effectiveness of high and low frequency at a higher intensity rTMS compared to sham in patients with moderately treatment resistant depression.MethodThe authors conducted a three-week, double-blind, randomized, sham-controlled study of 24 acutely depressed patients given either active 20 Hz (n = 8) or 1 Hz (n = 8) rTMS (at 110% of motor threshold [MT]) or sham treatments (n = 8) over the left prefrontal cortex. Hamilton Depression ratings were analyzed by ANOVA.ResultsPatients on both frequencies showed greater improvement than on sham, which was associated with minor increases in depression. During open continuation to allow 7 weeks of active treatment in all individuals, additional improvement was observed.ConclusionsThe results seen here using 110% of MT for 3 weeks were more robust than those of previous studies of 1-Hz or 20-Hz rTMS for 2 weeks (at 80% and 100% of MT). The results also raise the possibility that both high and low frequency rTMS over left prefrontal cortex (and not just low frequency over the right prefrontal cortex) exert antidepressant effects, but further work is required to assess what parameters may be most effective in general and for a given individual.     

Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia

The aim of the study was to compare the long-term efficacy of high versus low frequency repetitive transcranial magnetic stimulation (rTMS), applied bilaterally over the dorsolateral prefrontal cortex (DLPFC), on cognitive function and cortical excitability of patients with Alzheimer's disease (AD). Forty-five AD patients were randomly classified into three groups. The first two groups received real rTMS over the DLPFC (20 and 1 Hz, respectively) while the third group received sham stimulation. All patients received one session daily for five consecutive days. In each session, rTMS was applied first over the right DLPFC, immediately followed by rTMS over the left DLPFC. Mini Mental State Examination (MMSE), Instrumental Daily Living Activity (IADL) scale and the Geriatric Depression Scale (GDS) were assessed before, after the last (fifth) session, and then followed up at 1 and 3 months. Neurophysiological evaluations included resting and active motor threshold (rMT and aMT), and the duration of transcallosal inhibition (TI) before and after the end of the treatment sessions. At base line assessment there were no significant differences between groups in any of the rating scales. The high frequency rTMS group improved significantly more than the low frequency and sham groups in all rating scales (MMSE, IADL, and GDS) and at all time points after treatment. Measures of cortical excitability immediately after the last treatment session showed that treatment with 20 Hz rTMS reduced TI duration. These results confirm that five daily sessions of high frequency rTMS over the left and then the right DLPFC improves cognitive function in patients with mild to moderate degree of AD. This improvement was maintained for 3 months. High frequency rTMS may be a useful addition to therapy for the treatment of AD.     

Effect of Two Weeks of rTMS on Brain Activity in Healthy Subjects During an n-Back Task: A Randomized Double Blind Study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has shown significant efficiency in the treatment of several psychiatric disorders. In depressive disorders, the dorsolateral prefrontal cortex (DLPFC) is the main target for rTMS, but the effects of this stimulation on cognitive functions and their neural correlates are not well known. Previous works have established that the left DLPFC is reliably activated during the n-back working memory task.ObjectiveThe aim of this randomized double-blind study was to determine the impact of rTMS applied to the DLPFC on brain activity during an n-back task in healthy subjects.MethodsAfter randomization, twenty subjects received either active treatment (10 sessions; 1 session a day; frequency = 10 Hz; intensity = 110% of motor threshold) or placebo treatment (sham coil). Subjects performed an n-back task during two functional magnetic resonance imaging sessions (one before stimulation, and one after 10 active or sham rTMS sessions).ResultsNo significant changes, neither in mood nor in performance in the n-back task, were shown. A significant group-by-time interaction effect was found in the bilateral middle frontal gyrus and in the left caudate nucleus.ConclusionsThese results show that rTMS applied on the left DLPFC had close and remote effects on brain areas involved in working memory.     

Repetitive transcranial magnetic stimulation influences mood in healthy male volunteers

The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS. In contrast the aim of this randomised sham-controlled study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and six Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”. We found a significant reduction of the BDI sum score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI sum score were caused by sham stimulation (GLM, p = 0.109). The BDI single item analyses revealed within and between group differences supporting the modifying effect of rTMS on BDI. According to the employed VAS we did not find significant differences caused by active or sham stimulation in five of six VAS. In the VAS labelled lively/gloomy the active group was found to be more “gloomy” (p = 0.0111) immediately after stimulation. Our data show that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men, whereas no significant long-term changes were found in VAS.     

Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression

There is evidence that repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has antidepressive properties. In the present study we evaluated the clinical status and the hemodynamic responses during mental work in the prefrontal cortex before therapeutic rTMS. Twelve patients diagnosed with major depression (DSM-IV) were randomized in a sham-controlled cross-over treatment protocol of 4 weeks' duration consisting of two periods of 5 days with rTMS separated by 9 days of no stimulation. rTMS (10 Hz) was applied to the left dorsolateral prefrontal cortex. Hemodynamic changes in the prefrontal cortex during mental work were evaluated by multi-site near-infrared spectroscopy (NIRS). Scores on the Hamilton Depression Rating Scale (HAMD) decreased significantly by -5.4 points after 5 days of active stimulation, whereas it did not change (+1.6 points) after sham stimulation. Absence of a task-related increase of total hemoglobin concentrations at the stimulation site (P<0.005), but not at other locations, before the first active rTMS significantly predicted the clinical response to active rTMS. Clinical benefits of rTMS are predicted by low local hemodynamic responses and support the idea of activation-dependent targeting of rTMS location.     

High (20-Hz) and low (1-Hz) frequency transcranial magnetic stimulation as adjuvant treatment in medication-resistant depression

Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have found antidepressant effects when high frequency stimulation (HF-rTMS; >1 Hz) is applied over the left prefrontal cortex (LPF). A few studies have also reported success with low frequency stimulation (LF-rTMS) to the right prefrontal cortex (RPF). Both HF-rTMS and LF-rTMS have been reported to work better in areas with cerebral hypometabolism or hypermetabolism, respectively. Thirty medication-resistant patients with major depression were randomized into three groups. The first group received sham rTMS and the second group received active rTMS (20-Hz rTMS to the LPF and 1-Hz rTMS to the RPF). The third group, however, received active rTMS that was focused on different regions of the brain after examination with single photon emission computed tomography (20-Hz rTMS to an area of relatively low activity and 1-Hz rTMS to an area showing relatively high activation). Patients and raters were blind to the treatment condition. Comparison of the sham rTMS group with the overall group that received active rTMS revealed statistically significant changes on the Hamilton Rating Scale for Depression after 10 sessions. This study demonstrated that combined 20+1-Hz rTMS was effective, but no additional advantages were obtained by focusing rTMS on areas identified by single photon emission tomography as showing high versus low levels of functional activity.     

Identifying brain imaging correlates of clinical response to repetitive transcranial magnetic stimulation (rTMS) in major depression

BackgroundPartial response and non-response to treatments are common problems in major depression. The identification of biological markers of clinical response may be of special interest for some adjunctive treatments, such as repetitive transcranial magnetic stimulation (rTMS), as it may ultimately improve their cost-effectiveness.ObjectiveTo identify pre-treatment functional imaging correlates of clinical response to rTMS in major depression.MethodsWe evaluated 21 depressed patients. They were randomized to receive 15 sessions of active or sham rTMS on the left dorsolateral prefrontal cortex. Functional magnetic resonance imaging (fMRI) was used to assess pre-treatment regional brain activity evoked by a word generation task. These regional activations were correlated (voxel-wise) with the Hamilton Rating Scale for Depression (HAM-D) reduction between baseline and end of treatment. A group of 13 healthy controls was also assessed using the same fMRI protocol to obtain reference imaging measurements.ResultsAt the end of treatment, the percentage of patients with a HAM-D reduction greater than 50% was larger in the active than in the sham rTMS group (70% vs. 27.3%). In the active rTMS group, larger HAM-D reductions were significantly correlated with smaller deactivations during pre-treatment fMRI assessment in the anterior cingulate, the left medial orbitofrontal and the right middle frontal cortices, in addition to larger activations in the left ventral-caudal putamen.ConclusionsThese results suggest that brain activity in regions arguably relevant for major depression may predict clinical response to rTMS. This approach may help in identifying the most suitable candidates to undergo rTMS treatment.     

Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study.

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.     

Fast Left Prefrontal rTMS Reduces Post-Gastric Bypass Surgery Pain: Findings From a Large-Scale,Double-Blind,Sham-Controlled Clinical Trial

BackgroundA single session of left prefrontal rTMS has been shown to have analgesic effects, and to reduce post-operative morphine use. We sought to test these findings in a larger sample, and try and see if multiple sessions had additive analgesic benefit.Methods108 patients undergoing laparoscopic gastric bypass surgery received two sessions of 10 Hz rTMS (110% of motor threshold) over the left dorsolateral prefrontal cortex (one immediately following surgery and one 4 h later). Participants were randomly assigned to receive 2 sessions of real rTMS, 2 sessions of sham, 1 real then 1 sham, or 1 sham then 1 real rTMS treatments. Patients and study staff were blind to rTMS conditions.ResultsUnlike previous rTMS trials for post-operative pain, no differences emerged between groups with respect to total patient-controlled analgesia usage (IV hydromorphone). However, despite no difference in IV analgesic usage, subjects that received 2 real rTMS sessions rated both the affective and sensory dimensions of their pain significantly lower than those in the sham–sham group at several time points during the post-surgical/post-rTMS period.ConclusionsThis study suggests that left prefrontal rTMS may produce significant analgesic effects in the perioperative setting. However, further work is needed to understand this effect and attempt to make it clinically useful in light of the lack of effect on PCA hydromorphone use.     

Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy

Objectives:  Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).
Methods:  We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.
Results:  Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 – 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks ( t =−0.22, p=0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment ( t =1.58, p=0.13). The motor threshold did not significantly change after 2 weeks of active treatment ( t =1.11, p=0.28).
Conclusions:  Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.     

Adjunctive high-frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) was not effective in obsessive–compulsive disorder but improved secondary depression

BackgroundThere is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful in obsessive–compulsive disorder (OCD) patients.MethodsOur objective was to examine efficacy of adjunctive right prefrontal high-frequency (rapid) rTMS treatment in OCD patients. 42 patients with OCD were randomly assigned to 10 sessions of add-on high-frequency right prefrontal active rTMS (10 Hz, 110% of motor threshold, 4 s per train, 20 trains per session) or sham stimulation. They were rated on Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A) and Clinical Global Impression-Severity of Illness (CGI-S) at baseline, day 14 and day 28. The dose of antiobsessive drug was kept constant throughout the period of assessment.ResultsFor YBOCS scores, repeated measures ANOVA showed significant main effect of treatment, but no effect of treatment over time (Pillai's Trace F = 1.39, p = .262). However, significant effect of treatment over time as shown by interaction effect for both HAM-D (Pillai's Trace F = 3.67, p = .035, η² = .158) and HAM-A scores (Pillai's Trace F = 5.22, p = .01, η² = .211) were seen.ConclusionAdjunctive high-frequency right prefrontal rTMS does not have any significant effect in the treatment of OCD. However, it is modestly effective in the treatment of comorbid depressive symptoms in patients with OCD.     

Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Facial Affect Recognition in Schizophrenia

ObjectiveFacial affect recognition, a basic building block of social cognition, is often impaired in schizophrenia. Poor facial affect recognition is closely related to poor functional outcome; however, neither social cognitive impairments nor functional outcome are sufficiently improved by antipsychotic drug treatment alone. Adjunctive repetitive transcranial magnetic stimulation (rTMS) has been shown to enhance cognitive functioning in both healthy individuals and in people with neuropsychiatric disorders and to ameliorate clinical symptoms in psychiatric disorders, but its effects on social cognitive impairments in schizophrenia have not yet been studied. Therefore, we evaluated the effects of sham-controlled rTMS on facial affect recognition in patients with chronic schizophrenia.MethodInpatients (N = 36) on stable antipsychotic treatment were randomly assigned to double-blind high-frequency (10 Hz) rTMS or sham stimulation for a total of ten sessions over two weeks. In the verum group, each session consisted of 10 000 stimuli (20 trains of 5 s) applied over the left dorsolateral prefrontal cortex at 110% of motor threshold. Facial affect recognition was assessed before (T0) and after (T1) the ten sessions.ResultsFacial affect recognition improved significantly more after rTMS (accuracy change: mean = 8.9%, SD = 6.0%) than after sham stimulation (mean = 1.6%, SD = 3.5; Cohen's d = 1.45). There was no correlation with clinical improvement.ConclusionOur results indicate that prefrontal 10 Hz rTMS stimulation may help to ameliorate impaired facial affect recognition in schizophrenia.