rTMS Treatment Course Research Articles

Effect of sleep quality on repetitive transcranial magnetic stimulation outcomes in depression.

While repetitive transcranial magnetic stimulation (rTMS) is effective for 50-60% of those treatment-resistant depression, it is critical to identify predictors of response for optimal patient selection to improve therapy. Insomnia is a known symptom of depression that is both correlated with depression severity and associated with poor antidepressant response. Therefore, understanding this relationship may open new opportunities for the optimization of rTMS treatment. We aimed to explore whether baseline sleep quality, specifically insomnia, is associated with rTMS outcomes in a naturalistic sample of 975 patients (age 18-90; 63.9% F) receiving a standard course of rTMS treatment from two outpatient TMS clinics located within psychiatric hospitals in the United States. One site additionally collected information on concurrent medication use on 350 patients; among these, we examined whether pharmacological treatment of insomnia affected TMS treatment response. Depression was measured using the 30-item Inventory of Depressive Symptomology Self Report (IDS-SR) in site one and an abbreviated 16-item Quick Inventory of Depressive Symptomology (QIDS) derived from the IDS-SR in site two. Sleep disturbances were measured using three insomnia-related questions. Multilevel logistic regression was used to determine whether baseline insomnia scores were associated with TMS treatment outcome. Upon dichotomous categorization of the sample by insomnia and sleep-medication use, depression and sleep scores were analyzed across time using mixed repeated measures ANOVA. We found that sleep quality improves after TMS (p<.001) and correlates with improvement in non-insomnia related depression symptoms (r= .318, p<.001). We found that among those who had significant insomnia at baseline, those not using sleep medications had significantly worse post-treatment IDS-SR scores compared to those using sleep medications (p=. 021) despite no difference in final insomnia score. Together, our results suggest that while baseline insomnia is not associated with TMS effectiveness, treating insomnia may affect the trajectory of TMS therapy. Future prospective studies are needed to examine the effect of insomnia treatment alongside TMS for depression.

Repetitive transcranial magnetic stimulation reshaped the dynamic reconfiguration of the executive and reward networks in individuals with tobacco use disorder

BackgroundStudies have demonstrated the potential of repetitive transcranial magnetic stimulation (rTMS) to decrease smoking cravings in individuals with tobacco use disorder (TUD). However, the neural features underlying the effects of rTMS treatment, especially the dynamic attributes of brain networks associated with the treatment, remain unclear. MethodsUsing dynamic functional connectivity analysis, this study first explored the differences in dynamic functional network features between 60 subjects with TUD and 64 nonsmoking healthy controls (HCs). Then, the left dorsolateral prefrontal cortex (DLPFC) was targeted for a five-day course of rTMS treatment in the 60 subjects with TUD (active rTMS in 42 subjects and sham treatment in 18 subjects). We explored the effect of rTMS on the dynamic network features associated with rTMS by comparing the actively treated group and the sham group. ResultsCompared to nonsmokers, TUD subjects exhibited an increased integration coefficient between the frontoparietal network (FPN) and the basal ganglia network (BGN) and a reduced integration coefficient between the medial frontal network (MFN) and the FPN. Analysis of variance revealed that rTMS treatment reduced the integration coefficient between the FPN and BGN and improved the recruitment coefficient of the FPN. LimitationsThis study involved a limited sample of young male smokers, and the findings may not generalize to older smokers or female smokers with an extensive history of smoking. ConclusionrTMS treatment of the left DLPFC exhibited significant effectiveness in restructuring the neural circuits associated with TUD while significantly mitigating smoking cravings.

Depressive symptom trajectories with prolonged rTMS treatment

BackgroundA prolonged repetitive transcranial magnetic stimulation (rTMS) treatment course could be beneficial for some patients experiencing major depressive episodes (MDE). We identified trajectories of rTMS response in depressive patients who received an extended rTMS treatment course and sought to determine which trajectories achieved the greatest benefit with a prolonged treatment course. MethodWe applied group-based trajectory modeling to a naturalistic dataset of depressive patients receiving a prolonged course of sequential bilateral rTMS (up to 51 treatment sessions) to the dorsolateral prefrontal cortex. Trajectories of the PHQ-9 with extended treatment courses were characterized, and we explored the association between baseline clinical characteristics and group membership using multinomial logistic regression. ResultsAmong the 324 study participants, four trajectories were identified: “linear response, extended course” (N = 73; 22.5 %); “nonresponse” (N = 23; 7.1 %); “slowed response” (N = 159; 49.1 %); “rapid response, standard treatment length” (N = 69; 21.3 %). Only the “linear response, extended course” group showed considerable clinical improvement after receiving additional rTMS treatments. Greater baseline depressive symptoms were associated with linear response and non-response. ConclusionOur results confirmed the distinctive response trajectories in depressive patients receiving rTMS and further highlighted that prolonged rTMS treatment courses may be beneficial for a subset of patients with higher initial symptom levels and linear early treatment response.

Clinical Practice Guidelines for the Therapeutic Use of Repetitive Transcranial Magnetic Stimulation in Neuropsychiatric Disorders.

Clinical Practice Guidelines for the Therapeutic Use of Repetitive Transcranial Magnetic Stimulation in Neuropsychiatric Disorders.

Extension of transcranial magnetic stimulation treatment for depression in non-responders: Results of a naturalistic study

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) shows efficacy in the treatment of major depressive disorder using a standard course of 20–36 treatment sessions. However, research efforts are being made to improve overall response and remission rates. Evidence from open-label extension studies of randomized control trials suggests that extending the rTMS treatment course beyond 36 treatments may improve outcomes, however, little has been published on the benefit of extended TMS treatment courses in clinical practice. ObjectiveIn this retrospective naturalistic observational study, we studied response rates on continuation of rTMS following failure of the first round of 36 treatments. MethodsFrom 142 patients who received conventional rTMS and 29 who underwent theta-burst stimulation (TBS) at Massachusetts General Hospital TMS clinical service, 28 non-responders (23 to rTMS and 5 to TBS) opted to continue their treatment beyond session 36. The treatment protocol allowed personalization in target, TMS protocol, as well as number of pulses and sessions as clinically indicated. Sustained response and remission using Hamilton Rating Scale for Depression, 17-items (HAMD-17) was the primary outcome. ResultsThe average number of overall treatment sessions was 70.54 ± 16.73 for the sample. Overall, there was a 53.57% response rate and a 32.14% remission rate. Response and remission rates rose as the number of sessions increased and there did not appear to be a plateau in response over time. ConclusionOur results support the idea that subpopulation of TMS patients are late responders. Continuation of TMS up to 72 treatments among those patients who do not meet response criteria by session 36 may improve overall response rates. While the number of subjects and study design limit generalization, given the fact that these patients were medication refractory and had failed initial course of TMS, the result of this study is encouraging.

Cold Cognition as Predictor of Treatment Response to rTMS; A Retrospective Study on Patients With Unipolar and Bipolar Depression

BackgroundCognitive impairments are prevalent in patients with unipolar and bipolar depressive disorder (UDD and BDD, respectively). Considering the fact assessing cognitive functions is increasingly feasible for clinicians and researchers, targeting these problems in treatment and using them at baseline as predictors of response to treatment can be very informative.MethodIn a naturalistic, retrospective study, data from 120 patients (Mean age: 33.58) with UDD (n = 56) and BDD (n = 64) were analyzed. Patients received 20 sessions of bilateral rTMS (10 Hz over LDLPFC and 1 HZ over RDLPFC) and were assessed regarding their depressive symptoms, sustained attention, working memory, and executive functions, using the Beck Depression Inventory (BDI-II) and Neuropsychological Test Automated Battery Cambridge, at baseline and after the end of rTMS treatment course. Generalized estimating equations (GEE) and logistic regression were used as the main statistical methods to test the hypotheses.ResultsFifty-three percentage of all patients (n = 64) responded to treatment. In particular, 53.1% of UDD patients (n = 34) and 46.9% of BDD patients (n = 30) responded to treatment. Bilateral rTMS improved all cognitive functions (attention, working memory, and executive function) except for visual memory and resulted in more modulations in the working memory of UDD compared to BDD patients. More improvements in working memory were observed in responded patients and visual memory, age, and sex were determined as treatment response predictors. Working memory, visual memory, and age were identified as treatment response predictors in BDD and UDD patients, respectively.ConclusionBilateral rTMS improved cold cognition and depressive symptoms in UDD and BDD patients, possibly by altering cognitive control mechanisms (top-down), and processing negative emotional bias.

Treatment of anxiety symptoms in patients receiving rTMS for treatment resistant depression

This retrospective analysis examined the effects of left-sided dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on comorbid anxiety symptoms patients with treatment resistant depression (TRD). Response rates, remission rates, reliable change index (RCI), and clinically significant change (CSC) were assessed using the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety subscale at over an average of 32.9 treatments ( SD ​= ​9.2). Fifty-seven TRD patients showed statistically and clinically significant improvement in all anxiety measurements with left DLPFC rTMS. This retrospective study had no sham control and allowed for medication changes during the rTMS treatment course. Left DLPFC rTMS may be an important tool in reducing anxiety in TRD patients, improving overall treatment resistant symptoms and suicide risk. • Anxious depression is associated with more suicide risk and treatment resistance. • Transcranial Magnetic Stimulation (TMS) may be a treatment option. • TMS improved anxiety in patients with treatment resistant depression and anxiety.

Absence of early mood improvement as a robust predictor of rTMS nonresponse in major depressive disorder.

Symptoms of major depressive disorder (MDD) are reported to change early in treatment with repetitive transcranial magnetic stimulation (rTMS). We evaluated early changes in sleep, anxiety, and mood as predictors of nonresponse to rTMS treatment. Three hundred twenty-nine subjects with nonpsychotic MDD completed a 6-week course of rTMS treatment. Subjects were stratified by the severity of their baseline depression, and had their overall depressive symptoms recorded every week of treatment. We evaluated lack of improvement in sleep, anxiety, and mood symptoms after 1 and 2 weeks as potential predictors of eventual nonresponse, defined as <50% improvement in compositive depressive symptoms after 6 weeks. This was measured as negative predictive value (NPV; the likelihood that lack of early symptom improvement accurately predicted eventual treatment nonresponse). Subjects with severe or very severe baseline depression achieving <20% improvement in mood at 1 week were correctly predicted as nonresponders with NPVs largely >90%. At 2 weeks, subjects with very severe baseline depression who failed to demonstrate any improvement in mood were all nonresponders. Lack of improvement in sleep at 2 weeks was also a significant predictor. Identifying a lack of early mood improvement is a practical and robust method to predict rTMS nonresponse. This suggests a treatment protocol change may be indicated in patients with more severe baseline depression showing minimal early mood improvement.

Predictors of clinical response after rTMS treatment of patients suffering from drug-resistant depression

Repeated transcranial magnetic stimulation (rTMS) is a therapeutic brain-stimulation technique that is particularly used for drug-resistant depressive disorders. European recommendations mention the effectiveness of 30 to 64%. The failure rate of treatment is high and clinical improvement is visible only after a certain period of time. It would thus be useful to have indicators that could anticipate the success of treatment and more effectively guide therapeutic choices. We aimed to find predictive indicators of clinical improvement at 1 month after the start of rTMS treatment among the data collected during the care of patients with drug-resistant depression included in the Neuromodulation Unit of the Esquirol Hospital in Limoges since 2007. In total, 290 patients with a pharmaco-resistant depressive episode, according to the Hamilton Depression Rating Scale (HDRS) (score ≥8), before treatment who underwent a complete course of rTMS treatment and did not object to the use of their collected data were included. The clinical response in routine practice, corresponding to a decrease in the HDRS score of at least 50% from inclusion, was determined and complemented by interquartile analysis. A combination of factors predictive of clinical response during care, such as a short duration of the current depressive episode associated with a higher HDRS agitation item value (or a lower perceived sleepiness value) and a higher number of previous rTMS treatments, were identified as being useful in predicting the efficacy of rTMS treatment in routine clinical practice, thus facilitating the therapeutic choice for patients with drug-resistant depression.

Modulation of Dorsolateral Prefrontal Cortex Glutamate/Glutamine Levels Following Repetitive Transcranial Magnetic Stimulation in Young Adults With Autism.

Altered excitatory and inhibitory neurotransmission has been implicated in autism spectrum disorder (ASD). Interventions using repetitive transcranial magnetic stimulation (rTMS) to enhance or inhibit cortical excitability are under study for various targets, though the mechanistic effects of rTMS have yet to be examined in ASD. Here, we examined whether an excitatory rTMS treatment course modulates glutamatergic (Glx) or γ-aminobutyric acid (GABA) metabolite levels in emerging adults with ASD. Twenty-eight participants with ASD and executive function impairment [23.3 ± 4.69 years; seven-female] underwent two magnetic resonance spectroscopy (MRS) scans of the left dorsolateral prefrontal cortex (DLPFC). MRS scans were acquired before and after participants with ASD were randomized to receive a 20-session course of active or sham rTMS to the DLPFC. Baseline MRS data was available for 19 typically developing controls [23.8 ± 4.47 years; six-female]. Metabolite levels for Glx and GABA+ were compared between ASD and control groups, at baseline, and metabolite level change, pre-to-post-rTMS treatment, was compared in ASD participants that underwent active vs. sham rTMS. Absolute change in Glx was greater in the active vs. sham-rTMS group [F(1,19) = 6.54, p = 0.02], though the absolute change in GABA+ did not differ between groups. We also examined how baseline metabolite levels related to pre/post-rTMS metabolite level change, in the active vs. sham groups. rTMS group moderated the relation between baseline Glx and pre-to-post-rTMS Glx change, such that baseline Glx predicted Glx change in the active-rTMS group only [b = 1.52, SE = 0.32, t(18) = 4.74, p < 0.001]; Glx levels increased when baseline levels were lower, and decreased when baseline levels were higher. Our results indicate that an interventional course of excitatory rTMS to the DLPFC may modulate local Glx levels in emerging adults with ASD, and align with prior reports of glutamatergic alterations following rTMS. Interventional studies that track glutamatergic markers may provide mechanistic insights into the therapeutic potential of rTMS in ASD.Clinical Trial Registration: Clinicaltrials.gov (ID: NCT02311751), https://clinicaltrials.gov/ct2/show/NCT02311751?term=ameis&rank=1; NCT02311751.

Day-to-day variability in motor threshold during rTMS treatment for depression: Clinical implications

BackgroundWhen repetitive transcranial magnetic stimulation (rTMS) is used to treat medication refractory depression, the treatment pulse intensity is individualized according to motor threshold (MT). This measure is often acquired only on the first day of treatment, as per the protocol currently approved by Food and Drug Administration. ObjectiveHere, we aimed to assess daily MT variability across an rTMS treatment course and simulate the effects of different schedules of MT assessment on treatment intensity. MethodsWe conducted a naturalistic retrospective study with 374 patients from a therapeutic rTMS program for depression that measures MT daily. ResultsFor each patient, in almost half the TMS sessions, MT varied on average more than 5% as compared to the baseline MT acquired in the first treatment day. Such variability was only minimally impacted by having different TMS technicians acquiring MT in different days. In a smaller cohort of healthy individuals, we confirmed that the motor hotspot localization method, a critical step for accurate MT assessment, was stable in different days, arguing that daily MT variability reflects physiological variability, rather than an artifact of measurement error. Finally, in simulations of the effect of one-time MT measurement, we found that half of sessions would have been 5% or more above or below target intensity, with almost 5% of sessions 25% above target intensity. The simulated effects of weekly MT measurements were significantly improved. ConclusionsIn conclusion, MT varies significantly across days, not fully dependent on methods of MT acquisition. This finding may have important implications for therapeutic rTMS practice regarding safety and suggests that regular MT assessments, daily or at least weekly, would ameliorate the effect.

Comparing theta burst stimulation with standard left high frequency transcranial magnetic stimulation in the treatment of depression in a randomized controlled study: A preliminary comparison study

Abstract Background Theta Burst stimulation (TBS) is a promising alternative to standard repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD). TBS treatment is delivered over a much shorter time than rTMS, enabling more patients to be treated with the same resources. The aim of this preliminary study was to explore the efficacy of an intensive bilateral TBS protocol (BL TBS) compared to a standard rTMS protocol. Methods Thirty-two outpatients with TRD were randomized to a standard rTMS protocol and 34 outpatients were randomized to a TBS protocol. Treatment was delivered over two week or four weeks. Both treatment groups received twenty treatments in total. Patients were assessed at baseline, week 1, week 2 and week 4. Results There were no major differences in baseline depression severity between the randomized treatment groups. There was no significant difference in response and remission rates between the two groups. In the standard rTMS group, 40.6% met criteria for response and 25% met criteria for remission. These rates were 20.6% and 25.5% respectively for the TBS group. There was a significant reduction in mean depression scores for both treatment groups (p Limitations This was not a sham-controlled study, so placebo response rates are not known. Conclusion TBS provided clinical benefit, which on most outcome measures did not differ significantly from outcomes with a standard course of rTMS treatment, and could be advantageous from a clinical, service and patient perspective.

The changes in kynurenine metabolites induced by rTMS in treatment-resistant depression: A pilot study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that is considered a valuable and promising technique for improving depressive symptoms in treatment-resistant depression (TRD). However, the exact mechanism by which rTMS ameliorates depressive symptoms remains to be clarified. ObjectiveThe aim of the present study was to analyzed the changes in metabolites of patients with TRD in the rTMS treatment, especially focusing on the kynurenine (KYN) pathway. MethodsThirteen participants with TRD were enrolled in a high-frequency (10 Hz) rTMS study. Cognitive function, depressive symptoms and the concentration of plasma tryptophan (TRP) metabolites were measured at baseline and at the endpoint of rTMS treatment. ResultsrTMS treatment significantly improved depressive symptom scores and some subscales of cognitive dysfunction. The present study has demonstrated that rTMS treatment significantly increased plasma TRP levels and significantly decreased plasma serotonin levels, while plasma KYN and kynurenic acid level as well as KYN/TRP ratio remained unchanged. ConclusionsThis is the first metabolomic study of patients with TRD undergoing rTMS treatment. To validate the present results, it is necessary to increase the number of cases including controls, use a sample of cerebrospinal fluid, and measure blood concentration over time in the course of rTMS treatment.

The effects of extended rTMS treatment course on response outcome in patients with Major Depressive Disorder - Salience 51

Background: A naturalistic study was conducted to assess the effects of 15 additional rTMS treatments on patients (i.e., Salience 51 patients) diagnosed with Major Depressive Disorder (MDD) who failed to achieve and maintain remission (≥70% improvement from baseline PHQ-9 score) for two consecutive weeks, after an acute course of rTMS (36 treatments) ((ntotal = 90), nmales =3 1, Mage = 43.8 years, SD = 18.84). Treatment effects were measured using the PHQ-9, GAD-7, CHRT, QIDS, and Zung self-rater scales. Methods: Salience 51 patients received 15 additional rTMS treatments after their acute course of 36 treatments. Treatments were administered over the right (1 Hz, 360 pulses) and left (20 Hz, 1200 pulses) dorsolateral prefrontal cortex (dlPFC) at 120% motor threshold, five times a week for approximately eight weeks. Assessments were completed before treatment, at weekly intervals, at treatment 36, and at the end of the treatment. Results: Response rate (≥ 50% improvement on PHQ-9) increased from 45.56% of patients at treatment 36 to 62.22% of patients after 51 treatments. Analysis of variance showed a main effect of additional 15 treatments on treatment response outcome at start, treatment 36, and end PHQ9 [F(2, 267) = 82.02, p < .001, ƞ2p = 0.38]. A Bonferroni post-hoc comparison indicates that the initial mean PHQ-9 score (M = 15.9, SD = 23.08) was significantly different than at treatment 36 (M = 9.03, SD = 20.28). Even greater mean difference of -8.31 was found between initial and ending mean PHQ-9 (M = 7.59, SD = 21.55) scores. Conclusions: The findings support the need for an individualized number of rTMS treatments to reach maximized potential treatment response, as 46% of Salience 51 patients reported a continued decrease of depressive symptoms after treatment 36. Funding: Patients who were already seeking TMS treatment were financially responsible for their acute courses of TMS Therapy. The acute course may have been covered by insurance and/or privately paid for by the patient. If the patients qualified for the study, they were given the option to participate in the study. They received 15 additional TMS treatments provided by our company, a private clinical practice, at no cost to the patient and they were under no obligation to participate or finish the study.

Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Depression: Experience From a Clinical Setting.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive Food and Drug Administration (FDA)-approved treatment for unipolar treatment-resistant depression (TRD). rTMS has been utilized clinically to treat bipolar TRD; however, there remains a lack of evidence and support for effectively utilizing this intervention for bipolar TRD. We retrospectively analyzed data from a group of patients who were treated with rTMS for unipolar or bipolar TRD and describe a case example to further delineate management techniques for employing rTMS in the treatment of bipolar TRD. Records of 71 patients treated with rTMS for unipolar (n=54) or bipolar (n=17) TRD between 2008 and 2017 were reviewed. The primary outcome of depression severity, the Quick Inventory of Depressive Symptomatology, was completed at baseline and after every 5 sessions throughout the course of 30 treatments. Secondary outcomes involved a comparison of outcomes and clinical characteristics within and between the bipolar and unipolar TRD groups. In the total sample, patients' depression improved significantly over the course of treatment. Patients with bipolar TRD showed greater response and remission rates over the course of treatment compared with patients with unipolar TRD, but this difference was not statistically significant. Both groups showed a similar pattern of depression response over treatment time. No manic or hypomanic episodes occurred during any patient's course of rTMS treatment. A case example is provided discussing the timing of rTMS in a patient with bipolar depression to decrease the likelihood of treatment-induced hypomania. Limitations included the small overall sample size, the smaller size of the patient group with bipolar TRD compared with the group with unipolar TRD, and the naturalistic setting of this study. Our data suggest that rTMS may be equally effective and safe for patients with both unipolar and bipolar depression. Patients with bipolar TRD showed a similar response profile over treatment time compared with patients with unipolar TRD.

High-Frequency Repetitive Transcranial Magnetic Stimulation Applied to the Parietal Cortex for Low-Functioning Children With Autism Spectrum Disorder: A Case Series

Background: Repetitive transcranial magnetic stimulation (rTMS) is a safe and efficacious technique to stimulate specific areas of cortical dysfunction in several neuropsychiatric diseases; however, it is not known whether high-frequency rTMS (HF-rTMS) over the left inferior parietal lobule, in low functioning children with autism spectrum disorder (ASD), improves core symptoms. Method: Eleven low-functioning children with ASD completed two separate HF-rTMS treatment courses, 6 weeks apart. Each treatment course involved five 5-s trains at 20 Hz, with 10-min inter-train intervals, on left inferior parietal lobule each consecutive weekday for a 3-week period (15 treatments per course). Subjects were assessed at five time points: immediately before and after the first HF-rTMS course, immediately before and after the second HF-rTMS course, and 6 weeks after the second rTMS treatment course. Treatment effectiveness was evaluated using the Verbal Behavior Assessment Scale (VerBAS) and Autism Treatment Evaluation Checklist (ATEC). The latter test consists of four subtest scales: Language, Sociability, Sensory, and Behavior. In addition, daily treatment logbooks completed by parents were considered as one of the outcome measures. Results: Participants showed a significant reduction in language- and social-related symptoms measured by ATEC from pretreatment to the 6-week follow-up after the second treatment course. Moreover, some possible improvements in imitation and cognition were reported by caregivers. Conclusions: Our findings suggest that HF-rTMS over the left parietal cortex might improve core deficits in low-functioning children with ASD.

Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder.

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS.MethodsMedications were tabulated for 181 MDD patients who underwent a six‐week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left‐sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS‐SR30) total score after 2, 4, and 6 weeks.ResultsUse of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non‐users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non‐users (39.2% vs. 22.0%, p = 0.02).ConclusionsConcomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis‐based treatment studies will aid in determining causal relationships between medication treatments and outcome.

Repetitive Transcranial Magnetic Stimulation for Treatment of Depression in a Patient With Severe Traumatic Brain Injury

Traumatic brain injury (TBI) commonly presents with a constellation of findings, including physical, cognitive, and psychological disturbances. Traditionally, few options have been available for long-term management of mood symptoms for post-TBI patients who are refractory to medications. Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative treatment. A 37-year-old male with history of anxiety and bipolar depression incurred a TBI after a 60-foot fall. After his physical recovery, the patient had refractory depression. Eight months after the TBI event, he underwent a 6-week course of rTMS treatment and had a 70.8% improvement in mood symptoms by the end of the therapy as indicated by the Patient Health Questionnaire-9, transitioning from severe to mild depression according to the scoring system. Clinical correlation during the months following conclusion of rTMS therapy showed no signs of remission or adverse side effects. The patient remains stable and lives independently 1 year after treatment with mood-stabilizing medications. This case provides evidence for successful treatment of refractory depressive symptoms after severe TBI with the addition of rTMS to psychotherapy and mood-stabilizing medications, supporting the safety and tolerability of this novel therapeutic approach. Further studies are needed to validate the contribution of rTMS for management of mood symptoms in patients with TBI.

Does Therapeutic Repetitive Transcranial Magnetic Stimulation Cause Cognitive Enhancing Effects in Patients with Neuropsychiatric Conditions? A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a therapeutic intervention for neuropsychiatric illnesses and has demonstrated efficacy for treatment of major depression. However, an unresolved question is whether a course of rTMS treatment results in effects on cognitive functioning. In this systematic review and meta-analysis we aimed to quantitatively determine whether a course of rTMS has cognitive enhancing effects. We examined cognitive outcomes from randomised, sham-controlled studies conducted in patients with neuropsychiatric conditions where rTMS was administered to the dorsolateral prefrontal cortex (DLPFC) across repeated sessions, searched from PubMed/MEDLINE and other databases up until October 2015. Thirty studies met our inclusion criteria. Cognitive outcomes were pooled and examined across the following domains: Global cognitive function, executive function, attention, working memory, processing speed, visual memory, verbal memory and visuospatial ability. Active rTMS treatment was unassociated with generalised gains across the majority of domains of cognitive functioning examined. Secondary analyses revealed a moderate sized positive effect for improved working memory in a small number of studies in patients with schizophrenia (k=3, g=0.507, 95% CI=[0.183-0.831], p<.01). Therapeutic rTMS when administered to the DLPFC in patients with neuropsychiatric conditions does not result in robust cognitive enhancing effects.

A STUDY OF THE PATTERN OF RESPONSE TO rTMS TREATMENT IN DEPRESSION.

Considerable research has demonstrated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment in patients with depression. However, limited research has described the pattern of response to rTMS treatment or explored possible predictors of the likelihood of treatment response. Data from 11 clinical trials (n = 1,132) was pooled and we described the pattern of response to rTMS, rate of response, and remission as well as potential clinical and demographic predictors of response. There was a bimodal pattern of response to rTMS with the response-associated peak at 57% reduction in depression rating scale scores. About 46% of patients achieved response criteria, with 31% completing rTMS treatment in remission. A greater likelihood of response was seen for patients who had less severe depression at baseline, a shorter duration of the current episode, and recurrent rather than single episode of depression. Greater response was also seen in patients treated at higher stimulation intensity. A meaningful percentage (>40%) of patients respond to a course of rTMS treatment. Response does vary with a number of clinical and demographic variables but none of these variables exert a sufficiently strong influence on response rates to warrant using these criteria to exclude patients from treatment.