The effect of older age on outcomes of rTMS treatment for treatment-resistant depression.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16-100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%-57%/25%-33%; <60: 32%-49%/18%-25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

Sequential Multilocus Repetitive Transcranial Magnetic Stimulation for Treatment of Tinnitus With and Without Comorbid Major Depressive Disorder.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for tinnitus, although outcomes are highly variable. We previously described a multilocus sequential rTMS treatment protocol for tinnitus involving stimulation of both prefrontal and auditory targets. In this study, we report results using this approach in an open-label treatment study of tinnitus with and without comorbid major depressive disorder (MDD). MATERIALS AND METHODS: Forty patients with chronic tinnitus (mean age 56 years, ten female) and with (n = 17) or without (n = 23) MDD received multilocus rTMS administered sequentially to 1) left dorsolateral prefrontal cortex, followed by 2) auditory cortex (Heschel's gyrus). Patients completed weekly self-report ratings using the Tinnitus Functional Index (TFI) and Tinnitus Handicap Inventory, and patients with MDD completed the Inventory of Depressive Symptomatology Self-Report 30-item. RESULTS: Patients showed significant mean improvement in tinnitus at sessions 5 (mean TFI improvement 6.8 points ± 12.2, p = 0.002) and 10 (mean improvement 9.2 points ± 14.1, p = 0.002), with 48% of patients responding within ten treatment sessions. Responders were significantly older than nonresponders (61.5 ± 15 years vs 51.3 ± 16 years), and there was a trend toward decreased likelihood of response in subjects with comorbid MDD compared with subjects without comorbidity (odds ratio = 0.28, p = 0.06). Patients with comorbid MDD reported significantly less improvement after ten sessions than did those with tinnitus alone (4.3 ± 10.3 vs 14.7 ± 15.0 points, p = 0.04). Post hoc analyses suggested that the comorbid group achieved improvement comparable to that of the tinnitus-only group after 30 treatments. CONCLUSIONS: Patients showed significant improvement in tinnitus from multilocus sequential rTMS treatment, and those with tinnitus alone improved more quickly. Those with depression who continued rTMS through a full 30-session course further improved, indicating that tinnitus with comorbid MDD may respond with extended treatment.

A comparison of self- and observer-rated scales for detecting clinical improvement during repetitive transcranial stimulation (rTMS) treatment of depression.

Clinical outcomes of repetitive Transcranial Magnetic Stimulation (rTMS) for treatment of Major Depressive Disorder (MDD) vary widely, and no single mood rating scale is standard for assessing rTMS outcomes. This study of 708 subjects undergoing clinical rTMS compared the performance of four scales in measuring symptom change during rTMS treatment. Self-report and observer ratings were examined weekly with the Inventory of Depressive Symptomatology 30-item (IDS), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item (POMS), and Hamilton Depression Rating Scale 17-item (HDRS). While all scales were correlated and detected significant improvement, the degree of improvement over time as well as response (33-50%) and remission (20-24%) rates varied significantly. Higher baseline severity was associated with lower likelihood of remission, and greater improvement by sessions 5 and 10 predicted response across all scales. Use of only a single scale to assess outcome conferred 14-36% risk of failing to detect response/remission indicated by another scale. The PHQ was most likely to indicate improvement and least likely to miss response or remission. These findings indicate that assessment of symptom burden during rTMS treatment may be most accurately assessed through use of multiple instruments.

Bilateral Cerebellar Repetitive Transcranial Magnetic Stimulation for Chronic Ataxia After Hemorrhagic Stroke: a Case Report.

There are insufficient treatment options available for recovery related to cerebellar ataxia. Limited data using repetitive transcranial magnetic stimulation (rTMS) have demonstrated reduction of symptom burden, though associated with nonuniform cerebellar ataxia etiologies and differing rTMS treatment protocols. Additionally, there are limited available data for use of rTMS in individuals suffering from stroke-related symptoms. We present the case of a patient with chronic cerebellar ataxia following a hemorrhagic stroke who underwent inhibitory rTMS to bilateral cerebellar targets with demonstrated improvement in symptoms.

Pretreatment pupillary reactivity is associated with differential early response to 10 Hz and intermittent theta-burst repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD).

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD). Two common rTMS protocols, 10 Hz and intermittent theta burst stimulation (iTBS), have comparable rates of efficacy in groups of patients. Recent evidence suggests that some individuals may be more likely to benefit from one form of stimulation than the other. The pretreatment pupillary light reflex (PLR) is significantly associated with response to a full course of rTMS using heterogeneous stimulation protocols. OBJECTIVE: To test whether the relationship between pretreatment PLR and early symptom improvement differed between subjects treated with iTBS or 10 Hz stimulation. METHODS: PLR was measured in 52 subjects who received solely 10 Hz (n = 35) or iTBS (n = 17) to left dorsolateral prefrontal cortex (DLPFC) for the first ten sessions of their treatment course. Primary outcome measure was the percent change of Inventory of Depressive Symptomatology - Self Report (IDS-SR) from session 1 to session 10. RESULTS: There was a positive association between normalized maximum constriction velocity (nMCV) and early improvement in subjects receiving 10 Hz stimulation (R = 0.48, p = 0.004) and a negative association in subjects receiving iTBS (R = -0.52, p = 0.03). ANOVA revealed a significant interaction between nMCV and the type of initial stimulation (p = 0.001). Among subjects with low nMCV, those initially treated with iTBS showed 2.6 times greater improvement after 10 sessions (p = 0.01) than subjects initially receiving 10 Hz stimulation. CONCLUSION: nMCV may detect physiologic differences between those likely to benefit from 10 Hz or iTBS treatment. Future studies should examine whether PLR could guide prospective treatment selection.

Rumination symptoms in treatment-resistant major depressive disorder, and outcomes of repetitive Transcranial Magnetic Stimulation (rTMS) treatment.

Rumination is a maladaptive style of regulating thoughts and emotions. It is a common symptom of Major Depressive Disorder (MDD), and more severe rumination is associated with poorer medication and psychotherapy treatment outcomes, particularly among women. It is unclear to what extent rumination may influence the outcomes of, or be responsive to, repetitive Transcranial Magnetic Stimulation (rTMS) treatment of MDD. We retrospectively examined data collected during rTMS treatment of 155 patients (age 42.52 ± 14.22, 79 female) with moderately severe treatment-resistant MDD. The severity of rumination and depression was assessed before and during a course of 30 sessions of measurement-based rTMS treatment using the Ruminative Responses Scale (RSS) and the Patient Health Questionnaire (PHQ-9), respectively. Relationships among baseline levels of rumination, depression, and treatment outcome were assessed using a series of repeated measures linear mixed effects models. Both depression and rumination symptoms significantly improved after treatment, but improvement in depression was not a significant mediator of rumination improvement. Higher baseline rumination (but not depression severity) was associated with poorer depression outcomes independently of depression severity. Female gender was a significant predictor of worse outcomes for all RRS subscales. Both depressive and ruminative symptoms in MDD improved following rTMS treatment. These improvements were correlated, but improvement in rumination was not fully explained by reduction in depressive symptoms. These findings suggest that while improvement in rumination and depression severity during rTMS treatment are correlated, they are partly independent processes. Future studies should examine whether rumination symptoms should be specifically targeted with different rTMS treatment parameters.

Pretreatment pupillary reactivity is associated with outcome of Repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD).

BACKGROUND: Pre-treatment biomarkers for outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD) have proven elusive. One promising family of biomarkers involves the autonomic nervous system (ANS), which is dysregulated in individuals with MDD. METHODS: We examined the relationship between the pre-treatment pupillary light reflex (PLR) and rTMS outcome in 51 MDD patients. Outcome was measured as the percent change in the 30-item Inventory of Depressive Symptomatology Self Rated (IDS-SR) score from baseline to treatment 30. RESULTS: Patients showed significant improvement with rTMS treatment. There was a significant correlation between baseline pupillary Constriction Amplitude (CA) and clinical improvement over the treatment course (R = 0.41, p = 0.003). LIMITATIONS: We examined a limited number of subjects who received heterogeneous treatment protocols. Almost all patients in the study received psychotropic medications concomitant with rTMS treatment. CONCLUSION: PLR measured before treatment may be a predictive biomarker for clinical improvement from rTMS in subjects with MDD.

Repetitive transcranial magnetic stimulation treatment of major depressive disorder and comorbid chronic pain: response rates and neurophysiologic biomarkers.

BACKGROUND: Major depressive disorder (MDD) and chronic pain are highly comorbid, and pain symptoms are associated with a poorer response to antidepressant medication treatment. It is unclear whether comorbid pain also is associated with a poorer response to treatment with repetitive transcranial magnetic stimulation (rTMS). METHODS: 162 MDD subjects received 30 sessions of 10 Hz rTMS treatment administered to the left dorsolateral prefrontal cortex (DLPFC) with depression and pain symptoms measured before and after treatment. For a subset of 96 patients, a resting-state electroencephalogram (EEG) was recorded at baseline. Clinical outcome was compared between subjects with and without comorbid pain, and the relationships among outcome, pain severity, individual peak alpha frequency (PAF), and PAF phase-coherence in the EEG were examined. RESULTS: 64.8% of all subjects reported pain, and both depressive and pain symptoms were significantly reduced after rTMS treatment, irrespective of age or gender. Patients with severe pain were 27% less likely to respond to MDD treatment than pain-free individuals. PAF was positively associated with pain severity. PAF phase-coherence in the somatosensory and default mode networks was significantly lower for MDD subjects with pain who failed to respond to MDD treatment. CONCLUSIONS: Pain symptoms improved after rTMS to left DLPFC in MDD irrespective of age or gender, although the presence of chronic pain symptoms reduced the likelihood of treatment response. Individual PAF and baseline phase-coherence in the sensorimotor and midline regions may represent predictors of rTMS treatment outcome in comorbid pain and MDD.

Use of right orbitofrontal repetitive transcranial magnetic stimulation (rTMS) augmentation for treatment-refractory obsessive-compulsive disorder with comorbid major depressive disorder.

We examined the safety and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) of the right orbitofrontal cortex (OFC) in patients with refractory obsessive-compulsive disorder (OCD) and comorbid Major Depressive Disorder. All participants (n = 26) received excitatory stimulation of the left dorsolateral prefrontal cortex followed by inhibitory stimulation of bilateral supplementary motor area for 10 sessions. In 18 patients with poor early OCD response, treatment was augmented with OFC inhibitory stimulation after the tenth treatment session. Augmentation with OFC stimulation was well-tolerated, and associated with further alleviation of both OCD and depression symptoms, particularly in individuals with more severe illnesses.

Sequential Prefrontal and Temporoparietal Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment of Tinnitus With and Without Comorbid Depression: A Case Series and Systematic Review.

Background: Tinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone. Materials and Methods: Ten subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature. Results: Subjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1-12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90-180 days). Conclusions: Sequential rTMS approaches for the treatment of tinnitus-particularly those administering low-frequency treatment at left DLPFC-merit further investigation.

Psychostimulant use and clinical outcome of repetitive transcranial magnetic stimulation treatment of major depressive disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD). Psychostimulant medication use may be associated with improved rTMS outcomes, but a detailed understanding of these relationships is lacking. METHODS: We compared MDD subjects taking psychostimulants (n = 37) with those not taking one of these medications (n = 53) during a course of 30 rTMS treatments. Changes in the 30-item Inventory of Depressive Symptomatology Self Report (IDS-SR30) subscale scores were examined at treatment 30. We also subdivided subjects into three categories based on drug mechanism and looked at IDS-SR30 total score after treatments 10, 20, and 30. RESULTS: Subjects taking psychostimulants had a significantly greater overall clinical improvement than those not taking these medications at treatment 30. The psychostimulant group also improved significantly more than the control group in "sleep" and "mood/cognition," but not "anxiety/arousal" IDS-SR30 subscales. No differences were detected among individual drug categories, which may reflect the limited sample size for individual medications. There was a negative dose-response relationship for the lisdexamfetamine/dextroamphetamine group, in which lower doses were associated with better clinical outcome. CONCLUSIONS: Psychostimulant medications may enhance clinical efficacy of rTMS for MDD by preferentially impacting specific symptom domains. For some psychostimulants, these effects may be dose-dependent. Prospective clinical trials are needed to guide psychostimulant augmentation of brain stimulation therapies.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Novel method for identification of individualized resonant frequencies for treatment of Major Depressive Disorder (MDD) using repetitive Transcranial Magnetic Stimulation (rTMS): A proof-of-concept study.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD), but therapeutic benefit is highly variable. Clinical improvement is related to changes in brain circuits, which have preferred resonant frequencies (RFs) and vary across individuals. OBJECTIVE: We developed a novel rTMS-electroencephalography (rTMS-EEG) interrogation paradigm to identify RFs using the association of power/connectivity measures with symptom severity and treatment outcome. METHODS: 35 subjects underwent rTMS interrogation at 71 frequencies ranging from 3 to 17 Hz administered to left dorsolateral prefrontal cortex (DLPFC). rTMS-EEG was used to assess resonance in oscillatory power/connectivity changes (phase coherence [PC], envelope correlation [EC], and spectral correlation coefficient [SCC]) after each frequency. Multiple regression was used to detect relationships between 10 Hz resonance and baseline symptoms as well as clinical improvement after 10 sessions of 10 Hz rTMS treatment. RESULTS: Baseline symptom severity was significantly associated with SCC resonance in left sensorimotor (SM; p < 0.0004), PC resonance in fronto-parietal (p = 0.001), and EC resonance in centro-posterior channels (p = 0.002). Subjects significantly improved with 10 sessions of rTMS treatment. Only decreased SCC SM resonance was significantly associated with clinical improvement (r = 0.35, p = 0.04). Subjects for whom 10 Hz SM SCC was highly ranked as an RF among all stimulation frequencies had better outcomes from 10 Hz treatment. CONCLUSIONS: Resonance of 10 Hz stimulation measured using SCC correlated with both symptom severity and improvement with 10 Hz rTMS treatment. Research should determine whether this interrogation paradigm can identify individualized rTMS treatment frequencies.

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder.

BACKGROUND: Intermittent theta-burst stimulation priming (iTBS-P) can improve clinical outcome of patients with Major Depressive Disorder (MDD) who do not show early benefit from 10 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC), also known as high-frequency left-sided (HFL) stimulation. The intensity and pulse number for iTBS-P needed to induce clinical benefit have not been systematically examined. OBJECTIVE: To study the effect of intensity and pulse number on the clinical efficacy of iTBS-P. METHODS: We conducted a retrospective review of 71 participants who received at least five sessions of HFL with limited clinical benefit and received iTBS-P augmentation for between 5 and 25 sessions. Intensity of iTBS-P priming stimuli ranged from 75 to 120% of motor threshold (MT) and pulse number ranged from 600 to 1800. Associations among intensity, pulse number, and clinical outcome were analyzed using a mixed methods linear model with change in IDS-SR as the primary outcome variable, priming stimulation intensity (subthreshold or suprathreshold), pulse number (<1200 or >1200 pulses), and gender as fixed factors, and number of iTBS-P treatments and age as continuous covariates. RESULTS: Subjects who received subthreshold intensity iTBS-P experienced greater reduction in depressive symptoms than those who received suprathreshold iTBS-P (p = 0.011) with no effect of pulse number after controlling for stimulus intensity. CONCLUSIONS: Subthreshold intensity iTBS-P was associated with greater clinical improvement than suprathreshold stimulation. This finding is consistent with iTBS-P acting through homeostatic plasticity mechanisms.

Individual alpha frequency proximity associated with repetitive transcranial magnetic stimulation outcome: An independent replication study from the ICON-DB consortium.

OBJECTIVE: The aim of the current study was to attempt to replicate the finding that the individual alpha frequency (IAF) as well as the absolute difference between IAF and 10 Hz stimulation frequency (IAF-prox) is related to treatment outcome. METHODS: Correlations were performed to investigate the relationship between IAF-prox and percentage symptom improvement in a sample of 153 patients with major depressive disorder treated with 10 Hz (N = 59) to the left dorsolateral prefrontal cortex (DLPFC) or 1 Hz (N = 94) to the right DLPFC repetitive Transcranial Magnetic Stimulation (rTMS). RESULTS: There was a significant negative correlation between IAF-prox and the percentage of symptom improvement only for the 10 Hz group. Curve fitting models revealed that there was a quadratic association between IAF and treatment response in the 10 Hz group, with a peak at 10 Hz IAF. CONCLUSION: The main result of Corlier and colleagues was replicated, and the findings suggest that the distance between 10 Hz stimulation frequency and the IAF may influence clinical outcome in a non-linear manner. SIGNIFICANCE: rTMS is often administered at a frequency of 10 Hz, which is the center of the EEG alpha frequency band. The results can make a significant contribution to optimizing the clinical application of rTMS.

Resting EEG theta connectivity and alpha power to predict repetitive transcranial magnetic stimulation response in depression: A non-replication from the ICON-DB consortium.

OBJECTIVE: Our previous research showed high predictive accuracy at differentiating responders from non-responders to repetitive transcranial magnetic stimulation (rTMS) for depression using resting electroencephalography (EEG) and clinical data from baseline and one-week following treatment onset using a machine learning algorithm. In particular, theta (4-8 Hz) connectivity and alpha power (8-13 Hz) significantly differed between responders and non-responders. Independent replication is a necessary step before the application of potential predictors in clinical practice. This study attempted to replicate the results in an independent dataset. METHODS: We submitted baseline resting EEG data from an independent sample of participants who underwent rTMS treatment for depression (N = 193, 128 responders) (Krepel et al., 2018) to the same between group comparisons as our previous research (Bailey et al., 2019). RESULTS: Our previous results were not replicated, with no difference between responders and non-responders in theta connectivity (p = 0.250, Cohen's d = 0.1786) nor alpha power (p = 0.357, ηp2 = 0.005). CONCLUSIONS: These results suggest that baseline resting EEG theta connectivity or alpha power are unlikely to be generalisable predictors of response to rTMS treatment for depression. SIGNIFICANCE: These results highlight the importance of independent replication, data sharing and using large datasets in the prediction of response research.

Strategies for augmentation of high-frequency left-sided repetitive transcranial magnetic stimulation treatment of major depressive disorder.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective intervention for treatment-resistant Major Depressive Disorder (MDD). Early improvement during high-frequency left-sided (HFL) stimulation of the dorsolateral prefrontal cortex (DLPFC) is an important predictor of longer-term outcome, but most patients benefit later in their treatment course. We examined patients without early improvement with HFL to determine whether augmentation with additional stimulation approaches improved treatment outcome. METHODS: 139 participants received HFL in a measurement-based care paradigm. Participants who achieved < 20% improvement by treatment 10 could continue with HFL (N = 17) or receive one of two augmentation strategies: bilateral stimulation (BL; HFL followed by low-frequency stimulation of right DLPFC) (N = 69) or intermittent theta-burst priming of left DLPFC (iTBS-P) (N = 17) for their remaining treatment sessions. The primary outcome was the percent reduction in depressive symptoms at treatment 30. RESULTS: Participants who achieved < 20% improvement by treatment 10 and continued with HFL showed limited benefit. iTBS-P participants had significantly greater improvement, while those receiving BL trended toward improved outcomes. Ten sessions of either augmentation strategy appeared necessary to determine the likelihood of benefit. CONCLUSIONS: Augmentation of early non-response to HFL appears to improve rTMS outcomes, with a novel iTBS-P strategy surpassing both continued HFL or BL treatment in participants with < 20% improvement after 10 treatments. These findings suggest that measurement-based care with addition of augmented stimulation for those not showing early improvement may yield superior rTMS treatment outcomes.

Effect of repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD) on cognitive control.

BACKGROUND: Major Depressive Disorder (MDD) is commonly accompanied by cognitive control dysfunction that may persist after remission of clinical symptoms with antidepressant medication treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment alternative for medication-resistant MDD. In this study, we investigated whether rTMS treatment had a beneficial effect not only on depressive symptoms, but on also cognitive control dysfunction. METHODS: 77 subjects with MDD received a 30-session treatment course of 10 Hz rTMS administered at the left dorsolateral prefrontal cortex (DLPFC). Treatment efficacy was assessed using the Inventory of Depressive Symptomatology Self-Rated (IDS-SR) before and after treatment, with clinical response defined as 50% or greater decrease in the IDS-SR score at treatment 30. Cognitive control function was assessed before and after treatment using the Stroop word-color interference task. We examined changes in Stroop accuracy and reaction time for congruent and incongruent trials, as well as in relation to changes in depressive symptoms. RESULTS: Performance accuracy improved particularly for the rTMS responders in the incongruent condition, with older subjects benefitting most from the rTMS treatment. Improvement in reaction times was positively associated with clinical improvement, especially in the incongruent condition. LIMITATIONS: We used a single cognitive task in a naturalistic setting without control for individual rTMS treatment parameters or concomitant medication. CONCLUSIONS: Overall, these results indicate that rTMS treatment for MDD has beneficial effects on psychomotor speed and cognitive control. Future studies should extend these findings to larger patient populations and other cognitive domains.