Martin Myczkowski

Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: A double-blind placebo-controlled study

BACKGROUND Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cortex, and the treatment of depression is one of its potential therapeutic applications. Three recent meta analyses strongly suggest its benefits in the treatment of depression. The present study investigates whether repetitive TMS (rTMS) accelerates the onset of action and increases the therapeutic effects of amitriptyline. METHODS Forty-six outpatients meeting DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial. All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of motor threshold and 1250 pulses per session). Sham stimulation followed the same schedule, however, using a sham coil. The efficacy variables were the Hamilton Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression (CGI). Tolerability was assessed by clinical examination and a safety screening of TMS side effects. RESULTS Repetitive TMS had a significantly faster response to amitriptyline. There was a significant decrease in HAM-D/17 scores, already after the first week of treatment (p < .001 compared with baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study (p < .001 at fourth week). CONCLUSIONS Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline.

Repetitive Transcranial Magnetic Stimulation Is Efficacious as an Add-On to Pharmacological Therapy in Complex Regional Pain Syndrome (CRPS) Type I

UNLABELLED Single-session repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) is effective in the treatment of chronic pain patients, but the analgesic effect of repeated sessions is still unknown. We evaluated the effects of rTMS in patients with refractory pain due to complex regional pain syndrome (CRPS) type I. Twenty-three patients presenting CRPS type I of 1 upper limb were treated with the best medical treatment (analgesics and adjuvant medications, physical therapy) plus 10 daily sessions of either real (r-) or sham (s-) 10 Hz rTMS to the motor cortex (M1). Patients were assessed daily and after 1 week and 3 months after the last session using the Visual Analogical Scale (VAS), the McGill Pain Questionnaire (MPQ), the Health Survey-36 (SF-36), and the Hamilton Depression (HDRS). During treatment there was a significant reduction in the VAS scores favoring the r-rTMS group, mean reduction of 4.65 cm (50.9%) against 2.18 cm (24.7%) in the s-rTMS group. The highest reduction occurred at the tenth session and correlated to improvement in the affective and emotional subscores of the MPQ and SF-36. Real rTMS to the M1 produced analgesic effects and positive changes in affective aspects of pain in CRPS patients during the period of stimulation. PERSPECTIVE This study shows an efficacy of repetitive sessions of high-frequency rTMS as an add-on therapy to refractory CRPS type I patients. It had a positive effect in different aspects of pain (sensory-discriminative and emotional-affective). It opens the perspective for the clinical use of this technique.

Comparison of repetitive transcranial magnetic stimulation and electroconvulsive therapy in unipolar non-psychotic refractory depression: a randomized, single-blind study

Repetitive transcranial magnetic stimulation (rTMS) can induce significant antidepressant effects and, for some patients, might be an alternative to electroconvulsive therapy (ECT). The results of studies comparing the efficacy of rTMS and ECT are mixed and, therefore, comparison of these two therapies needs to be further explored. Forty-two patients aged between 18 and 65 yr, referred to ECT due to unipolar non-psychotic depression refractoriness entered the trial. They were randomly assigned to receive either rTMS or ECT. Depressive symptom changes were blindly measured by Hamilton Depression Rating Scale, Visual Analogue Scale and Clinical Global Impression at baseline, after 2 wk and after 4 wk of treatment. There was no difference in the antidepressant efficacy of ECT and rTMS. Response rates were relatively low in both groups (40% and 50% respectively), with no significant difference between them (p=0.55). Remission rates were also low for both groups (20% and 10% respectively), also with no significant difference (p=0.631). There was no significant difference in the neuropsychological test performance after either one of these therapies. Both treatments were associated with a degree of improvement in refractory depression and therefore add to the literature that rTMS can be an effective option to ECT as it is a less costly treatment and is not associated with anaesthetic and other ECT risks.

Effects of deep brain stimulation on pain and other nonmotor symptoms in Parkinson disease

Objective: To prospectively evaluate the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the different characteristics of pain and other nonmotor symptoms (NMS) in patients with Parkinson disease (PD). Methods: Forty-four patients with PD and refractory motor symptoms were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. The primary outcome was change in pain prevalence after surgery. Secondary outcome measures were changes in motor function (Unified Parkinsons Disease Rating Scale), characteristics of pain and other NMS using specific scales and questionnaires, and quality of life. Results: Forty-one patients completed the study. The prevalence of pain changed from 70% to 21% after surgery (p < 0.001). There were also significant improvements in pain intensity, NMS, and quality of life after STN-DBS (p < 0.05). Dystonic and musculoskeletal pain responded well to DBS, while central pain and neuropathic pain were not influenced by surgery. There was a strong correlation between the change in pain intensity and the improvement in quality of life (r = 0.708, p < 0.005). No correlation was found between pain improvement and preoperative response to levodopa or motor improvement during stimulation (r = 0.247, p = 0.197 and r = 0.249, p = 0.193, respectively) or with changes in other NMS. Conclusions: STN-DBS decreased pain after surgery, but had different effects in different types of PD-related pain. Motor and nonmotor symptom improvements after STN-DBS did not correlate with pain relief. Classification of evidence: This study provides Class IV evidence that in patients with idiopathic PD with refractory motor fluctuations, STN-DBS decreases the prevalence of pain and improves quality of life.

Subthalamic deep brain stimulation modulates small fiber–dependent sensory thresholds in Parkinson’s disease

TOC summary Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with Parkinson’s disease and specifically modulates small fiber–mediated sensations. ABSTRACT The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson’s disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off‐medication condition with the stimulator turned on or off (on‐ and off‐stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age‐matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P = .019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off‐stimulation condition. In the on‐stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber–mediated sensations.

Transcranial Magnetic Stimulation to Address Mild Cognitive Impairment in the Elderly: A Randomized Controlled Study

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique with potential to improve memory. Mild cognitive impairment (MCI), which still lacks a specific therapy, is a clinical syndrome associated with increased risk of dementia. This study aims to assess the effects of high-frequency repetitive TMS (HF rTMS) on everyday memory of the elderly with MCI. We conducted a double-blinded randomized sham-controlled trial using rTMS over the left dorsolateral prefrontal cortex (DLPFC). Thirty-four elderly outpatients meeting Petersens MCI criteria were randomly assigned to receive 10 sessions of either active TMS or sham, 10 Hz rTMS at 110% of motor threshold, 2,000 pulses per session. Neuropsychological assessment at baseline, after the last session (10th) and at one-month follow-up, was applied. ANOVA on the primary efficacy measure, the Rivermead Behavioural Memory Test, revealed a significant group-by-time interaction (p = 0.05), favoring the active group. The improvement was kept after one month. Other neuropsychological tests were heterogeneous. rTMS at 10 Hz enhanced everyday memory in elderly with MCI after 10 sessions. These findings suggest that rTMS might be effective as a therapy for MCI and probably a tool to delay deterioration.

Effects of repetitive transcranial magnetic stimulation on clinical, social, and cognitive performance in postpartum depression.

Background: This randomized, placebo-controlled, double-blind pilot study evaluated the impact of repetitive transcranial magnetic stimulation (rTMS) on clinical, cognitive, and social performance in women suffering with postpartum depression. Methods: Fourteen patients were randomized to receive 20 sessions of sham rTMS or active 5 Hz rTMS over the left dorsolateral prefrontal cortex. Psychiatric clinical scales and a neuropsychological battery were applied at baseline (pretreatment), week 4 (end of treatment), and week 6 (follow-up, posttreatment week 2). Results: The active rTMS group showed significant improvement 2 weeks after the end of rTMS treatment (week 6) in Hamilton Depression Rating Scale (P = 0.020), Global Assessment Scale (P = 0.037), Clinical Global Impression (P = 0.047), and Social Adjustment Scale-Self Report-Work at Home (P = 0.020). Conclusion: This study suggests that rTMS has the potential to improve the clinical condition in postpartum depression, while producing marginal gains in social and cognitive function.

Treatment of Bipolar Depression with Deep TMS: Results from a Double-Blind, Randomized, Parallel Group, Sham-Controlled Clinical Trial

Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. We conducted a randomized sham-controlled trial to evaluate the efficacy and safety of dTMS in treatment-resistant BD patients. Patients received 20 sessions of active or sham dTMS over the left dorsolateral prefrontal cortex (H1-coil, 55 18 Hz 2 s 120% MT trains). The primary outcome was changes in the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to endpoint (week 4). Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Safety was assessed using a dTMS adverse effects questionnaire and the Young Mania Rating Scale to assess treatment-emergent mania switch (TEMS). Out of 50 patients, 43 finished the trial. There were 2 and 5 dropouts in the sham and active groups, respectively. Active dTMS was superior to sham at end point (difference favoring dTMS=4.88; 95% CI 0.43 to 9.32, p=0.03) but not at follow-up. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR=2.92; 95% CI=0.87 to 9.78, p=0.08). Remission rates were not statistically different. No TEMS episodes were observed. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy.

Preliminary Results: Transcranial magnetic stimulation improves memory and attention in elderly with cognitive impairment no-dementia (CIND)—A controlled study

Background:Normal aging is associated with cognitive impairments, often overlooked in medical practice, especially in milder forms, with significant impact on quality of life. Such cognitive decline has not, up to date, specific treatment approach, leaving a gap in the therapeutic arsenal of both specialist and general practitioner. Repetitive transcranial magnetic stimulation (rTMS) is a promising noninvasive and painless technique. It has the potential to improve cognition in elderly activating neural networks, and provides an attractive option as strategy to enhance cognitive abilities, especially memory, in older subjects. The objective of this study is to assess the effects of high frequency rTMS to the dorsolateral prefrontal cortex (DLPFC) on global cognition of functionally independent elderly with subjective complaints of memory impairment. Methods: Clinical trial. Nineteen (8 male and 11 female) elderly, aged between 60 and 74 years old (mean age 1⁄4 64.5 6 3.8), independent for instrumental activities of daily living (IADL) with subjective memory complaints and evidence of some impairment in neuropsychological assessment, characterizing cognitive impairment no-dementia. The MoCA test was used for screening. For each patient, a brain magnetic resonance Table 2 Reversal of scopolamine induced amnesia by Ageratum conyzoides of EPM model in young mice

Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial

BACKGROUND Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that present cognitive safety. In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. METHODS Fourty-three patients were randomized to receive 20 sessions of active (55 trains, 18 Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of 20 neuropsychological assessments, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline and after 4 and 8 weeks of trial onset. Depressive symptoms were assessed with the 17-item Hamilton Rating Scale for Depression. RESULTS Cognitive improvement was shown for all cognitive domains. It occurred regardless of intervention group and depression improvement. For the language domain, greater improvement was observed in the sham group over time. No correlations between depression (at baseline or during treatment) and cognitive improvement were found. LIMITATIONS Absence of healthy control group. CONCLUSION The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients. Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated.