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.

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 Petersen's 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.

Placebo effect after prefrontal magnetic stimulation in the treatment of resistant obsessive-compulsive disorder: a randomized controlled trial.

Many patients with obsessive-compulsive disorder (OCD) do not achieve satisfactory symptom improvement with conventional treatments. Here, we evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) applied over the right dorsolateral prefrontal cortex (rDLPFC) in patients with treatment-resistant OCD. This was a double-blind randomized trial involving 30 treatment-resistant OCD outpatients, allocated to have either sham or active high-frequency rTMS (over the rDLPFC) added to their treatment regimens for 6 wk, with 6 wk of follow-up. Active rTMS consisted of 30 applications (figure-of-eight coil; 10 Hz at 110% of motor threshold; 1 session/d; 40 trains/session; 5 s/train; 25-s intertrain interval). At weeks 0, 2, 6, 8, and 12, we applied the Yale-Brown Obsessive-Compulsive Scale (YBOCS), Clinical Global Impression (CGI) scale, 14-item Hamilton Anxiety Rating Scale (HAMA-14), 17-item Hamilton Depression Rating Scale (HAMD-17), and 36-item Short-form Health Survey. The primary outcome measure was a positive response (≥ 30% improvement in YBOCS score, together with a 'much improved' or 'very much improved' CGI - Improvement scale rating). One patient in each group showed a positive response (p=1.00). For YBOCS score, there was significant effect of time (F=7.33, p=0.002) but no significant group effect or group×time interaction. In treatment-resistant OCD, active rTMS over the rDLPFC does not appear to be superior to sham rTMS in relieving obsessive-compulsive symptoms, reducing clinical severity, or improving treatment response, although there is evidence of a placebo effect.

Whole field tendencies in transcranial magnetic stimulation: A systematic review with data and text mining.

BACKGROUND: Transcranial magnetic stimulation (TMS) has played an important role in the fields of psychiatry, neurology and neuroscience, since its emergence in the mid-1980s; and several high quality reviews have been produced since then. Most high quality reviews serve as powerful tools in the evaluation of predefined tendencies, but they cannot actually uncover new trends within the literature. However, special statistical procedures to 'mine' the literature have been developed which aid in achieving such a goal. OBJECTIVES: This paper aims to uncover patterns within the literature on TMS as a whole, as well as specific trends in the recent literature on TMS for the treatment of depression. METHODS: Data mining and text mining. RESULTS: Currently there are 7299 publications, which can be clustered in four essential themes. Considering the frequency of the core psychiatric concepts within the indexed literature, the main results are: depression is present in 13.5% of the publications; Parkinson's disease in 2.94%; schizophrenia in 2.76%; bipolar disorder in 0.158%; and anxiety disorder in 0.142% of all the publications indexed in PubMed. Several other perspectives are discussed in the article.

Envenamentos por psicofármacos / Poisoning by psychotropic

O envenenamento por psicofármacos figura entre as intoxicações exógenas intencionais ou acidentais como causa freqüente de atendimentos médico-hospitalares, com considerável taxa de morbidade e mortalidade. Este artigo tem por objetivo apresentar dados epidemiológicos relevantes e revisar a conduta preconizada para estes casos, sumarizando cuidados em relação à obtenção de história clínica, exame físico e complementar, suporte básico e especializado. Procura também sistematizar as diretrizes para indicar encaminhamento à Unidade de Terapia Intensiva, internação e/ou avaliação psiquiátrica especializada.

Hand function improvement with low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere in a severe case of stroke.

Previous research has shown that low-frequency rTMS of the unaffected hemisphere can improve motor function in acute and chronic stroke patients. However, these studies only investigated patients with mild or moderate motor deficits. We report a case of a stroke patient with a severe motor impairment who underwent sham and active repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere and had significantly improved motor function after active, but not after sham, stimulation of the unaffected primary motor cortex. In an additional session of active rTMS, this patient maintained and further enhanced the initial motor improvement. This case report shows that inhibitory rTMS of the unaffected hemisphere can also be beneficial for stroke patients with severe motor deficits and suggests that this approach of noninvasive brain stimulation should be further investigated in this population of patients.

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.

Transcranial direct current stimulation of the unaffected hemisphere in stroke patients.

Recovery of function after a stroke is determined by a balance of activity in the neural network involving both the affected and the unaffected brain hemispheres. Increased activity in the affected hemisphere can promote recovery, while excessive activity in the unaffected hemisphere may represent a maladaptive strategy. We therefore investigated whether reduction of the excitability in the unaffected hemisphere by cathodal transcranial direct current stimulation could result in motor performance improvement in stroke patients. We compared these results with excitability-enhancing anodal transcranial direct current stimulation of the affected hemisphere and sham transcranial direct current stimulation. Both cathodal stimulation of the unaffected hemisphere and anodal stimulation of the affected hemisphere (but not sham transcranial direct current stimulation) improved motor performance significantly. These results suggest that the appropriate modulation of bihemispheric brain structures can promote motor function recovery.

Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson's disease and concurrent depression.

Previous studies show that cognitive functions are more impaired in patients with Parkinson's disease (PD) and depression than in nondepressed PD patients. We compared the cognitive effects of two types of antidepressant treatments in PD patients: fluoxetine (20 mg/day) versus repetitive transcranial magnetic stimulation (rTMS, 15 Hz, 110% above motor threshold, 10 daily sessions) of the left dorsolateral prefrontal cortex. Twenty-five patients with PD and depression were randomly assigned either to Group 1 (active rTMS and placebo medication) or to Group 2 (sham rTMS and fluoxetine). A neuropsychological battery was assessed by a rater blind to treatment arm at baseline and 2 and 8 weeks after treatment. Patients in both groups had a significant improvement of Stroop (colored words and interference card) and Hooper and Wisconsin (perseverative errors) test performances after both treatments. Furthermore, there were no adverse effects after either rTMS or fluoxetine in any neuropsychological test of the cognitive test battery. The results show that rTMS could improve some aspects of cognition in PD patients similar to that of fluoxetine. The mechanisms for this cognitive improvement are unclear, but it is in the context of mood improvement.

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.

Aplicação da estimulação magnética transcraniana de repetição no tratamento do transtorno obsessivo-compulsivo e outros transtornos de ansiedade / Repetitive transcranial magnetic stimulation as a treatment for obsessive-compulsive disorder and other anxiety disorders

A estimulação magnética transcraniana de repetição (EMTr) vem sendo amplamente investigada como ferramenta terapêutica em transtornos psiquiátricos, especialmente a depressão. Neste trabalho, compilamos as informações provenientes de estudos que investigaram as aplicações da EMTr no tratamento dos transtornos de ansiedade: transtorno do pânico (TP), transtorno de estresse pós-taumático (TEPT), transtorno de ansiedade generalizada (TAG) e especialmente o transtorno obsessivo compulsivo (TOC). Três estudos foram publicados abordando o tratamento do TOC, sendo que utilizaram metodologias e parâmetros de aplicação extremamente diversos, dificultando a obtenção de informações conclusivas sobre a efetividade deste tratamento. Quatro estudos publicados sobre TEPT e EMTr também apresentam dados conflitantes e pouco comparáveis, mas destaca-se publicação recente com desenho duplo-cego e resultados positivos. Quanto ao TP e o TAG, apenas pequenas investigações iniciais foram realizadas. Conclusão: Apesar dos estudos citados, não há dados conclusivos sobre a eficácia terapêutica da EMTr nos transtornos de ansiedade. Isto se dá especialmente devido aos estudos com amostras pequenas e desenho aberto. Portanto, devem ser realizados estudos mais aprofundados para que possamos obter estas respostas.