Although previous clinical trials have suggested that repetitive transcranial magnetic stimulation (rTMS) has a significant antidepressant effect, the results of these trials are heterogeneous. We hypothesized that individual patients' characteristics might contribute to such heterogeneity. Our aim was to identify predictors of antidepressant response to rTMS. We pooled data from six separate clinical trials conducted independently, which evaluated the effects of rapid rTMS of the left dorsolateral prefrontal cortex in patients with major depression. We investigated 195 patients with regard to demographic, depression and treatment characteristics, psychiatric and drug history. Results showed that age and treatment refractoriness were significant negative predictors of depression improvement when adjusting these variables to other significant predictors and confounders. These findings were not confounded by methodological differences from the six studies, as the results were adjusted for the study site. In conclusion TMS antidepressant therapy in younger and less treatment-resistant patients is associated with better outcome.

In this paper we review the parameters that define the ECT electrical stimulus and discuss their biophysical roles. We also present the summary metrics of charge and energy that are conventionally used to describe the dose of ECT and the rules commonly deployed to individualize the dose for each patient. We then highlight the limitations of these summary metrics and dosing rules in that they do not adequately capture the roles of the distinct stimulus parameters. Specifically, there is strong theoretical and empirical evidence that stimulus parameters (pulse amplitude, shape, and width, and train frequency, directionality, polarity, and duration) exert unique neurobiological effects that are important for understanding ECT outcomes. Consideration of the distinct stimulus parameters, in conjunction with electrode placement, is central to further optimization of ECT dosing paradigms to improve the risk/benefit ratio. Indeed, manipulation of specific parameters, such as reduction of pulse width and increase in number of pulses, has already resulted in dramatic reduction of adverse side effects, while maintaining efficacy. Furthermore, the manipulation of other parameters, such as current amplitude, which are commonly held at fixed, high values, might be productively examined as additional means of targeting and individualizing the stimulus, potentially reducing side effects. We recommend that ECT dose be defined using all stimulus parameters rather than a summary metric. All stimulus parameters should be noted in treatment records and published reports. To enable research on optimization of dosing paradigms, we suggest that ECT devices provide capabilities to adjust and display all stimulus parameters.

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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.

Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation.

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). Method: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. results: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. Discussion: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches. Key words: comprehensive review, major depressive disorder, ECT, TMS, clinical guidelines.Estratégias de neuromodulação para o tratamento da depressão maior: desafios e recomendações de uma força-tarefa rEsuMo O uso de técnicas de neuromodulação para o tratamento do transtorno depressivo maior (TDM) tem despertado um renovado interesse nos últimos anos com o desenvolvimento de outras intervenções não-farmacólogicas além da eletroconvulsoterapia (ECT), como a estimulação magnética transcraniana (EMT), a estimulação transcraniana por corrente continua (ETCC), a estimulação cerebral profunda (DBS) e a estimulação de nervo vago (VNS). Método: Nós organizamos um grupo de trabalho com vários pesquisadores para discutir os avanços recentes e os principais desafios para o uso da neuromodulação no tratamento os principais desafios da pesquisa na neuromodulação e alternativas para superá-los. Discussão: ECT é o tratamento de primeira linha para depressão grave. EMT e ETCC são estratégias com um perfil benigno de efeitos adversos; contudo, enquanto os efeitos da EMT são comparáveis ao das drogas antidepressivas para o tratamento da TDM, a eficácia da ETCC ainda precisa ser estabelecida por mais pesquisas clínicas. DBS e VNS são intervenções invasivas com um papel possível para a depressão refratária. Em resumo, TDM é uma condição crônica, incapacitante e de alta prevalência; portanto na prática clínica todas as opções de tratamento possíveis, incluindo as farmacológicas e não-farmacológicas, devem ser consideradas. Palavras-chave: artigo de revisão, tra...

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.

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