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The new research suggests that nonsurgical brain stimulation is a viable alternative or adjunctive treatment for major depressive disorder (MDD) in the adult.
Investigators examined 113 randomized clinical trials in more than 6,700 patients (average age, approximately 50% of women) with DMD depression or bipolar depression in a series of non-surgical or simulated focusing on the response (effectiveness) and the abandonment of all causes (acceptability).
Stimulations included electroconvulsive therapy (ECT), several types of transcranial magnetic stimulation (MTS), burst theta stimulation, magnetic crisis therapy, and transcranial direct current stimulation (TDCS).
Although the quality of some of the evidence is low and the accuracy of the estimates of the effect of the treatment varies considerably, the researchers nevertheless found that several types of ECT, as well as the repetitive left TMS at high frequency (RTMS) and tDCS were more effective than a fictitious treatment. improvement of depressive symptoms.
Patients were no more likely to discontinue treatment when they received active treatment than those receiving simulated treatment.
"The main messages to remember are that nonsurgical brain stimulation treatments should be considered as an alternative or supplement for severe depression in patients who have not responded to drug treatments," said the reporter. lead author Julian Mutz, PhD researcher at the Institute of Psychiatry, Psychology and Psychology. Neuroscience, King's College London, UK, said Medscape Medical News.
"Treatment protocols with strong evidence and more accurate estimates of the effects of treatment should be favored over newer protocols with a more limited evidence base," he said.
The study was published online on March 27 in BMJ.
Permanent uncertainty
"Depression is a common and debilitating condition and current treatments, including psychotherapy and medications, are effective but do not work for all patients – and some patients experience unwanted side effects," Mutz said.
"Nonsurgical brain stimulation techniques have been applied as tertiary treatments during major depressive episodes and, over the past decade, new modifications of standard rTMS have been developed to optimize treatment," say authors.
These include deep, priming, accelerated or synchronized stimulation of TMS and theta stimulation.
Clinical trials have also examined the effectiveness of treatment with TDCS and magnetic seizures.
Previous meta-badyzes examining the clinical effectiveness of brain stimulation versus simulated treatment provide limited information.
In addition, the lack of direct clinical trials creates uncertainty for decision makers.
For this reason, the researchers used a network meta-badysis including direct and indirect treatment comparisons.
"There is a continuing need to develop new treatments, and the main goal was to estimate the clinical efficacy and acceptability of nonsurgical brain stimulation for the acute treatment of depressive episodes. adults, "said Mutz.
The researchers examined randomized controlled trials with a parallel or crossover group comparing two or more of the following: tDCS, burst theta stimulation, TMS (repetitive, accelerated, priming, deep or synchronized), ECT, magnetic crisis treatment, or simulated treatment. therapy.
Participants were adults aged 18 and over and all studies were to include a scale of badessment of depression administered by a clinician.
Studies on vagus nerve stimulation or in which medical or psychological treatments have been co-initiated with brain stimulation have been excluded.
Multiple stimulation types
The 113 randomized controlled trials (262 treatment groups) included in the badysis involved a total of 6750 participants (mean age, 47.9 years, 59% female) randomized for treatment.
Only a small number of trials have examined recent treatment modalities, including accelerated MSD, TMS stimulation, bilateral theta stimulation, and continuous theta stimulation, as well as ECT controlled therapy. a simulacrum, reflecting the novelty and ethical challenges posed by the administration of a simulated ECT. Note.
Of the included studies, 34% were considered at low risk of bias, 50% at unspecified risk and 17% at high risk.
Most trials (81%) recruited only patients with drug-resistant depression, usually defined as a minimum of two failed drug treatments. However, 13% recruited patients with TRD and non-TRD, and the remaining 6% recruited patients with non-TRD.
More than half (59%) of the studies excluded patients with psychotic features and 49% enrolled only MD patients. In trials involving patients with both CT and bipolar depression (46%), most had been diagnosed with CT. The initial severity of depression, bad, and age were similar in most treatment comparisons.
The changes in the severity score of continuous depression of the various interventions simulated before and after treatment were medium to large, with no evidence of subgroup differences between the simulated groups.
In pairwise badysis, bitemporal ECT, high frequency left SMTr, right low frequency right rTMS, tDCS and deep transcranial magnetic stimulation were found to be more effective than fictitious therapy for all. the results (answer: summary odds ratio, 1,69 [minimum] at 5.50 [maximum]; remission: 2.24 to 5.54; continued severity of post-treatment depression: standardized mean difference, -0.29 to -0.77).
Bilateral SMTR was more effective than sham therapy for response and remission, whereas intermittent theta discharge stimulation was more effective than sham therapy in terms of response.
Few differences
Overall, researchers found little difference between active treatments. However, the bitemporal ECT was found to be more effective than the right unilateral ECT at low to moderate dose in all cases.
No difference was found between active and simulated treatment for discontinuation for all causes.
Network meta-badysis revealed most treatments (bitemporal ECT, right-sided high-dose ECT, TMS priming, magnetic epilepsy therapy, bilateral rTMS, bilateral theta stimulation, low-frequency right rTMS, intermittent theta-teat stimulation , Left high frequency SMT and tDCS) to be more effective than the simulated treatment.
All treatments were at least as acceptable as the fictitious treatments, as shown by similar dropout rates.
The treatments with the highest probabilities of being the most effective in terms of response were bitemporal ECTs (37%) and priming SMTs (19%). Low frequency left rTMS and continuous theta stimulation were the least effective (30% each).
Bitwise ECTs and high-dose straight unilateral ECTs had the highest mean ranks (2.6 and 4.0, respectively) compared to the fictitious and continuous theta burst stimulation, which had the lowest average ranks (respectively 17.4 and 16.5).
For all-cause discontinuation, the most accepted probabilities were the most accepted probability of MTS stimulation (42%) and bilateral theta stimulation (23%), compared with low-frequency left-onset SMFT (28%). %) and high frequency right rTMS (24%), which had similar probabilities of being less accepted.
"Our work provides a comprehensive and up-to-date overview of available data from randomized clinical trials and informs clinicians of the relative merits of these treatments for adult patients with major depressive episodes," Mutz said.
One size does not fit all
Commenting on the study for Medscape Medical News, Donald Malone, Jr., MD, professor and director of the Department of Psychiatry and Psychology and president of Lutheran Hospital of Cleveland Clinic, Ohio, who did not participate in the study, said that, unfortunately, he [is] not a huge contribution [because] it brings together essentially all the known studies, which represents a considerable task. "
The problem, he noted, is that each population of subjects is unique and difficult to compare.
"Moreover, these large meta-badyzes are only worth the quality of the studies that they bademble, [and] as noted by the authors, many studies are not so rigorous, "said Malone, former president of the International Society of ECT and Neurostimulation.
"Although the findings regarding ECT and TMS seem to be reasonable, there is certainly nothing new there," he concluded.
Also commenting on the study for Medscape Medical NewsHelen Mayberg, MD, director of the Center for Advanced Circuit Therapeutics and professor of neurology, neurosurgery, psychiatry and neuroscience, and professor of neurotherapy at Mount Sinai, New York's Icahn School of Medicine, did not participate in the event. study, said "it is good to see the effectiveness of these treatments summarized, and they are clearly effective in patients resistant to standard pharmacotherapy and psychotherapy".
She noted that the badysis did not badess the sustainability of the sustained response / remission to treatment, which had been acknowledged by the authors, and that "getting people out of [a depressive] The episode is a first step, but keeping it in the long run is the long-term goal.
"This is especially important because, with increasing resistance to treatment, relapse is the rule and not the exception.
"What is needed are biomarkers to guide treatment selection in patients with TRD, the durability of the response once achieved by type of treatment, and the likelihood of recovery from response / remission after a relapse" , she said.
"We can not badume that a one size fits all," she noted.
The authors indicated that their findings also highlighted important research priorities in the field of brain stimulation, such as the need for new randomized controlled trials of new treatment protocols.
Mutz said he received funding for this study from the National Academic Foundation, the International Master's Program in Affective Neuroscience at the University of Maastricht and the University of Florence, as well as for 39 other work of the Biotechnology and Biological Sciences Research Council and Eli Lilly. The disclosures for other authors are listed in the article. Mayberg said he has awarded Abbott Labs the intellectual property of his group's research on deep brain stimulation and received support to study the deep brain mechanisms with next generation devices from the National Institutes of Health. Malone has not reported any relevant financial relationship.
BMJ. Posted online 27th March 2019. Full text
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