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[Ethical considerations regarding the use of transcranial magnetic stimulation in the treatment of depression]
Abstract
Transcranial magnetic stimulation (TMS) has proved effective in the treatment of depression. However, the step that was needed to progress from positive research results to the actual use of TMS to treat patients has raised a number of ethical concerns. The concerns extend beyond matters such as the safety of the technique, the patient's right of access to therapy and the patient's informed consent; ethics are involved because the new treatment can be mind-bending and can interfere with the patient's autonomy and decision-making capacity.
To discuss ethical issues raised by the use of TMS in the treatment of depression.
We reviewed the relevant scientific literature.
The effects of the treatment on the patient's genuine wishes and on his or her views on the efficacy of the treatment are technique-related ethical issues that have not yet been adequately addressed. Furthermore, the effects of TMS on the patient's autonomy and mental capacity and the 'last resort' argument in relation to the effectiveness of the therapy are context-related considerations that warrant further discussion.
There will have to be more research and discussion among researchers and clinicians about specific ethical questions before TMS can take its rightful place in clinical practice.
... TMS is also being questioned, like other neuromodulation techniques, for its ability to affect patient autonomy and alter decision making capacity. 32 Here, we review different original studies done to date to investigate the use of TMS in reducing subjective aspects of craving and/or impulsivity in AUD patients. ...
Background and objective
In the US, about 14.5 million people ages 12 and older suffered from alcohol use disorder (AUD) in 2019. AUD affects multiple systems and is a major cause of disability and morbidity, severely reducing quality of life. With currently available pharmacotherapy and psychotherapy (including behavioral therapy) relapse rates remain high due to poor patient acceptability as well as the added factor of craving and impulsivity in addiction disorders. This points to development of therapies that also act on functional areas of brain responsible for craving and impulsivity. Transcranial magnetic stimulation (TMS) is one type of neuromodulation under study for the treatment of AUD. Here, we review the work done on TMS as a treatment for AUD.
Methods
We searched PubMed and Cochrane databases for relevant articles with main search terms of “transcranial magnetic stimulation” and “alcoholism”.
Results
Most studies involve stimulation of right dorsolateral prefrontal cortex. Majority demonstrate a decrease in craving but only over time, not between groups. Overall, studies using TMS for the treatment of AUD show mixed results in changes in craving, impulsivity, and alcohol intake.
Conclusion
Mainly, the studies are limited by sample size and lack of uniformity in outcomes measured. Significance of TMS for treatment of AUD is still not clear. A standardized protocol of investigation is needed to allow for a meta-analysis to calculate the overall effect.
... Existen interrogantes éticas respecto a la seguridad de la técnica, el derecho del paciente a la evaluación de la terapia para dar su consentimiento informado y el hecho de que el nuevo tratamiento esté vinculado a la mente del paciente y pueda influir en su capacidad para la toma de decisiones y en su autonomía. [19][20][21] La estimulación cerebral profunda, aprobada para el tratamiento de la enfermedad de Parkinson, requiere de cirugía cerebral invasiva para colocar un electrodo en el sitio a estimular, la conexión y el marcapasos insertado de forma subcutánea. Se plantea que puede mejorar la memoria mediante la estimulación del lóbulo temporal medial y otras estructuras. ...
Introducción: existe una amplia variedad de intervenciones para mejorar las funciones cognitivas (potenciadores cognitivos), algunas más convencionales y otras novedosas como: drogas, implantes, interfaces directas cerebro-computadora e ingeniería genética; sin embargo, hasta la fecha la mayoría de los avances considerables en el desempeño cognitivo han sido alcanzados mediante medios no médicos.
Objetivo: describir los principales potenciadores cognitivos y los acercamientos éticos actuales. Métodos: consulta y discusión de la literatura médica sobre potenciadores cognitivos, ensayos clínicos y aspectos éticos de revistas científicas arbitradas en bases de datos como Pubmed, EBSCO Y Scielo en los últimos diez años.
Conclusiones: las cuestiones éticas involucradas en su abordaje son dependientes del beneficio esperado contra los riesgos, pues no existen estudios que describan los efectos adversos de su uso a largo plazo en sujetos sanos. Otros aspectos importantes lo constituyen la autonomía de decidir o no usarlos, los principios de equidad y justicia con la posibilidad de una distribución desigual de estos, y las preocupaciones sobre la pérdida de la autenticidad. Para que el uso de los potenciadores cognitivos sea posible, es necesaria la creación de estudios futuros aleatorizados controlados y guías éticas.
Background:
Meta-analyses have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has antidepressant properties when compared with sham rTMS. However, its overall response and remission rates in major depression (MD) remain unclear. Thus, we have systematically and quantitatively assessed the efficacy of HF-rTMS for MD based on randomized, double-blind and sham-controlled trials (RCTs).
Method:
We searched the literature from 1995 through to July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses. We used a random-effects model, odds ratios (ORs) and the number needed to treat (NNT).
Results:
Data from 29 RCTs were included, totaling 1371 subjects with MD. Following approximately 13 sessions, 29.3% and 18.6% of subjects receiving HF-rTMS were classified as responders and remitters, respectively (compared with 10.4% and 5% of those receiving sham rTMS). The pooled OR was 3.3 (p < 0.0001) for both response and remission rates (with associated NNTs of 6 and 8, respectively). Furthermore, we found HF-rTMS to be equally effective as an augmentation strategy or as a monotherapy for MD, and when used in samples with primary unipolar MD or in mixed samples with unipolar and bipolar MD. Also, alternative stimulation parameters were not associated with differential efficacy estimates. Moreover, baseline depression severity and drop-out rates at study end were comparable between the HF-rTMS and sham rTMS groups. Finally, heterogeneity between the included RCTs was not statistically significant.
Conclusions:
HF-rTMS seems to be associated with clinically relevant antidepressant effects and with a benign tolerability profile.
Introduction:
Transcranial magnetic stimulation (TMS) is a novel antidepressant therapy shown to be effective and safe in pharmacotherapy-resistant major depression. The incremental cost-effectiveness and the direct cost burden compared with sham treatment were estimated, and compared with the current standard of care.
Methods:
Healthcare resource utilization data were collected during a multicenter study (n=301) and a decision analysis was used to stratify the 9-week treatment outcomes. A Markov model with an acute-outcome severity-based risk of relapse was used to estimate the illness course over a full year of treatment follow-up. These model estimates were also compared to best estimates of outcomes and costs of pharmacotherapy treatment, using the published STAR(*)D outcomes. The cost-effectiveness of TMS was described using an incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained and on a direct cost per patient basis across a varying range of assumptions. The model's sensitivities to costs due to losses in work productivity and to caregiver time were also examined.
Results:
Compared with sham treatment and at a cost of US34,999 per QALY, which is less than the "willingness-to-pay' standard of US6667 per QALY. In open-label conditions, TMS provided a net cost saving of US7621). The overall cost benefits of treating MD using TMS were greater in those patients at the earliest levels of treatment resistance in the overall sample.
Conclusion:
TMS is a cost-effective treatment for patients who have failed to receive sufficient benefit from initial antidepressant pharmacotherapy. When used at earlier levels of treatment resistance, significant cost savings may be expected relative to the current standard of care.
The hopes and fears expressed in the debate on human enhancement are not always based on a realistic assessment of the expected
possibilities. Discussions about extreme scenarios may at times obscure the ethical and policy issues that are relevant today.
This paper aims to contribute to an adequate and ethically sound societal response to actual current developments. After a
brief outline of the ethical debate concerning neuro-enhancement, it describes the current state of the art in psychopharmacological
science and current uses of psychopharmacological enhancement, as well as the prospects for the near future. It then identifies
ethical issues regarding psychopharmacological enhancements that require attention from policymakers, both on the professional
and on the governmental level. These concern enhancement research, the gradual expansion of medical categories, off-label
prescription and responsibility of doctors, and accessibility of enhancers on the Internet. It is concluded that further discussion
on the advantages and drawbacks of enhancers on a collective social level is still needed.
The field of placebo research has made considerable progress in the last years and it has become a major focus of interest. We know now that the placebo effect is a real neurobiological phenomenon and that the brain's 'inner pharmacy' is a critical determinant for the occurrence of psychobiological and behavioural changes relevant to healing processes and well-being. However, harnessing the advantages of placebo effects in healthcare is still a challenge. The first part of the theme issue summarizes and discusses the various kinds of placebo mechanisms across medical fields, thereby not only focusing on two main explanatory models-expectation and conditioning theory-but also taking into account empathy and social learning, emotion and motivation, spirituality and the healing ritual. The second part of the issue focuses on questions related to transferring knowledge from placebo research into clinical practice and discusses implications for the design and interpretation of clinical trials, for the therapeutic settings in daily patient care, and for future translational placebo research.
This article will examine how the notion of emotional authenticity is intertwined with the notions of naturalness and artificiality in the context of the recent debates about 'neuro-enhancement' and 'neuro-psychopharmacology.' In the philosophy of mind, the concept of authenticity plays a key role in the discussion of the emotions. There is a widely held intuition that an artificial means will always lead to an inauthentic result. This article, however, proposes that artificial substances do not necessarily result in inauthentic emotions. The literature provided by the philosophy of mind on this subject usually resorts to thought experiments. On the other hand, the recent literature in applied ethics on 'enhancement' provides good reasons to include real world examples. Such case studies reveal that some psychotropic drugs such as antidepressants actually cause people to undergo experiences of authenticity, making them feel 'like themselves' for the first time in their lives. Beginning with these accounts, this article suggests three non-naturalist standards for emotions: the authenticity standard, the rationality standard, and the coherence standard. It argues that the authenticity standard is not always the only valid one, but that the other two ways of assessing emotions are also valid, and that they can even have repercussions on the felt authenticity of emotions. In conclusion, it sketches some of the normative implications if not ethical intricacies that accompany the enhancement of emotions.
Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including marketing, off-label use and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand.
Background:
The high incidence of depressive disorder in the Netherlands calls for additional forms of therapy. Transcranial magnetic stimulation (TMS) is a form of non-invasive brain stimulation that has been investigated in the last 15 years in order to find out whether this form of stimulation is effective in the treatment of depression.
Aim:
To discover whether TMS has proved effective in the treatment of depressed patients.
Results:
Results show that tms treatment is safe when applied to the frontal lobes of the cerebral cortex and that the therapeutic effect is comparable to the effect of psychotherapy and antidepressants. Future studies should concentrate on an increase in efficiency by providing more insight into the working mechanisms and the effect of individual differences. Follow-up studies are needed to investigate the duration of the antidepressive effect.
Conclusion:
TMS seems to be a promising tool for the treatment of depressive disorders. However, there are many questions and uncertainties about the efficiency and applicability of TMS.
Background
Transcranial magnetic stimulation (TMS) is a safe and effective treatment for major depression. We describe quality of life (QOL) outcomes from acute treatment with TMS, and describe the durability of benefit across 24-weeks.
Methods
Three hundred and one medication-free patients with pharmacoresistant major depression were randomized to active or sham TMS in a 6-week controlled trial. Nonresponders to the 6-week blinded phase of the study were enrolled in a 6-week open-label study without unblinding the prior treatment assignment. Responders and partial responders to both the blinded (active or sham treatment) or open acute treatment phases were tapered off TMS over three weeks, while initiating maintenance antidepressant medication monotherapy. These subjects entered the 24-week study to examine the durability of response to TMS. The Medical Outcomes Study-36 Item Short Form (SF-36) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were used to measure overall function and QOL. During the 24-week durability of effect study, QOL assessments were done at study entry and at the end of 24-weeks.
Results
Statistically significant improvement in both functional status and QOL outcomes was observed in patients treated with active TMS compared with sham TMS during the acute phase of the randomized, sham-controlled trial. Similar benefits were observed in patients who entered the open-label extension study. These improvements were sustained across the 24-week follow up study.
Conclusions
Acute treatment with TMS improved functional status and QOL outcomes in patients with major depression. This clinical effect was durable in long-term follow up.
Purpose of review:
Daily left prefrontal transcranial magnetic stimulation (TMS) for several weeks was first proposed as an acute treatment for depression in the early 1990s, and was Food and Drug Administration (FDA) approved in 2008. In the past year, several important studies have been published that extend our understanding of this novel treatment approach.
Recent findings:
The first round of multisite clinical trials with TMS addressed whether prefrontal rTMS has efficacy and were conducted in carefully selected depressed patients who were antidepressant medication free. Several more recent studies assess the clinical effectiveness of TMS and report that about 35-40% of real-world patients who are commonly taking adjunctive antidepressants reach remission with a modest side effect profile. There are also new studies examining the durability of the TMS-induced antidepressant effect. Fifty-eight percent of TMS remitters remain remitted at 3-month follow-up.
Summary:
These recent studies suggest that daily left prefrontal TMS over several weeks as a treatment for depression not only appears to have efficacy in rigorous randomized controlled trials, but is effective in real-world settings, with remission in 30-40% of patients. The TMS antidepressant effect, once achieved, appears to be as durable as with other antidepressant medications or interventions. Much more research is needed, particularly with issues such as the TMS coil location, stimulation intensity and frequency, and dosing strategy.
Neurotechnology provides means to engage micro- and macrostructural networks of the brain to both mitigate the manifestations of several neurological and psychiatric disorders, and alter cognition and motoric activity. Such capacity also generates questions of how these interventions may affect personal identity. This paper discusses the ethical implications regarding changes to personal identity that arise from the therapeutic use of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) technologies. In addition, we raise the question of whether changes in personal identity, as a side effect of these interventions, are ethically acceptable and whether such alterations of personality foster patients' sense of well-being and autonomy. First, we provide a series of case vignettes that afford an overview of the ways that various neurological interventions can affect personal identity. Second, we offer a brief working definition of personal identity in order to delineate an ethical framework that we deem necessary for the responsible use of neurostimulation technologies. In so doing, we argue that neurostimulation therapy, as a doctoring act, should be directed, and adherent to goals of restoring and/or preserving patients' personal identity. To this end, we offer an ethical framework that we believe enables sound decisions about the right and good use of TMS and DBS.
Repetitive transcranial magnetic stimulation (rTMS) is a safe treatment method with few side effects. However, efficacy for various psychiatric disorders is currently not clear.
A literature search was performed from 1966 through October 2008 using PubMed, Ovid Medline, Embase Psychiatry, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and PsycINFO. The following search terms were used: transcranial magnetic stimulation, TMS, repetitive TMS, psychiatry, mental disorder, psychiatric disorder, anxiety disorder, attention-deficit hyperactivity disorder, bipolar disorder, catatonia, mania, depression, obsessive-compulsive disorder, psychosis, posttraumatic stress disorder, schizophrenia, Tourette's syndrome, bulimia nervosa, and addiction.
Data were obtained from randomized, sham-controlled studies of rTMS treatment for depression (34 studies), auditory verbal hallucinations (AVH, 7 studies), negative symptoms in schizophrenia (7 studies), and obsessive-compulsive disorder (OCD, 3 studies). Studies of rTMS versus electroconvulsive treatment (ECT, 6 studies) for depression were meta-analyzed.
Standardized mean effect sizes of rTMS versus sham were computed based on pretreatment-posttreatment comparisons.
The mean weighted effect size of rTMS versus sham for depression was 0.55 (P < .001). Monotherapy with rTMS was more effective than rTMS as adjunctive to antidepressant medication. ECT was superior to rTMS in the treatment of depression (mean weighted effect size -0.47, P = .004). In the treatment of AVH, rTMS was superior to sham treatment, with a mean weighted effect size of 0.54 (P < .001). The mean weighted effect size for rTMS versus sham in the treatment of negative symptoms in schizophrenia was 0.39 (P = .11) and for OCD, 0.15 (P = .52). Side effects were mild, yet more prevalent with high-frequency rTMS at frontal locations.
It is time to provide rTMS as a clinical treatment method for depression, for auditory verbal hallucinations, and possibly for negative symptoms. We do not recommend rTMS for the treatment of OCD.
Direct current (DC) is very effective in modulating spontaneous neuronal firing. The history of electrophysiology starts with the discovery of the biological effects of DC and as early as two centuries ago scalp DC was used to treat mental disorder. Psychophysiological investigations suggested a possible effect of scalp DC in humans. More recently several studies assessed, with motor potentials evoked by transcranial brain stimulation, the motor-cortical excitability changes induced by scalp DC. Even weak DCs pass through the scalp and influence human brain activity. DCs delivered at relatively strong intensities (1 mA) and for long periods (10 min or so), not only influence (either increase or decrease) brain excitability during their application in normal subjects, but induce persistent changes in excitability after their offset that, at least in the motor cortex, can last for almost 1 h. Scalp DC might represent a non-invasive simple and valuable potential treatment for psychiatric and neurologic diseases with changes in brain excitability or focally abnormal (increased or decreased) function.
Three years after the implantation of electrodes in the subthalamic nucleus (STN) and the start of deep brain stimulation (DBS) for advanced Parkinson's disease, a 62-year-old man was admitted because of a stimulation-related manic state that did not respond to treatment with a mood stabiliser and that led to chaotic behaviour, megalomania, serious financial debts and mental incompetence. Although adjustment of the stimulation parameters resulted in a normophoric state with a return of insight and capacity to judge, this was only at the cost of a serious exacerbation of his motor symptoms that left the patient bedridden. There was no therapeutic margin between the two states. Ultimately, there seemed to be only two alternatives: to admit the patient to a nursing home because of serious invalidity, but mentally in good condition, or to admit the patient to a chronic psychiatric ward because of a manic state, but with acceptable motor capacity and ADL functions. Thorough ethical evaluation followed. When not being stimulated, the patient was considered competent to decide about his own treatment; in this condition the patient chose for the second option. In accordance with his own wishes he was therefore legally committed to a chronic ward in the regional psychiatric hospital. The current ethical views on mental competence do not consider the potential influence of modern methods of treatment such as STN-DBS on this capacity.
--Ethical approval of research involving human beings is based on two pillars: supervision of the scientific merit of the research and the risks and burdens for participants by an institutional review board (IRB) or the Dutch Central Committee on Research Involving Human Subjects (CCMO), and obtaining informed consent from the participant or his or her legal guardian. --Discussions on the ethical acceptability of a study generally focus on the first pillar, assessment by an IRB. The second pillar, obtaining informed consent, is often neglected. --Some ethical concepts play a role in obtaining informed consent, especially the concept of the 'therapeutic misconception', i.e. that participating in a study is the same as receiving individualised treatment from a physician. --Of importantance in this matter is the fundamental difference between the research relationship (between investigator and participant) and treatment relationship (between physician and patient). --Understanding the concept of therapeutic misconception is essential to explaining why it is often difficult to obtain valid informed consent from patients for medical research.
For more than a decade high-frequency repetitive transcranial magnetic stimulation (rTMS) has been applied to the left dorsolateral prefrontal cortex (DLPFC) in search of an alternative treatment for depression. The aim of this study was to provide an update on its clinical efficacy by performing a meta-analysis involving double-blind sham-controlled studies.
A literature search was conducted in the databases PubMed and Web of Science in the period between January 1980 and November 2007 with the search terms 'depression' and 'transcranial magnetic stimulation'. Thirty double-blind sham-controlled parallel studies with 1164 patients comparing the percentage change in depression scores from baseline to endpoint of active versus sham treatment were included. A random effects meta-analysis was performed to investigate the clinical efficacy of fast-frequency rTMS over the left DLPFC in depression.
The test for heterogeneity was not significant (QT=30.46, p=0.39). A significant overall weighted mean effect size, d=0.39 [95% confidence interval (CI) 0.25-0.54], for active treatment was observed (z=6.52, p<0.0001). Medication resistance and intensity of rTMS did not play a role in the effect size.
These findings show that high-frequency rTMS over the left DLPFC is superior to sham in the treatment of depression. The effect size is robust and comparable to at least a subset of commercially available antidepressant drug agents. Current limitations and future prospects are discussed.