Merlin Bittlinger

Dealing With Side Effects of Deep Brain Stimulation: Lessons Learned From Stimulating the STN

Deep brain stimulation (DBS) is increasingly investigated as a therapy for psychiatric disorders. In the ethical evaluation of this novel approach, incidence and impact of side effects (SE) play a key role. In our contribution, we analyze the discussion on SE of DBS of the subthalamic nucleus (STN)—a standard therapy for movement disorders like Parkinsons disease (PD)—based on 66 case reports, 69 review papers, and 347 outcome studies from 1993 to 2009. We show how the DBS community increasingly acknowledged the complexity of STN-DBS side effects. Then we discuss the issue of study quality and the methods used to assess SE. We note that some side effects are the subject of conflicting evaluations by the different stakeholders involved. This complicates the ethical controversy inherent in any novel treatments for diseases that involve psychiatric aspects. We delineate how the lessons from STN-DBS could guide future DBS applications in the field of psychiatry.

Ethical Focal Points in the International Practice of Deep Brain Stimulation

Deep brain stimulation (DBS) is a standard therapy for several movement disorders, and the list of further indications that are investigated is growing rapidly. We performed two surveys among DBS experts (n1 = 113) and centers (n2 = 135) to identify ethical focal points in the current global practice of DBS. The data indicate a mismatch between the patients’ fears and the frequencies of the suspected side effects, a significant “satisfaction gap,” signs of improvements of outcome, habituation effects in terms of involved disciplines, a growing spectrum of novel indications that partly conflicts with the experts’ success probability ratings, and differences in the density of supply between countries that might affect the future development of DBS. We formulate ethical recommendations with regard both to patient-related practices (e.g., recruitment, assurance of alternatives) and to institutional development (e.g., measures for quality assurance and for the development of novel DBS indications).

Ethical considerations for deep brain stimulation trials in patients with early-onset Alzheimer’s disease

Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimers disease, with several recruiting participants <65 and thus have early-onset Alzheimers disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression. These considerations include appropriate patient selection and signing of an informed consent for genetic testing; appropriate study design; potential outcomes that people with EOAD could expect; and accurate interpretation and balanced discussion of trial results. Finally, recommendations for future DBS for AD trials will be made to ensure that EOAD patients will not experience avoidable harms should they be enrolled in these experimental studies.

The Patient's Voice in DBS Research: Advancing the Discussion through Methodological Rigor

Listening to the patient is essential for neuroethics. To preempt the accusation of ethical paternalism, discussions of deep brain stimulation (DBS) research should not talk about the patients’ exp...

The re-emergence of psychiatric neurosurgery: insights from a cross-national study of newspaper and magazine coverage

BackgroundSurgical approaches to treat psychiatric disorders have made a comeback. News media plays an essential role in exposing the public to trends in health care such as the re-emergence of therapeutic interventions in psychiatric neurosurgery that were set aside for decades, and in shaping attitudes and acceptance to them.MethodWe conducted an analysis of media articles covering all types of psychiatric neurosurgery published in Canada, USA, Germany, and Spain between the years 1960 and 2015. We applied both quantitative and qualitative methods to elucidate patterns of reporting for conditions, themes and tone, across geographic regions, time, and for type of intervention.ResultsCoverage of psychiatric neurosurgery has surged since 2001 and is largely consistent across the countries examined. It focuses on depression and deep brain stimulation, and is explicit about historical context. The tone of coverage becomes more positive for Canada, USA and Spain over time; the tone of coverage from Germany remains cautious. Identity and privacy are among the few ethical and philosophical issues raised, notably in the German press.ConclusionsThe focused and optimistic attention to contemporary psychiatric neurosurgery in the media, but inattention to ethical issues, places an extra burden on functional neurosurgeons, psychiatrists, and other frontline health professionals to attend to queries from patients and policy makers about the full range of relevant emergent and emerging interventions and the mental health issues to which they may beneficially apply.

Opening the debate on deep brain stimulation for Alzheimer disease – a critical evaluation of rationale, shortcomings, and ethical justification

BackgroundDeep brain stimulation (DBS) as investigational intervention for symptomatic relief from Alzheimer disease (AD) has generated big expectations. Our aim is to discuss the ethical justification of this research agenda by examining the underlying research rationale as well as potential methodological pitfalls. The shortcomings we address are of high ethical importance because only scientifically valid research has the potential to be ethical.MethodWe performed a systematic search on MEDLINE and EMBASE. We included 166 publications about DBS for AD into the analysis of research rationale, risks and ethical aspects. Fifty-eight patients were reported in peer-reviewed journals with very mixed results. A grey literature search revealed hints for 75 yet to be published, potentially enrolled patients.ResultsThe results of our systematic review indicate methodological shortcomings in the literature that are both scientific and ethical in nature. According to our analysis, research with human subjects was performed before decisive preclinical research was published examining the specific research question at stake. We also raise the concern that conclusions on the potential safety and efficacy have been reported in the literature that seem premature given the design of the feasibility studies from which they were drawn. In addition, some publications report that DBS for AD was performed without written informed consent from some patients, but from surrogates only. Furthermore, registered ongoing trials plan to enroll severely demented patients. We provide reasons that this would violate Art. 28 of the Declaration of Helsinki, because DBS for AD involves more than minimal risks and burdens, and because its efficacy and safety are not yet empirically established to be likely.ConclusionBased on our empirical analysis, we argue that clinical research on interventions of risk class III (Food and Drug Administration and European Medicines Agency) should not be exploratory but grounded on sound, preclinically tested, and disease-specific a posteriori hypotheses. This also applies to DBS for dementia as long as therapeutic benefits are uncertain, and especially when research subjects with cognitive deficits are involved, who may foreseeably progress to full incapacity to provide informed consent during the required follow-up period.