People with learning disability sometimes display challenging behaviour. This can be managed by use of antipsychotic medication or behavioural therapy or both. There is no solid evidence, however, that these therapies are safe and effective. A randomised controlled trial of antipsychotic medication has been proposed to deliver such evidence. However, this presents difficult issues in the ethics of research with learning disabled people. In particular, is a trial the most efficient and fairest way to evaluate practice in this (...) area? This paper reviews the clinical situation, gives the rationale for the trial, and analyses the ethical arguments for and against such a trial. (shrink)

Behrendt & Young's (B&Y's) novel “unifying model” of hallucinations, although comprehensive, fails to incorporate research into the possible role of 5-HT2A receptors in the mode of action of novel “atypical” antipsychotic drugs (which treat hallucinations effectively), and into the role of such receptors, which are located in thalamocortical circuits, in mediating drug-induced hallucinations.

Assume this hypothetical situation: an American pharmaceutical company, Maxwell Fisch Pharmaceuticals, Inc., wishes to perform clinical trials involving a new antipsychotic medication, Klezac. Klezac is in its third phase of the clinical stage of the drug research process. Once the testing is complete, Maxwell plans to submit a New Drug Application, the official request to begin marketing Klezac, to the Food and Drug Administration. The new drug is expected to receive FDA approval in 2 or more years. The company (...) decides to shift its research and development activities to Z, a small, developing country. In doing so, Maxwell is following the course taken by numerous other drug companies who wish to take advantage of faster governmental approval in foreign sites and ensuing cheaper research costs. (shrink)

Recent years have witnessed an intensification of historical and philosophical research on the link between psychotropic drugs and psychiatric theories. For example, Kendler and Schaffner detailed how the dopamine hypothesis of schizophrenia was intimately linked to the dopamine theory of antipsychotic drug action. Here, a related case is explored: the use of antidepressants' neurochemical effects to speculate about the pathophysiology of depression.This rationale was central to American psychiatrist Schildkraut's landmark article on the catecholamine hypothesis of affective disorders. Accordingly, (...) the paper's hypothesis—that depressions may relate to decreased... (shrink)

Pharmacoresistant schizophrenia is a significant impediment to the successful management of the disease. The expression and function of P‐glycoprotein (P‐gp) has recently been implicated in this phenomenon. P‐gp is a multidrug efflux transporter that prevents drug substrates from crossing the blood–brain barrier (BBB). Although the direct interaction between individual antipsychotic agents and P‐gp has been demonstrated, the effect of antipsychotic drug combinations used in disease management on P‐gp transport function remains to be elucidated. This could have important clinical (...) implications in some individuals as dosage adjustments based on plasma drug concentration changes may not always be appropriate if drug–drug interactions and the resulting changes in drug concentration in the brain are not considered. This paper introduces the potential impact that combination antipsychotic therapy may have on P‐gp function at the BBB and discusses the consequences of this in the prevention and circumvention of unfavourable therapeutic response in schizophrenic disorders. BioEssays 30:183–188, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In psychiatry, pharmacological drugs play an important experimental role in attempts to identify the neurobiological causes of mental disorders. Besides being developed in applied contexts as potential treatments for patients with mental disorders, pharmacological drugs play a crucial role in research contexts as experimental instruments that facilitate the formulation and revision of neurobiological theories of psychopathology. This paper examines the various epistemic functions that pharmacological drugs serve in the discovery, refinement, testing, and elaboration of neurobiological theories of (...) mental disorders. I articulate this thesis with reference to the history of antipsychotic drugs and the evolution of the dopamine hypothesis of schizophrenia in the second half of the twentieth century. I argue that interventions with psychiatric patients through the medium of antipsychotic drugs provide researchers with information and evidence about the neurobiological causes of schizophrenia. This analysis highlights the importance of pharmacological drugs as research tools in the generation of psychiatric knowledge and the dynamic relationship between practical and theoretical contexts in psychiatry. (shrink)

Usage of psychotropics during pregnancy and lactation has always been a topic of debate and controversy. The debate stems from the potential adverse effects on the growing fetus or infants due to the transfer of psychotropic drugs through placenta or breast milk of mothers receiving them; and the problem of discontinuing psychotropics in lactating mother considering chances of relapse. However, most of the psychotropics are found to be relatively safe when used cautiously during the lactation phase. This article describes (...) available data on the use of psychotropics in lactating mothers, in particular, in relation to the safety profile of infants. (shrink)

Children who experience well-being are engaging more confidently and positively with their caregiver and peers, which helps them to profit more from available learning opportunities and support current and later life outcomes. The goodness-of-fit theory suggests that children’s well-being might be a result of the interplay between their temperament and the environment. However, there is a lack of studies that examined the association between children’s temperament and well-being in early childhood education and care, and whether this association is affected by (...) ECEC process quality. Using a multilevel random coefficient approach, this study examines the association between toddlers’ temperament and well-being in Norwegian ECEC and investigates whether process quality moderates this association. Results reveal an association between temperament and well-being. Staff-child conflict moderates the association between shyness and well-being, and between activity and well-being. Moreover, high emotional behavioral support moderates the association between activity and well-being. Extra attention should be paid by the staff to these children’s needs. (shrink)

In The Ethics of Food, Gregory E. Pence brings together a collection of voices who share the view that the ethics of genetically modified food is among the most pressing societal questions of our time. This comprehensive collection addresses a broad range of subjects, including the meaning of food, moral analyses of vegetarianism and starvation, the safety and environmental risks of genetically modified food, issues of global food politics and the food industry, and the relationships among food, evolution, and human (...) history. (shrink)

Schizophrenia is a serious mental illness characterized by a disconnection between brain regions. Transcranial magnetic stimulation is a non-invasive brain intervention technique that can be used as a new and safe treatment option for patients with schizophrenia with drug-refractory symptoms, such as negative symptoms and cognitive impairment. However, the therapeutic effects of transcranial magnetic stimulation remain unclear and would be investigated using non-invasive tools, such as functional connectivity. A longitudinal design was adopted to investigate the alteration in FC dynamics using (...) a dynamic functional connectivity approach in patients with schizophrenia following high-frequency repeated transcranial magnetic stimulation with the target at the left dorsolateral prefrontal cortex. Two groups of schizophrenia inpatients were recruited. One group received a 4-week high-frequency rTMS together with antipsychotic drugs, while the other group only received antipsychotic drugs. Resting-state functional magnetic resonance imaging and psychiatric symptoms were obtained from the patients with schizophrenia twice at baseline and after 4-week treatment. The dynamics was evaluated using voxel- and region-wise FC temporal variability resulting from fMRI data. The pattern classification technique was used to verify the clinical application value of FC temporal variability. For the voxel-wise FC temporary variability, the repeated measures ANCOVA analysis showed significant treatment × time interaction effects on the FC temporary variability between the left DLPFC and several regions, including the thalamus, cerebellum, precuneus, and precentral gyrus, which are mainly located within the cortico-thalamo-cerebellar circuit. For the ROI-wise FC temporary variability, our results found a significant interaction effect on the FC among CTCC. rTMS intervention led to a reduced FC temporary variability. In addition, higher alteration in FC temporal variability between left DLPFC and right posterior parietal thalamus predicted a higher remission ratio of negative symptom scores, indicating that the decrease of FC temporal variability between the brain regions was associated with the remission of schizophrenia severity. The support vector regression results suggested that the baseline pattern of FC temporary variability between the regions in CTCC could predict the efficacy of high-frequency rTMS intervention on negative symptoms in schizophrenia. These findings confirm the potential relationship between the reduction in whole-brain functional dynamics induced by high-frequency rTMS and the improvement in psychiatric scores, suggesting that high-frequency rTMS affects psychiatric symptoms by coordinating the heterogeneity of activity between the brain regions. Future studies would examine the clinical utility of using functional dynamics patterns between specific brain regions as a biomarker to predict the treatment response of high-frequency rTMS. (shrink)

On June 16, 2003, the Supreme Court ruled that forced administration of antipsychotic drugs to a defendant facing serious criminal charges is appropriate in order to render that defendant competent to stand trial, but only in limited circumstances. The treatment must be medically appropriate, substantially unlikely to have side effects that may undermine the fairness of the trial, and necessary to significantly further important government interests, after taking account of less-intrusive alternatives.Charles Sell, a former dentist, had a long (...) history of mental illness. He had been hospitalized twice, in 1982 and 1984, after expressing paranoid ideas to law enforcement officials. In May 1997, Sell was charged with fifty-six counts of mail fraud, six counts of Medicaid fraud, and one count of money laundering. He was released on bail after a magistrate determined that he was currently competent to stand trial. (shrink)

On June 16, 2003, the Supreme Court ruled that forced administration of antipsychotic drugs to a defendant facing serious criminal charges is appropriate in order to render that defendant competent to stand trial, but only in limited circumstances. The treatment must be medically appropriate, substantially unlikely to have side effects that may undermine the fairness of the trial, and necessary to significantly further important government interests, after taking account of less-intrusive alternatives.Charles Sell, a former dentist, had a long (...) history of mental illness. He had been hospitalized twice, in 1982 and 1984, after expressing paranoid ideas to law enforcement officials. In May 1997, Sell was charged with fifty-six counts of mail fraud, six counts of Medicaid fraud, and one count of money laundering. He was released on bail after a magistrate determined that he was currently competent to stand trial. (shrink)

Most studies are inclined to report positive rather than negative or inconclusive results. It is currently unknown how clinicians appraise the results of a randomized clinical trial. For example, how does the study funding source influence the appraisal of an RCT, and do positive findings influence perceived credibility and clinical relevance? This study investigates whether psychiatrists’ appraisal of a scientific abstract is influenced by industry funding disclosures and a positive outcome. Dutch psychiatrists were randomized to evaluate a scientific abstract describing (...) a fictitious RCT for a novel antipsychotic drug. Four different abstracts were created reporting either absence or presence of industry funding disclosure as well as a positive or a negative outcome. Primary outcomes were the perceived credibility and clinical relevance of the study results. Secondary outcomes were the assessment of methodological quality and interest in reading the full article. Three hundred ninety-five psychiatrists completed the survey. Industry funding disclosure was found not to influence perceived credibility nor interpretation of its clinical relevance. A negative outcome was perceived as more credible than a positive outcome 0.43 to 1.18, p?), but did not affect clinical relevance scores. In this study, industry funding disclosure was not associated with the perceived credibility nor judgement of clinical relevance of a fictional RCT by psychiatrists. Positive study outcomes were found to be less credible compared to negative outcomes, but industry funding had no significant effects. Psychiatrists may underestimate the influence of funding sources on research results. The fact that physicians indicated negative outcomes to be more credible may point to more awareness of existing publication bias in the scientific literature. (shrink)

Rare copy number variants have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large CNVs at several loci, including microdeletions at 1q21.1, 3q29, 15q13.3 and 22q11.2 and microduplication at 16p11.2. However, these CNVs collectively account for a small fraction of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy (...) number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 patients versus 2 of 7,431 controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. © 2011 Macmillan Publishers Limited. All rights reserved. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 11.4 (2001) 391-400 [Access article in PDF] Bioethics Inside the Beltway A Shooting on Capitol Hill: "The Ruby Satellite System," Mental Illness, and Failure of the American Legal System Peter J. Cohen On 24 July 1998, Russell Eugene Weston, Jr., stormed the United States Capitol, forced his way through a security checkpoint, bypassed a metal detector, and entered the office complex of Representative Tom (...) DeLay (R-TX), the House Majority Whip (Weil 1998). During this period of terror, he shot and killed two officers of the Capitol Police and seriously wounded another as they attempted to end his foray. 1 Weston was severely wounded by several Capital police officers and taken into custody. After being treated for his injuries, he was incarcerated in the District of Columbia. 2On 5 May 1999, Weston was transferred to the Federal Correctional Institute in Butner, North Carolina (United States v. Weston, 69 F. Supp. 2d 99 (D.D.C. 1999), 103), where he remains to this day. He has neither been brought to trial nor received appropriate psychiatric therapy, but continues to be warehoused "in solitary confinement under constant observation... in a psychotic state (United States v. Weston, 255 F.3d 873; LEXIS 16851 (U.S. App. 2001b), 3-4 [LEXIS]). I will briefly detail the legal events responsible for this mad situation and suggest alternative actions that should have been taken at the very onset of the case. Early Chronology Although overtly the crime appeared to be senseless and without any conceivable motivation, Weston believed that his acts were justified and necessary. The story he told to the court-appointed forensic psychiatrist, Sally C. Johnson, M.D., 3 was that while working for NASA in the early 1980s, he had developed a "Ruby Satellite System," a powerful machine that could reverse time. With access to this system, nothing was permanent--the user could simply reverse time and exit from the current scene. However, the "System" was now controlled by cannibals who were developing and spreading "Black Heva," the deadliest disease known to [End Page 391] humankind, similar to HIV or the plague. It resulted from human corpses rotting and turning black. Time was running out, and Weston believed he had to return to override the "Ruby Satellite System" in the Capitol so that he could stem the spread of "Black Heva" and prevent world calamity. He believed that if he were tried, convicted, and even executed, he could simply time reverse himself, place himself in a safe within the Capitol, and subsequently resume his life at whatever point he chose (United States v. Weston, 206 F.3d 9 (D.C. Cir. 2000), 19-20).On 22 April 1999, the district court accepted Dr. Johnson's diagnosis that Weston suffered from paranoid schizophrenia, the symptoms of which were so severe that he would be incapable of understanding the proceedings against him and of assisting in his own defense. On this basis, the court had no difficulty in finding him incompetent to stand trial (U.S. v. Weston 1999, 102).At Weston's initial hearing, Dr. Johnson had testified that medication would be efficacious in treating Weston's delusions: [T]he standard of care in someone suffering from this type of symptom picture would be to treat them with medication.... [T]here is a good likelihood that he'll have a positive response, positive in the sense that his symptoms will diminish in response to treatment.... The potential benefits to treating the defendant far outweigh the risks.... (U.S. v. Weston 1999, 108) The defense presented no expert testimony refuting Dr. Johnson's presentation. The district court then ordered that Weston begin receiving medication in order to render him nondangerous and competent for trial (U.S. v. Weston 1999, 108-9). The Problem Weston refused to be medicated! 4 He has continued to claim that the administration of antipsychotic drugs against his will would violate his Fifth Amendment due process liberty interest in avoiding unwanted bodily intrusion and implicated... (shrink)

Antipsychotic medications are sometimes imposed on psychiatric patients deemed dangerous to themselves and others. This is based on the assumption that treatment is safe and effective, and that recovery depends on biological adjustment. Under new laws, patients can be required to remain on these medications after leaving hospitals. However, survivors attest that forced treatment used as a restraint can feel like torture, while the consequences of withdrawal can also be severe.

ABSTRACT: Abilify MyCite was granted regulatory approval in 2017, becoming the world’s first “smart pill” that could digitally track whether patients had taken their medication. The new technology was introduced as one that had gained the support of patients and ethicists alike, and could contribute to solving the widespread and costly problem of patient nonadherence. Here, we offer an in-depth exploration of this narrative, through an examination of the origins and development of Abilify, the drug that would later become MyCite. (...) This history illuminates how an antipsychotic can become a top-selling drug and maintain its blockbuster status for more than a decade. It also provides a detailed case study for how knowledge is constructed within the logic of biomedical capitalism, providing impetus to reexamine claims regarding how MyCite addresses patient nonadherence, engenders patient support, and is ethicist-approved. (shrink)

In recent years, a debate has emerged on whether bodily sensations are typically accompanied by a sense of body ownership, namely a distinctive experience of one's body or body part as one's own. Realists about the sense of body ownership heavily rely on evidence from experimentally-induced bodily illusions (e.g., the rubber hand illusion) and pathological disownership syndromes (e.g. somatoparaphrenia). In this chapter, I will introduce novel evidence regarding body disownership syndromes induced by psychoactive drugs rather than pathological conditions, and (...) discuss its relevance to the debate on the sense of body ownership. (shrink)

Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a “necessary” prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of “drug instrumentalization.” Psychoactive drugs are consumed for their effects on mental states. Humans are able (...) to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific “instrumentalization goals” and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future. (shrink)

Few data exist regarding treatment with antipsychotics in forensic psychiatric patient populations with high social dangerousness. We performed a secondary analysis of 681 patients treated with at least one antipsychotic, extracted from a 1-year observational retrospective study, conducted on 730 patients treated in the Italian Residencies for Execution of Security Measures. We aimed at investigating antipsychotic polypharmacy and high dose/very high-dose antipsychotics, as well as the possible factors associated with such therapeutic regimens. High dose/very high-dose antipsychotics were defined (...) as a prescribed daily dose to WHO-defined daily dose ratio greater than 1.5 or 3.0, respectively. Binary logistic regression analysis was used in three models to test possible predictors of antipsychotic polypharmacy, high-dose antipsychotics, and very high-dose antipsychotic prescription. Antipsychotic polypharmacy resulted in n = 308 of the patients, n = 346 received high-dose antipsychotics, and n = 96 very high-dose antipsychotics. The multivariate analysis disclosed an association between antipsychotic polypharmacy and male gender : 2.75 and 95% CI: 1.34–5.65), long-acting injectable antipsychotic prescription, and aggressive behavior in REMS. High-dose antipsychotics were also associated with male gender, LAI antipsychotic prescription, and aggressive behavior in REMS. The use of antipsychotic polypharmacy and high-dose antipsychotics is frequent in the REMS population. These results might depend on regulatory and organizational aspects of the REMS system, including variability in structures, lack of a common model of care, and lack of stratified therapeutic security. (shrink)

People with dementia at times exhibit threatening and physically aggressive behavior toward care staff in residential aged care facilities (RACFs). Current clinical guidelines recommend judicious use of antipsychotic (AP) medications when there is an immediate risk of harm to care staff in RACFs and non-pharmacological interventions have failed to avert the threats. This article examines an account of how this recommendation can be ethically defensible: caregivers in RACFs may have a prima facie ethical justification, in certain cases, to use (...) APs as an act of self-defense. The author examines whether such uses of APs meet the three commonly invoked conditions of ethically permissible acts of self-defense—namely, the conditions of liability, proportionality, and necessity—and argues that such conditions obtain only in a restricted range of cases. The liability constraint can be satisfied if residents are the only ones who are causally responsible for the threats they pose. Further, the condition of proportionality obtains if there is sufficient objective ground to demonstrate that the harm of using the medications does not outweigh the good to be secured. Lastly, the necessity condition obtains when the medications are used at their lowest effective dosage and caregivers in RACFs can reasonably assume that, for the purpose of averting threats posed by residents, the use of APs is the only available course of action. Not meeting any of these fairly stringent conditions renders uses of APs as acts of self-defense in RACFs morally impermissible actions. -/- . (shrink)

Philosophical and empirical research on bodily awareness has mostly focused so far on bodily disorders – such as anorexia nervosa, somatoparaphrenia, or xenomelia (body integrity dysphoria) – and bodily illusions induced in an experimental setting – such as the rubber hand illusion, or the thermal grid illusion. Studying these conditions can be illuminating to investigate a broad range of issues about the nature, function, and etiology of bodily experience. However, a number of psychoactive compounds can also induce a remarkably wide (...) variety of bodily effects that have received little attention despite their relevance to these issues. Some of these effects are similar to those associated with bodily disorders or experimental bodily illusions, while others appear to be unique. The purpose of this chapter is to provide an overview of these lesser known bodily effects of psychoactive compounds, and outline some ways in which they can bear on recent debates regarding bodily awareness and bodily ownership. (shrink)

Objectives: The aim of this study was to investigate the actual condition of the students of University of Rajshahi (RU) regarding drug abuse and addiction. Using case study method the research was conducted with four objectives: (a) to find out how respondents began drug abuse; (b) to discover the causes of their drug addiction; (c) to understand the process of their drug abuse; and (d) to find out the economic, social and health effects of drug abuse. Methods: Case study method (...) was used in this research. Through snowball sampling 18 drug- addicted students of RU were selected as respondents. In-depth interview with a schedule was used to collect data from the respondents in January 2019. Results: Findings of the study show that the causes of drug addiction included curiosity, frustration, friends’ request, neglect from family and friends etc. The drugs which they usually abused were Yaba, Phensydyle, Ganja (Weed), Chuani etc. Their average monthly expenditure for collecting drugs was in between Taka 8,000-10,000. They collected those drugs from rickshaw pullers at different points within the campus and from Mizaner Mor, Budhpara slum and other places outside the campus. The respondents opined that drugs were available if sufficient money could be spent. The respondents had senior and junior fellow students and local boys as companions while taking drugs. Most of them faced physical problems after taking drugs, and some of them tried to get rid of this curse of drug addiction. Conclusion: The findings of this research show that the rate of drug addiction among the students of RU was quite alarming. Therefore, all stakeholders including the students, guardians, teachers, university authority, the law makers and law enforcing agencies, researchers, civil society, NGO’s and the state must come forward together to combat this formidable foe. (shrink)

Drug exceptional access programs (DEAPs) exist across Canada to address gaps in access to pharmaceuticals. These programs circumvent standard procedures, raising epistemic, economic, social and political issues. This commentary provides insights into these issues by revealing the context and procedures on which these programs depend.

The “hijacking” and “drug instrumentalization” models of psychoactive drug use predict opposite outcomes in terms of adaptive behavior and fitness benefits. Which is the range of applicability of each model? To answer this question, we need more data than those reported by studies focusing on medical, psychiatric, and legal problems in addicted users. An evolutionary analysis requires a much wider focus.

Studies have shown that both serotonin and glutamate receptor systems play a crucial role in the mechanisms underlying drug-induced synesthesia. The specific nature of these mechanisms, however, continues to remain elusive. Here we propose two distinct hypotheses for how synesthesia triggered by hallucinogens in the serotonin-agonist family may occur. One hypothesis is that the drug-induced destabilization of thalamic projections via GABAergic neuronal circuits from sensory areas leads to a disruption of low-level, spontaneous integration of multisensory stimuli. This sort of integration (...) regularly occurs when spatial and temporal attributes match. Destabilization of feedback loops, however, can result in incongruent experiences or binding of random thalamus activation with sensory input in a particular sensory modality. The second hypothesis builds on embodied cognition, cases in which visual images of external stimuli activate task-related neural regions. On this proposal, binding processes that do not normally generate awareness become accessible to consciousness as a result of decreased attentional discrimination among incoming stimuli. (shrink)

Science has needed a dispassionate valuation of psychoactive drugs, but a motivational analysis should be conducted with respect to long-term reward rather than reproductive fitness. Because of hyperbolic overvaluation of short-term rewards, an individual's valuation depends on the time she forms it and the times she will revisit it, sometimes making her best long-term interest lie in total abstinence.

BackgroundAntipsychotic-induced weight gain is a contributing factor in the reduced life expectancy reported amongst people with psychotic disorders. CYP2D6 is a liver enzyme involved in the metabolism of many commonly used antipsychotic medications. We investigated if CYP2D6 genetic variation influenced weight or BMI among people taking antipsychotic treatment.MethodsWe conducted a systematic review and a random effects meta-analysis of publications in Pubmed, Embase, PsychInfo, and CENTRAAL that had BMI and/or weight measurements of patients on long-term antipsychotics by their CYP2D6-defined (...) metabolic groups.ResultsTwelve studies were included in the systematic review. All cohort studies suggested that the presence of reduced-function or non-functional alleles for CYP2D6 was associated with greater antipsychotic-induced weight gain, whereas most cross-sectional studies did not find any significant associations. Seventeen studies were included in the meta-analysis with clinical data of 2,041 patients, including 93 poor metabolizers, 633 intermediate metabolizers, 1,272 normal metabolizers, and 30 UMs. Overall, we did not find associations in any of the comparisons made. The estimated pooled standardized differences for the following comparisons were PM versus NM; weight = –0.07, BMI = 0.40. IM versus NM; weight = 0.09 and BMI = 0.09. UM versus EM; weight = 0.01 and BMI = –0.08.ConclusionOur systematic review of cohort studies suggested that CYP2D6 poor metabolizers have higher BMI than normal metabolizers, but the data of cross-sectional studies and the meta-analysis did not show this association. Although our review and meta-analysis constitutes one of the largest studies with comprehensively genotyped samples, the literature is still limited by small numbers of participants with genetic variants resulting in poor or UMs status. We need further studies with larger numbers of extreme metabolizers to establish its clinical utility in antipsychotic treatment. CYP2D6 is a key gene for personalized prescribing in mental health. (shrink)

Despite their centrality to medicine, drugs are not easily defined. We introduce two desiderata for a basic definition of medical drugs. It should: (a) capture everything considered to be a drug in medical contexts and (b) rule out anything that is not considered to be a drug. After canvassing a range of options, we find that no single definition of drugs can satisfy both desiderata. We conclude with three responses to our exploration of the drug concept: maintain (...) a monistic concept, or choose one of two pluralistic outcomes. Notably, the distinction between drugs and other substances is placed under pressure by the most plausible of the options available. (shrink)

We often get evidence concerning the reliability of our own thinking about some particular matter. This “higher-order evidence” can come from the disagreement of others, or from information about our being subject to the effects of drugs, fatigue, emotional ties, implicit biases, etc. This paper examines some pros and cons of two fairly general models for accommodating higher-order evidence. The one that currently seems most promising also turns out to have the consequence that epistemic akrasia should occur more frequently (...) than is sometimes supposed. But it also helps us see why this might not be a bad thing. (shrink)

Periodic and unexpected shortages of drugs, biologics, and even medical devices have become commonplace in the United States. When shortages occur, hospitals and clinics need to decide how to ration their available stock. When such situations arise, institutions can choose from several different allocation schemes, such as first-come, first-served, a lottery, or a more rational and calculated approach. While the first two approaches sound reasonable at first glance, there are a number of problems associated with them, including the inability (...) to make fine, individual patient-centered decisions. They also do not discriminate between what kinds of patients and what types of uses may be more deserving or reasonable than others. In this article I outline an ethically acceptable procedure for rationing drugs during a shortage in which demand outstrips supply. (shrink)

Background: Giving money as a direct incentive for patients in exchange for depot medication has proved beneficial in some clinical cases in assertive outreach . However, ethical concerns around this practice have been raised, and will be analysed in more detail here.Method: Ethical concern voiced in a survey of all AO teams in England were analysed regarding their content. These were grouped into categories.Results: 53 of 70 team managers mentioned concerns, many of them serious and expressing a negative attitude towards (...) giving money for depot adherence. Four broad categories of ethical concern following Christensen’s concept were distinguished: valid consent and refusal , psychiatric paternalism , resource allocation , organisational relationships , with a residual category others and unspecified .Discussion: The main concerns identified are discussed on the background of existing ethical theories in healthcare and the specific problems of community mental health and AO. Points for practice are derived from this discussion. A way forward is outlined that includes informed consent and an operational policy in the use of incentives, further randomised controlled trials and qualitative studies, and continuing discussions with all stakeholders, especially service users. (shrink)

Intensive research is carried out to develop a disease-modifying drug for Alzheimer’s disease. The development of drug candidates that reduce Aß or tau in the brain seems particularly promising. However, these drugs target people at risk for AD, who must be identified before they have any, or only moderate, symptoms associated with the disease. There are different strategies that may be used to identify these individuals. Each of these strategies raises different ethical challenges. In this paper, we analyse these (...) challenges in relation to the risk stratification for AD necessary for using these drugs. We conclude that the new drugs must generate large health benefits for people at risk of developing AD to justify the ethical costs associated with current risk stratification methods, benefits much larger than current drug candidates have. This conclusion raises a new set of ethical questions that should be further discussed. No data are available. (shrink)

Each of the antiretroviral drugs that are currently used to stop the progression of HIV infection causes its own specific side effects. Despite the expansion, multiplication, and simplification of treatment options over the past decade, side effects continue to affect people living with HIV. Yet, we see a clear disconnect between the way side effects are normalized, routinized, and framed in clinical practice and the way they are experienced by people living with HIV. This paper builds on the premise (...) that new approaches are needed to understand side effects in a manner that is more reflective of the subjective accounts of people living with HIV. Drawing on the work of Deleuze and Guattari, it offers an original application of the theory of ‘assemblage’. This theory offers a new way of theorizing side effects, and ultimately the relationship between the body and antiretroviral drugs (as technologies). Combining theory with examples derived from empirical data, we examine the multiple ways in which the body connects not only to the drugs but also to people, things, and systems. Our objective is to illustrate how this theory dares us to think differently about side effects and allows us to originally (re)think the experience of taking antiretroviral drugs. (shrink)