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)

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)

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)

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)

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.

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)

Residents with dementia in long-term care facilities (LTCFs) often receive antipsychotic (AP) medications without clear clinical indications. One non-clinical factor influencing the use of APs in LTCFs is low staff levels. Often, using APs is viewed and rationalised by healthcare professionals in LTCFs as a lesser evil option to manage low staff levels. This paper investigates the ethical plausibility of using APs as a lesser of two evils in resource-constrained LTCFs. I examine the practice vis-à-vis the three frequently invoked conditions (...) of lesser evil justifications as specified in the wider philosophical literature. These conditions include (1) the necessity condition, (2) the condition of sensitivity to both deontic (ie, constraint-based) and non-deontic (ie, outcome-based) considerations and (3) the commensurability condition. I argue that there are considerable difficulties in demonstrating that the practice in question satisfies the conditions of lesser evil justifications. In particular, there are major difficulties in satisfying the condition of sensitivity to deontic and outcome-based considerations, and the commensurability condition. I also argue that the current philosophical debate on lesser-evil justifications is not straightforwardly applicable to the practice of using APs for non-clinical purposes in LTCFs. I contend that caregivers are not so-called ‘generic’ agents, and the assumed rarity of lesser evil cases is questionable. I conclude that until further work is done to resolve these issues, the lesser evil reasoning cannot be, at least routinely, used to formulate robust moral justifications for the practice in question. (shrink)

A 38-year-old army officer started therapy in 2020 with a four-year history of auditory hallucinations and delusions of reference, persecution and grandeur, symptoms that were resistant to traditional antipsychotic medications. He follows an integrative psychotherapy program that aims to reduce his anxiety, continues his antipsychotic medications, and has Infra-Low Frequency Neurofeedback. After his initial assessment he had a 40 min session of Infra-Low Frequency Neurofeedback before any other kind of intervention. Before and immediately after the session he completed the SCL-90 (...) scale and the Visual Analog Scale covering 20 aspects of his psychological and physical state as well as his schizophrenic symptoms. This first Neurofeedback session had dramatic effects on his psychotic symptoms, levels of anxiety and psychosomatic condition, before his first psychotherapy session and/or any changes in his antipsychotic medication. The above results have great importance due to the severity and chronicity of schizophrenia. Informed consent was obtained from the participant for the publication of this case report (including all data and images). (shrink)

The analysis presented in this article reveals an ambiguity and tension in human rights theory concerning the delusional person’s freedom of belief and thought. Firstly, it would appear that the concepts ‘opinion’ and ‘thought’ are defined in human rights discussion in such a way that they do include delusions. Secondly, the internal freedom to hold opinions and thoughts is defined in human rights discussion and international human rights covenants as an absolute human right which should not be restricted in any (...) situation for any reason. These views, if understood literally, imply that a person has an absolute right to hold a delusion. However, this kind of conclusion has not been made in mental health laws, the ethical principles guiding psychiatric care or the practice of psychiatry. Instead, they assume that the use of involuntary antipsychotic medication is justified even thought its purpose is to influence delusions. The ambiguity and tension in human rights theory concerning the freedom of belief and thought challenge us to develop this theory within an interdisciplinary discussion so that people with delusions are taken into account properly. (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.

BackgroundAt present, adherence to antipsychotic treatment is often poor, leading to the recurrence of symptoms. This increases the likelihood of the patient experiencing disability and thus increases the disease burden for the patient, their family, and society as a whole. However, to date, there is no clear evidence regarding the effect of medication adherence interventions on outcomes for patients with schizophrenia. Moreover, the traditional intervention methods are limited by manpower and resources in low- and middle-income countries. Recent studies have demonstrated (...) that increasing a patient’s level of self-compassion may improve their treatment adherence. Online mental health care interventions have advantages in terms of feasibility and acceptability for patients with schizophrenia. In this regard, a WeChat-based self-compassion training protocol to improve patient treatment adherence was designed in this study and will be evaluated in the future to determine its impact on patients with schizophrenia.MethodsThe protocol for the randomized controlled trial is based on the SPIRIT 2013 statement. This parallel RCT will aim to recruit 392 patients with schizophrenia who will be randomized at a 1:1 ratio into a 3-week intervention or control group. Both groups will receive routine care. The intervention group will also receive WeChat-based self-compassion training, which requires participants to complete three tasks every day, including a reading task, a meditation task, and a self-compassion journal task. The control group will receive WeChat-based psychological health education, which will only require participants to read positive articles about psychological health every day. Medication adherence, self-compassion, stigma, and social support will be measured at baseline, immediately after the intervention, and 3 weeks after the intervention. Program feasibility will be evaluated throughout the course of the study, and acceptability will be measured immediately after the intervention.Expected results:The intervention described here will address the barriers to accessing mental health care for people with schizophrenia, including patients’ desire for independent management, difficulty accessing providers, and concerns about privacy and stigma. The current study provides guidance for clinical nurses to carry out psychological intervention, with the ultimate aim of addressing the problems associated with a shortage of psychological professionals in low- and middle-income countries. (shrink)

The discovery of antipsychotics and anti-depressants occurred when psychodynamic and phenomenological–anthropological approaches prevailed in psychiatry. Roland Kuhn personified that time as being one of the founders of Daseinsanalyse and also the discoverer of imipramine. Influenced by Binswanger and Scheler, Kuhn worked with the concept of “vital depressive disposition,” while emphasizing the preeminence of psychopathology over statistic methods. Consequently, he could not be satisfied with what he foresaw as “clouds of a coming disaster”:Since that time, there has been a worldwide (...) use of surveys, whose results are “exactly” tabulated with numbers, statistically evaluated, and represented in tables.... (shrink)

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)

For years, phenomenological psychiatry has proposed that distortions of the temporal structure of consciousness contribute to the abnormal experiences described before schizophrenia emerges, and may relate to basic disturbances in consciousness of the self. However, considering that temporality refers mainly to an implicit aspect of our relationship with the world, disturbances in the temporal structure of consciousness remain difficult to access. Nonetheless, previous studies have shown a correlation between self disorders and the automatic ability to expect an event in time, (...) suggesting timing is a key issue for the psychopathology of schizophrenia. Timing disorders may represent a target for cognitive remediation, but this requires that disorders can be demonstrated at an individual level. Since cognitive impairments in patients with schizophrenia are discrete, and there is no standardized timing exploration, we focused on timing impairments suggested to be related to self disorders. We present the case report of AF, a 22 year old man suffering from schizophrenia, with no antipsychotic intake. Although AF shows few positive and negative symptoms and has a normal neurocognitive assessment, he shows a high level of disturbance of Minimal Self Disorders (SDs) (assessed with the EASE scale). Moreover, AF has a rare ability to describe his self and time difficulties. An objective assessment of timing ability (variable foreperiod task) confirmed that AF had temporal impairments similar to those previously described in patients, i.e., a preserved ability to distinguish time intervals, but a difficulty to benefit from the passage of time to expect a visual stimulus. He presents additional difficulties in benefitting from temporal cues and adapting to changes in time delays. The impairments were ample enough to yield significant effects with analyses at the individual level. Although causal relationships between subjective and objective impairments cannot be established, the results show that exploring timing deficits at the individual level is possible in patients with schizophrenia. Besides, the results are consistent with hypotheses relating minimal self disorders (SDs) to timing difficulties. They suggest that both subjective and objective timing investigations should be developed further so that their use at an individual level can be generalized in clinical practice. (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)

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)

This article investigates “impaired insight,” a controversial psychiatric category describing a mad person unable to know his or her madness. Like “moral insanity” and other concepts before it, impaired insight offers a way to link the disparate logics of human responsibility in psychiatry and the law. I attribute its development to changes wrought by deinstitutionalization, the rise of antipsychotic medication, and patient incarceration in penal settings. In a system that aims to govern psychiatric patients through their freedom, the logic of (...) impaired insight introduces a wrinkle: can a person make an informed choice to refuse treatment if madness itself impairs awareness of illness? Drawing on tools from the sociology of science, I trace the process by which researchers recast psychodynamic “denial” as a neurological and therefore non-volitional “impairment” in the 1990s. I then show how social movement actors mobilized the materialized form in the legal and policy fields in the 2000s, bringing insight science to bear upon the very questions of custodial management and patient rights that gave birth to it. At stake is this dilemma: how can societies that simultaneously privilege individual responsibility and somatic accounts of behavior govern those at the border of legal capacity, and with what justification? (shrink)

Bodying Postqualitative Research posits the question of what happens when lived, fleshy human bodies engage in postqualitative research in education. It takes as its central concern research propositions aimed at dismantling the structures of humanism that typically govern research in education and uses postqualitative conceptions of data, methodology, and clarity in conjunction with insights from feminist science studies scholars to imagine how we might 'body' postqualitative work. This book uses the provocations offered by postqualitative research and takes these touchpoints to (...) dismantle dominant logics of research, born of neoliberalism and ongoing settler colonialism to offer alternative perspectives. Importantly, this book stays near to the body by proposing caffeine shakes, antipsychotic medications, and scars as moments to take seriously how bodies do researching practices. After each chapter, the book turns to poetry as a "fracture" or a moment of disruption to the rhythm of the text that incites readers to reconsider the previous chapter otherwise. It concludes by asking what bodying postqualitative research might mean for pedagogy and for propositions toward future inquiry. Drawing together the work of feminist science and education scholars oriented toward the biosciences and whose work has not yet been immersed into postqualitative scholarship in a sustained way, this book brings together a vein of feminist science studies theorizing that both deepens and troubles postqualitative scholarship through its focus on the politics of science and the possibilities of doing bodies with biology, culture, and life. The volume is suitable for students and scholars interested in postqualitative and embodied research methods in education, and feminist and gender studies. (shrink)

Previous work employing graph theory and nonlinear analysis has found increased spatial and temporal disorder, respectively, of functional brain connectivity in schizophrenia. We present a new method combining graph theory and nonlinear techniques that measures the temporal disorder of functional brain connections. Multichannel electroencephalographic data were windowed and functional networks were reconstructed using the minimum spanning trees of correlation matrices. Using a method based on Shannon entropy, we found elevated connection entropy in gamma activity of patients with schizophrenia; however, gamma (...) connection entropy remained elevated in patients with schizophrenia even after a reduction in symptoms due to treatment with antipsychotics. Our results are consistent with several possibilities: aberrant functional connectivity is epiphenomenal to schizophrenia, aberrant functional connectivity is a central feature but antipsychotics reduce symptoms by an independent mechanism, or connection entropy is not an appropriately sensitive measure of brain abnormalities in schizophrenia. (shrink)

The practice of covertly administering medication is controversial. Although condemned by some as overly paternalistic, others have suggested that it may be acceptable if patients have permanent mental incapacity and refuse needed treatment. Ethical, legal, and clinical considerations become more complex when the mental incapacity is temporary and when the medication actually serves to restore autonomy. We discuss these issues in the context of a young man with schizophrenia. His mother had been giving him antipsychotic medication covertly in his soup. (...) Should the doctor continue to provide a prescription, thus allowing this to continue? We discuss this case based on the “four principles” ethical framework, addressing the conflict between autonomy and beneficence/non-maleficence, the role of antipsychotics as an autonomy restoring agent, truth telling and the balance between individual versus family autonomy. (shrink)

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)

In lieu of an abstract, here is a brief excerpt of the content:Clinical CommentaryChong Siow Ann, Associate ProfessorDr. G appears to experiencing symptoms of schizophrenia, which is arguably the most severe mental disorder and which afflicts about one in a hundred people. This is a psychotic disorder that causes disturbances and distortions in thinking, including neurocognitive impairments, perception and behaviour. There is no cure for this often devastating disorder. Current antipsychotic medications can alleviate some of the symptoms but it often (...) comes at a price as these antipsychotics have burdensome side effects.A feature of this disorder is anosognosia, which is a lack of awareness or “insight” that an illness is present. This lack of insight presents a particular challenge because these individuals would, as in the case of Dr. G, refuse needed treatment as they do not perceive that they are ill. This is not necessarily an all-or-none phenomenon but is rather more complex and multidimensional; there might be an unawareness or recognition on behalf of the patient that they are suffering from a mental illness, the failure to appreciate the necessity of treatment; and/or the inability to recognise and define the psychotic symptoms like unusual thoughts and hallucinations as signs of illness1 and in many instances, all three are present. It is also by no means uncommon. Studies have found that between 60% and 80% of people with schizophrenia lack awareness of their illness to varying degrees.2This phenomenon remains an enigma. Some regard it as a form of psychological defence against the harsh reality of a psychotic illness — awareness of having a chronic and devastating illness might lead to demoralisation, hopelessness and suicide.3 Recent research, however, [End Page 250] indicates that this psychological denial plays a small part, if any, and instead has found an association with certain neuropsychological and neurocognitive deficits,4 as well as functional and structural brain abnormalities in the frontal lobe of the brain.5The prevailing clinical view thus is that this is an intrinsic and organic aspect of the schizophrenic illness which has nothing to do with wilfulness but rather the incapacity to perceive the presence of the illness. Edwin Fuller Torrey, an eminent psychiatrist and executive director of the Stanley Medical Research Foundation, calls anosognosia the “single largest reason why individuals with schizophrenia and bipolar disorder do not take their medications”, and he has remarked that “to keep talking about civil liberty is illogical. Patients are anything but free when they’re at the beck and call of their own delusions”.6It is also this view that it is a product of a brain disorder that some — particularly patients — find unacceptable. At one level, it does not take into context the person’s own experiences, and at a deeper level it calls into question the conception of the self with its capacity to exercise judgements and the autonomy to make decisions.This is a perennial ethical issue in psychiatry when people with severe mental illnesses refuse treatment. This becomes a Catch-22 situation where part of the illness that needs treatment is also preventing any treatment to be given: implicit in the principle of informed consent for treatment is that the person should be aware of the nature and course of their illness and acknowledge the need for treatment. While there are laws for involuntary commitment, the bar is usually high in that there must be a clear and present risk of harm to the person or others. Alan Stone, a professor of law and psychiatry at Harvard University proposed a possible justification for involuntary treatment based on his “thank-you theory” which assumes that patients will become well and subsequently agree that the intervention was in their best interests but research suggests that only half of these patients would admit so.7One suggested mechanism is the use of advance directives — psychiatry’s version of the living will in which people can specify what sort of medical care they would like should they become mentally unwell and unable to exercise appropriate judgement. An intrinsic part of this might include a “Ulysses contract” — just as Ulysess instructed his crew to lash him to the mast of the his ship so that he could... (shrink)

Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and (...) experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy. (shrink)

Current diagnostic criteria for schizophrenia place emphasis on delusions and hallucinations, whereas the classical descriptions of schizophrenia by Kraepelin and Bleuler emphasized disorganization and impoverishment of mental activity. Despite the availability of antipsychotic medication for treating delusions and hallucinations, many patients continue to experience persisting disability. Improving treatment requires a better understanding of the processes leading to persisting disability. We recently introduced the term classical schizophrenia to describe cases with disorganized and impoverished mental activity, cognitive impairment and predisposition to persisting (...) disability. Recent evidence reveals that a polygenic score indicating risk for schizophrenia predicts severity of the features of classical schizophrenia: disorganization, and to a lesser extent, impoverishment of mental activity and cognitive impairment. Current understanding of brain function attributes a cardinal role to predictive coding: the process of generating models of the world that are successively updated in light of confirmation or contradiction by subsequent sensory information. It has been proposed that abnormalities of these predictive processes account for delusions and hallucinations. Here we examine the evidence provided by electrophysiology and fMRI indicating that imprecise predictive coding is the core pathological process in classical schizophrenia, accounting for disorganization, psychomotor poverty and cognitive impairment. Functional imaging reveals aberrant brain activity at network hubs engaged during encoding of predictions. We discuss the possibility that frequent prediction errors might promote excess release of the neurotransmitter, dopamine, thereby accounting for the occurrence of episodes of florid psychotic symptoms including delusions and hallucinations in classical schizophrenia. While the predictive coding hypotheses partially accounts for the time-course of classical schizophrenia, the overall body of evidence indicates that environmental factors also contribute. We discuss the evidence that chronic inflammation is a mechanism that might link diverse genetic and environmental etiological factors, and contribute to the proposed imprecision of predictive coding. (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)

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)

Background: Treatment of psychotic disorders in pregnancy is often ethically and clinically challenging, especially when psychotic symptoms impair decision-making capacity. There are several competing ethical obligations to consider: the ethical obligation to maternal autonomy, the maternal and fetal beneficence-based obligations to treat peripartum psychosis, and the fetal beneficence-based obligation to minimize teratogenic exposure. Objective: This article outlines an ethical framework for clinical decision-making for the management of chronic psychosis in pregnancy, with an emphasis on special considerations in the previable and (...) periviable period. Case Presentation: A 31-year-old gravida 2, para 1 with intrauterine pregnancy at 12 weeks and 4 days gestation was brought to the emergency department by her husband seven months after delivering her first child, due to sudden onset of behavioral changes that included self-isolation, not eating, and not taking care of her child. Her past medical history included hypothyroidism and inflammatory bowel disease, but no prior psychiatric illness. After being admitted to the psychiatric hospital, she continued to have poor oral intake and weight loss despite initial inpatient treatment with antipsychotics, levothyroxine, and discontinuation of corticosteroids. Her pregnancy was also complicated by the diagnosis of multiple fetal anomalies at 20 weeks gestation, when the fetus was periviable. Conclusions: For previable or periviable pregnancies, the patient and/or surrogate should decide whether to pursue prenatal genetic screening and invasive diagnostic testing, as well as whether to continue or terminate the pregnancy. When the choice is made to continue the pregnancy, initiation of long-term psychiatric treatment (including medications with potential adverse fetal effects) should be based on shared decision-making between the physician and the patient and/or surrogate. Although some pharmacologic interventions may have potential adverse effects on the developing fetus, the use of psychotropic medications can be ethically justified, even if the patient herself does not have the capacity to consent and requires a surrogate, when the goal is to restore maternal autonomy and minimize the risks of maternal and fetal harm from untreated psychiatric illness. (shrink)

Background Obtaining informed consent in the clinical setting is an important yet challenging aspect of providing safe and collaborative care to patients. While the medical profession has defined best practices for obtaining informed consent, it is unclear whether these standards meet the expressed needs of patients, their families as well as healthcare providers. The authors sought to address this gap by comparing the responses of these three groups with a standardised informed consent paradigm. Methods Piloting a web-based ‘reverse’ simulation paradigm, (...) participants viewed a video showing a standardised doctor engaging in an informed consent discussion. The scenario depicted a simulated patient with psychotic symptoms who is prescribed an atypical antipsychotic medication. 107 participants accessed the simulation online and completed a web-based debriefing survey. Results Survey responses from patients, family members and healthcare providers indicated disparities in information retention, perception of the doctor's performance and priorities for required elements of the consent process. Conclusions To enhance existing informed consent best practices, steps should be taken to improve patient retention of critical information. Adverse events should be described in the short-term and long-term along with preventative measures, and alternative psychosocial and pharmacological treatment options should be reviewed. Information about treatment should include when the medication takes therapeutic effect and how to safely maintain the treatment. The reverse simulation design is a model that can discern gaps in clinical practice, which can be used to improve patient care. (shrink)

With more people in the world living into older age, Alzheimer's and other Dementias: The Facts takes a comprehensive look at the spread of dementia, and provides authoritative information and practical advice for sufferers, their families, and the medical professionals who care for them. -/- Written by a consultant in old age psychiatry, the book provides an overview of all the different types of dementia (including younger-onset dementias), from the most-recognized - Alzheimer's - to the less-frequent types, such as those (...) caused by inherited metabolic disorders or HIV. The book guides the reader step-by-step through how the brain works, and explains in clear and simple language the effect of dementias on the brain, and the impact on an individual's cognitive function. -/- A dedicated chapter explains how a diagnosis is reached, including the different modes of assessment, from blood tests carried out by a GP, to specialist scans, highlighting how the brain actually works. Detailed sections cover the latest treatments available, including the controversial use of antipsychotic medication, and the possibility of disease-modifying treatments in the future. -/- The book also explains how the multi-disciplinary team works together to look after the sufferer's social needs, such as bathing and washing, as well as their spiritual and palliative needs. Alzheimer's and other Dementias: The Facts provides all the relevant information and guidance for sufferers, family and their care-givers to choose the right intervention at the right time, to create - as the book advocates - a unique and personalized management plan. (shrink)

Electroacupuncture (EA) and electroconvulsive therapy (ECT) are often used in the management of schizophrenia. This study sought to determine whether additional EA and ECT could augment antipsychotic response and reduce related side effects. In this retrospective controlled study, 287 hospitalized schizophrenic patients who received antipsychotics (controls, n = 50) alone or combined with EA (n = 101), ECT (n = 55) or both (EA+ECT, n = 81) were identified. EA and ECT were conducted for 5 and 3 sessions per (...) week, respectively, with a maximum of 12 sessions for ECT during hospitalization. The Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were used to assess the severity of psychotic symptoms. Clinical response on SAPS and SANS, weight gain, and adverse events were compared. Survival analysis revealed that the ECT and EA+ECT groups had markedly greater clinical response rate than controls on SAPS [72.7% and 90.1% vs. 64.0%; relative risk (RR), 1.974 and 2.628, respectively, P ≤ 0.004] and on SANS (67.3% and 70.4% vs. 42.0%; RR, 1.951 and 2.009, respectively, P ≤ 0.015). A significantly greater response rate on SANS than controls was also observed in the EA group (64.4% versus 42.0%; RR = 1.938, P = 0.008). EA-containing regimens remarkably reduced weight gain and incidences of headache, insomnia, dry mouth, and electrocardiographic abnormalities. These results suggest that EA and ECT can serve as additional treatment for enhancing antipsychotic response and reduce the side effects in hospitalized patients with schizophrenia. (shrink)

Schizophrenia (SCZ) is a severe neurodevelopmental disorder affecting 1% of populations worldwide with a grave disability and socioeconomic burden. Current antipsychotic medications are effective treatments for positive symptoms, but poorly address negative symptoms and cognitive symptoms, warranting the development of better treatment options. Further understanding of SCZ pathogenesis is critical in these endeavors. Accumulating evidence has pointed to the role of mitochondria and metabolic dysregulation in SCZ pathogenesis. This review critically summarizes recent studies associating a compromised mitochondrial function with people (...) with SCZ, including postmortem studies, imaging studies, genetic studies, and induced pluripotent stem cell studies. This review also discusses animal models with mitochondrial dysfunction resulting in SCZ‐relevant neurobehavioral abnormalities, as well as restoration of mitochondrial function as potential therapeutic targets. Further understanding of mitochondrial dysfunction in SCZ may open the door to develop novel therapeutic strategies that can address the symptoms that cannot be adequately addressed by current antipsychotics alone. (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)

AimWhite matter changes in individuals at ultra-high risk for psychosis (UHR) may be involved in the transition to psychosis. Sleep-wake disturbances commonly precede the first psychotic episode and predict development of psychosis. We examined associations between white matter microstructure and sleep-wake disturbances in UHR individuals compared to healthy controls (HC), as well as explored the confounding effect of medication, substance use, and level of psychopathology.MethodsSixty-four UHR individuals and 35 HC underwent clinical interviews and diffusion weighted imaging. Group differences on global (...) and callosal mean fractional anisotropy (FA) was tested using general linear modeling. Sleep-wake disturbances were evaluated using the subjective measures disturbed sleep index (DSI) and disturbed awakening index (AWI) from the Karolinska Sleep Questionnaire, supported by objective sleep measures from one-night actigraphy. The primary analyses comprised partial correlation analyses between global FA/callosal FA and sleep-wake measures. Secondary analyses investigated multivariate patterns of covariance between measures of sleep-wake disturbances and FA in 48 white matter regions of interest using partial least square correlations.ResultsUltra-high risk for psychosis individuals displayed lower global FA (F = 14.56, p < 0.001) and lower callosal FA (F = 11.34, p = 0.001) compared to HC. Subjective sleep-wake disturbances were significantly higher among the UHR individuals (DSI: F = 27.59, p < 0.001, AWI: F = 36.42, p < 0.001). Lower callosal FA was correlated with increased wake after sleep onset (r = −0.34, p = 0.011) and increased sleep fragmentation index (r = −0.31, p = 0.019) in UHR individuals. Multivariate analyses identified a pattern of covariance in regional FA which were associated with DSI and AWI in UHR individuals (p = 0.028), but not in HC. Substance use, sleep medication and antipsychotic medication did not significantly confound these associations. The association with objective sleep-wake measures was sustained when controlling for level of depressive and UHR symptoms, but symptom level confounded the covariation between FA and subjective sleep-wake measures in the multivariate analyses.ConclusionCompromised callosal microstructure in UHR individuals was related to objectively observed disruptions in sleep-wake functioning. Lower FA in ventrally located regions was associated with subjectively measured sleep-wake disturbances and was partly explained by psychopathology. These findings call for further investigation of sleep disturbances as a potential treatment target. (shrink)

The analysis presented in this article reveals an ambiguity and tension in human rights theory concerning the delusional person’s freedom of belief and thought. Firstly, it would appear that the concepts ‘opinion’ and ‘thought’ are defined in human rights discussion in such a way that they do include delusions. Secondly, the internal freedom to hold opinions and thoughts is defined in human rights discussion and international human rights covenants as an absolute human right which should not be restricted in any (...) situation for any reason. These views, if understood literally, imply that a person has an absolute right to hold a delusion. However, this kind of conclusion has not been made in mental health laws, the ethical principles guiding psychiatric care or the practice of psychiatry. Instead, they assume that the use of involuntary antipsychotic medication is justified even thought its purpose is to influence delusions. The ambiguity and tension in human rights theory concerning the freedom of belief and thought challenge us to develop this theory within an interdisciplinary discussion so that people with delusions are taken into account properly. (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)

This manuscript describes the responses and correlates of outpatients with schizophrenia spectrum disorders to a tool designed to measure comprehension before obtaining informed consent for research participation. We used the Evaluation to Sign Consent form to document comprehension in 100 outpatients as part of their consent to participate in an ongoing study of an exercise intervention. The findings suggest that using this form is a feasible and acceptable approach to documenting comprehension of research procedures prior to obtaining informed consent. Age (...) 49 years and older and the receipt of intramuscular antipsychotic medication predicted the need for additional assistance to complete the Evaluation to Sign Consent form successfully (χ2 = 8.29, P = 0.016). Nurse researchers should consider documenting comprehension with this tool owing to its availability, time efficiency and utility. (shrink)