The Dobson-Rawlins pact and the National Institute for Health and Care Excellence: impact of political independence on scientific and legal accountability.

This analysis considers whether the independence of the National Institute for Health and Care Excellence (NICE), while safeguarding guidelines from commercial lobbying, may render NICE legally and scientifically unaccountable. The analysis examines the role of judicial reviews and stakeholder consultations in place of peer review in light of current debates concerning the depression guideline.

Restricción química en ancianos institucionalizados, el proyecto chrome / No disponible

En los últimos años se ha ido cuestionando con cada vez mayor asiduidad la práctica psiquiátrica habitual en los pacientes ancianos con o sin demencia, institucionalizados o no institucionalizados. El motivo de ese cuestionamiento es el empleo frecuente de medidas de restricción física y de psicofármacos en estos pacientes, práctica que con frecuencia constituye lo que se denomina sujeción física o química. Este artículo se focaliza en la medida de sujeción más desconocida, que es la sujeción química, debido al empleo inadecuado de psicofármacos. Se repasarán causas, dinámicas y soluciones propuestas con respecto al empleo de sujeciones, así como los usos de psicofármacos que pueden ser considerados sujeción química. Además, se resumirán aspectos importantes del proyecto CHROME, pionero en España en sistematizar el abordaje de las sujeciones químicas

The usual psychogeriatric clinical practice regarding elderly patients with or without dementia living at home or in an institution has been questioned in recent years. The reason is the frequent use of physical and chemical restraints in this population. This article focusses on chemical restraints, the most unknown measure of them, when an inappropriate use of psychoactive drugs occurs. We review reasons, dynamics and solutions for restraints `s use and when the use of a drug can be considered a chemical restraint. In addition, we summarize the most important aspects of the CHROME criteria, the first initiative in Spain to systematize the chemical restraints use

Neuroethics: the pursuit of transforming medical ethics in scientific ethics.

Ethical problems resulting from brain research have given rise to a new discipline termed neuroethics, representing a new kind of knowledge capable of discovering the neural basis for universal ethics. The article (1) tries to evaluate the contributions of neuroethics to medical ethics and its suitability to outline the foundations of universal ethics, (2) critically analyses the process of founding this universal ethic. The potential benefits of applying neuroimaging, psychopharmacology and neurotechnology have to be carefully weighed against their potential harm. In view of these questions, an intensive dialogue between neuroscience and the humanities is more necessary than ever.

Neuroethics: the pursuit of transforming medical ethics in scientific ethics

Ethical problems resulting from brain research have given rise to a new discipline termed neuroethics, representing a new kind of knowledge capable of discovering the neural basis for universal ethics. The article (1) tries to evaluate the contributions of neuroethics to medical ethics and its suitability to outline the foundations of universal ethics, (2) critically analyses the process of founding this universal ethic. The potential benefits of applying neuroimaging, psy-chopharmacology and neurotechnology have to be carefully weighed against their potential harm. In view of these questions, an intensive dialogue between neuroscience and the humanities is more necessary than ever.

Present and future of developmental neuropsychopharmacology.

The field of child and adolescent psychiatry has always lagged behind adult psychiatry. With recent evidence that the vast majority of mental disorders, even when they emerge in adulthood, cause abnormal neurodevelopment and resultant emphasis on prevention and early intervention, there is a need to put child psychiatry at the top of the agenda in mental health research. This should also be the case for developmental neuropsychopharmacology. The target of drug discovery should shift toward a population younger than the one that is typically included in clinical trials. This is not only a matter of trying to replicate what has been found in individuals with mature brains; it is about searching for new strategies that address developing brains while the therapeutic window for their effect is still open. At present, major concerns in developmental psychopharmacology are over-prescription rates and use of psychotropic medications for conditions with a particularly underdeveloped evidence base, as well as adverse effects, especially potentially life-shortening cardiometabolic effects and suicidal ideation. The future of research in this area should focus on the use of drugs for primary and secondary prevention that would modify abnormal brain development.

El uso adecuado de medicamentos en pacientes con enfermedad de Alzheimer / Proper use of drugs in patients with Alzheimer's disease

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Reflections on ethical issues in psychopharmacology: an American perspective.

Psychopharmacology has revolutionized psychiatric practice but raises a number of ethical issues. This review from an American perspective first describes ethics analyses and attempts to portray the ethical practitioner. Pressures that interfere with appropriate prescribing come from outside the prescriber and from within, including from insurers, other treatment staff and the prescriber's own will to act for the patient. Clinicians also face binds in which alternate choices seem to have merit and leave the prescriber feeling pulled in contradictory directions, frequently related to risk-benefit dilemmas. The ethics of psychopharmacology poses many questions that cannot yet be answered at the current state of the field. Pharmacology also seems to promote extremes of attitudes, such as "All such drugs are poisons" and the like. This review then provides some risk management principles, and concludes that such a review, though not comprehensive, may serve to open questions that are not always considered by clinicians.

The placebo arm in clinical studies for treatment of psychiatric disorders: a regulatory dilemma.

BACKGROUND: The use of placebo in clinical trials, and, related to this, ethical and feasibility aspects, are often debated. However, regulatory authorities must ensure that only new drugs with a positive benefit/risk would be granted a marketing authorization. It is therefore not surprising that they often put forward the need for placebo control in clinical trials in an area where many trials fail, and assay sensitivity is not self-evident. To illustrate the complexity that regulatory authorities encounter when faced with the registration dossier of products in the main psychiatric therapeutic areas, Major Depressive Disorder (MDD) and schizophrenia, the trial outcome for products receiving an opinion in the EU during the past 15 years were reviewed. DATA SOURCE: European Public Assessment Reports and registration files. RESULTS: A total of 45 studies qualified for analysis. For the indication MDD 38% of the studies (10/26) were recorded as failed, and another 15% (4/26) as negative. For schizophrenia, these figures were 16% (3/19) and 11% (2/19). Further exploration of the trials in MDD revealed an inconsistent pattern in terms of magnitude of placebo- and drug-mediated response (i.e. similar studies with consistent placebo response provided different treatment outcomes). CONCLUSION: From a regulatory perspective the dilemma of a priori exclusion of the placebo arm in clinical trials in the domains of depression or schizophrenia cannot be solved at this time as long as factors influencing trial variability are not better identified or understood. This counts in particular for MDD where the added drug effect is not consistent across trials with almost identical inclusion criteria. Unfortunately, this trend has not changed over the past 15 years. However, all efforts should be taken to optimize the clinical development of drugs in the psychiatric domain, and improve the intrinsic quality of the clinical trials in order to allow for a different viewpoint.

Psychiatry should not become hostage to placebo: an alternative interpretation of antidepressant-placebo differences in the treatment response in depression.

BACKGROUND: It is widely believed that in randomized controlled trials of antidepressants the difference between drug and placebo response rates is rather small (around 20%), leading to a common perception that antidepressants have limited efficacy. AIM: The aim of the present paper was to present an alternative calculation and interpretation of antidepressant-placebo difference in the treatment response to antidepressant in drug trials which may shed a new light on the efficacy of antidepressants. ISSUES: We have previously highlighted several controversial points concerning the calculation of antidepressant and placebo response rates in randomised controlled trials, which may influence views concerning the efficacy of drugs, and demonstrated several factors which may lead to overestimation of the placebo effect and underestimation of antidepressant efficacy. The traditional interpretation of antidepressant-placebo difference in randomized controlled trials on major depression has been also challenged previously from at least five points of view but all leading to a conclusion that currently prevailing opinions concerning relative placebo and antidepressant response rates overestimate placebo response, and thereby underestimate efficacy of antidepressant drugs. In our present paper we propose another method for calculating placebo and antidepressant response rates which may shed new light on an overlooked aspect of the efficacy of these drugs. CONCLUSIONS: We contend that opinions on the effectiveness of antidepressants should be reconsidered, and comparisons with placebo should be more carefully applied. Interpretation of the placebo response is of crucial importance for establishing the efficacy of antidepressive medications, and psychiatry should not become the hostage of placebo.

Those famous red pills-Deliberations and hesitations. Ethics of placebo use in therapeutic and research settings.

Placebo fascinates and mystifies. Even with today's medical science we still do not know how and if it works. The use of placebo both in therapy and in research evokes ethical problems that are not easily resolved either. Placebo is intrinsically linked to deception, while veracity is a basic tenet in today's thinking of a doctor-patient relationship. In research ethics placebo, though considered the golden control condition, leads to the question of the therapeutic obligation. This narrative review presents an overview of these ethical questions and offers considerations that are of relevance to daily medical and research practice both in psychiatry and elsewhere.

El papel de la serendipia en el descubrimiento de los efectos clínicos de los psicofármacos: más allá del mito / The role of serendipity in the discovery of the clinical effects of psychotropic drugs: beyond of the myth

La serendipia es la facultad de realizar un descubrimiento mediante una combinación de accidente y sagacidad. En el ámbito de la psicofarmacología, la serendipia jugó un papel fundamental en el descubrimiento de muchos agentes psicotrópicos, aunque existen marcadas controversias en este particular, posiblemente debido a divergencias semánticas en relación al significado de este término. Nosotros hemos aplicado una definición operativa de serendipia basada en el hallazgo de algo no esperado o no buscado intencionalmente, independientemente del proceso sistemático que condujo a la observación accidental. En el presente trabajo, se analizan algunos ejemplos representativos de descubrimientos en el campo de la psicofarmacología según diferentes patrones de intervención serendípica. De acuerdo con este criterio existirían cuatro patrones diferentes de imputabilidad serendípica: descubrimientos serendípicos puros(ácido valproico/valproato); descubrimientos serendípicos iniciales que conducen a descubrimientos no serendípicos (imipramina); descubrimientos no serendípicos asociados secundariamente a descubrimientos de caracter serendípico(barbitúricos); descubrimientos no serendípicos (haloperidol). Podemos concluir que los descubrimientos serendípicos puros en este campo no son muy frecuentes, siendo más habitual un patrón mixto, que parte de una observación inicial serendípica que conduce a un descubrimiento no serendípico de utilidad clínica. Este es el caso de la imipramina, las sales de litio, la clorpromazina o el meprobamato (AU)

The serendipity is the faculty for making a discovery through a combination of accident and sagacity. In psychopharmacology, the serendipity played a key role in the discovery of many psychotropic drugs, although there are marked disputes in this regard, possibly due to semantic differences in relation to the meaning of this term. We have implemented an operational definition of serendipity based on the discovery of something un expected or not sought intentionally, irrespective of the systematic process leading to the accidental observation. The present paper analyses some representative examples of discoveries in the field of psychopharmacology according to different serendipitous intervention patterns. Following this approach there would be four different imputability patterns: pure serendipitous discoveries (valproic acid/valproate); serendipitous observation leading to a non-serendipitous discoveries (imipramine); non-serendipitous discoveries secondarily associated with serendipitous observation (barbiturates); non-serendipitous discoveries (haloperidol). We can conclude that pure serendipitous discoveries in this field are not very frequent, most common being a mixed pattern; an initial serendipitous observation which leads to a non-serendipitous discovery of clinical utility. This is the case of imipramine, lithium salts, chlorpromazine or meprobamate (AU)

Head to head comparisons as an alternative to placebo-controlled trials.

Head to head trials have been proposed as an alternative to the ethical and methodological concerns related to placebo-controlled trials. While those studies may be particularly informative from the clinical and cost-effectiveness point-of-view, avoiding placebo poses several regulatory concerns: for superiority designs, the choice of the trial population, outcomes, dose and escalation of the comparator, as well as the comparator itself may be an issue; for non-inferiority studies, issues related to uncertain assay sensitivity and exposure of large samples to potentially ineffective or unsafe drugs make them inappropriate, in the absence of a previous positive superiority trial, for regulatory purposes. The inclusion of active comparators in regulatory trials should not be seen as an alternative, but as a useful complement to the information that can be obtained from placebo-controlled studies.

The ethics of elective psychopharmacology.

Pharmacological cognitive enhancers (PCEs) are used to improve cognitive functions, such as attention, learning, memory and planning in patients with impairments in cognition resulting from traumatic brain injury (TBI) or from neuropsychiatric disorders such as Alzheimer's disease (AD), mild cognitive impairment, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Moreover, PCEs have been shown to improve cognition in healthy volunteers with no psychiatric disorders. This article describes the rationale behind the need for their use in neuropsychiatric patients and illustrates how PCEs can ameliorate cognitive impairments, improve quality of life and wellbeing, and therefore reduce the economic burden associated with these disorders. We also describe evidence that PCEs are being used as cognitive enhancers by healthy people. Crucially, as the lifestyle use of these drugs becomes very popular in the healthy population, a final aim is to present an overview of the current and future neuroethical considerations of enhancing the healthy brain. As information regarding their actual use, benefits and harms in various healthy populations is currently lacking, we propose research that aims to obtain relevant empirical data, monitor the short- and long-term effectiveness and side-effects, and initiate accurate surveys to determine current patterns and quantity of usage of PCE drugs by healthy people. Furthermore, in order to instigate a dialogue between neuroethics and neuropsychopharmacology, we urge scientists to explore and communicate the social and ethical implications of their research to the public. Finally, we discuss and highlight other means of enhancing cognition in both patients and healthy adults, including education and physical exercise.

Treatment of sex offenders in Israeli prison settings.

The number of incarcerated sex offenders in the Israeli prison system has steadily increased during the past decade. While treatment of sex offenders is complex, treatment of those in prison seems to be more challenging. This publication presents major considerations and dilemmas, clinical as well as ethics-related, derived from the experience of the psychiatric division in the Israeli prison service in treating sex offenders in this special setting. The psychiatrist treating the incarcerated offender must always maintain a sensitive balance between the needs and wishes of his patient and the potential threat to society stemming from recidivism.

Ethical considerations in clinical training, care and research in psychopharmacology.

Psychopharmacology is a powerful tool in psychiatry; however, it is one that demands responsibility in order to deal with the ethical complexities that accompany advances in the field. It is important that questions are asked and that ethical mindfulness and sensitivity are developed along with clinical skills. In order to cultivate and deepen ethical awareness and subsequently solve issues in optimal fashion, investment should be made in the development of an ethical decision-making process as well as in education in the ethics of psychopharmacology to trainees in the field at all stages of their educational development. A clear approach to identifying ethical problems, engaging various ethical concepts in considering solutions and then applying these principles in problem resolution is demanded. An openness in identifying and exploring issues has become crucial to the future development and maturation of psychopharmacologists, both research and clinical. Consideration must be given to the social implications of psychopharmacological practice, with the best interests of patients always paramount. From both a research and clinical perspective, psychopharmacology has to be practised with fairness, sensitivity and ethical relevance to all. While ethical issues related to psychopharmacological practice are varied and plentiful, this review focuses on advances in technology and biological sciences, personal integrity, special populations, and education and training.

Safeguarding children's rights in psychopharmacological research: ethical and legal issues.

OBJECTIVE: Research on psychopharmacological treatment in children and adolescents is the subject of ongoing ethical discussion, as minors with mental disorders constitute a vulnerable patient group. Considering the important legislative changes in pediatric research over the past decade in both the US and Western Europe, there is a need to review recent developments in this area. METHOD: Based on a systematic literature review, a hermeneutical analysis focusing the main issues of ethics in child and adolescent psychopharmacology is provided. Legal and regulatory aspects of psychopharmacological research in children are compared between the US and Europe. Relevant issues were informed assent and consent to research participation, minimal risk and burden of research, ethics of pharmacogenetics, research on "me-too" medications, and justice in global research. Additionally, the concern about undue influence of financial interests in research is also addressed. CONCLUSION: Incentives for the conduct of clinical trials with children comparable to those contained in US legislation are now provided in the EU. Research to develop "me-too" preparations may have no significant benefit for children, but can cause research burden and detract from clinically more important projects by utilizing limited investigator time and patient resources. Thus far, pharmacogenetic studies may bring more individualized treatment approaches into child psychiatry but they remain at present a promise for the future. Finally, the issues of avoiding undue influence from funders and conflicts of interest remain a prominent concern which can be solved by declaring conflicts and publishing all results of studies extensively.

Psicofarmacología e infancia. ¿Dónde reside la ética? / Psychopharmacology and childhood: Where ethics are?

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