The cost and impact of compulsivity: A research perspective.

Compulsivity is the defining feature of various psychiatric disorders including Obsessive Compulsive Related Disorders (OCRDs), and other compulsive, impulsive, and addictive disorders. These disorders are disabling, chronic conditions with an early onset and high rates of comorbidity, misdiagnoses, and delay in treatment onset. Disorders of compulsivity are responsible for considerable socioeconomic burden to society. We review the costs and impacts of compulsivity. In order to facilitate earlier diagnosis and targeted treatments, we examine the overlapping mechanisms that underlie compulsivity. We reconceptualize psychiatric disorders based on core features of compulsivity, highlight challenges in harmonizing research in children and adults, describe newer research methodologies, and point to future directions that can impact the costs and impact of disorders of compulsivity.

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.

Neuroscience, power and culture: an introduction.

In line with their vast expansion over the last few decades, the brain sciences -- including neurobiology, psychopharmacology, biological psychiatry, and brain imaging -- are becoming increasingly prominent in a variety of cultural formations, from self-help guides and the arts to advertising and public health programmes. This article, which introduces the special issue of "History of the Human Science" on "Neuroscience, Power and Culture," considers the ways that social and historical research can, through empirical investigations grounded in the observation of what is actually happening and has already happened in the sciences of mind and brain, complement speculative discussions of the possible social implications of neuroscience that now appear regularly in the media and in philosophical bioethics. It suggests that the neurosciences are best understood in terms of their lineage within the "psy"-disciplines, and that, accordingly, our analyses of them will be strengthened by drawing on existing literatures on the history and politics of psychology -- particularly those that analyze formations of knowledge, power and subjectivity associated with the discipline and its practical applications. Additionally, it argues against taking today's neuroscientific facts and brain-targetting technologies as starting points for analysis, and for greater recognition of the ways that these are shaped by historical, cultural and political-economic forces.

The problem of the psychopharmacologist.

OBJECTIVE: The psychopharmacologist designation currently pervades and heavily influences the practice, perception, and teaching of clinical psychiatry. The authors hope to make a case and provide the raw material for informed discussion of this role during psychiatric residency training. METHOD: A definition for the psychopharmacologist is sought. Historical trends in psychiatry which contributed most to its evolution are explored. Problems of the psychopharmacologist role are delineated. Extant solutions to psychiatry's problematic adaptation to an increasingly biological clinical role are critiqued, and a more effective one is pursued. RESULTS: The term psychopharmacologist seems linked to presumed scientific and medical approaches, a goal of symptom relief through medication, and often other providers who are considered patients' "primary" treaters. The role derives largely from economic and remedicalization trends. Aspects of disengagement are determined to form the core problem of the psychopharmacologist. The authors propose that psychiatry is defined by its practice of the medical model and call attention to three areas where the psychopharmacologist role and the medical model collide. CONCLUSIONS: Engaging psychiatric residents in a new dialogue about their role as physician will challenge the previously unquestioned psychopharmacologist categorization, begin to address its problems, and bring a vital element to trainees' professional identity development.

An update on publicly funded multisite trials in pediatric psychopharmacology.

In the last 10 years, the National Institute of Mental Health has funded a number of multisite clinical trials in pediatric psychopharmacology. Trials have been completed or are in progress in attention-deficit hyperactivity disorder, depression, autism, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and other anxiety disorders. Direct comparison between different treatment modalities, such as pharmacotherapy and psychotherapy, alone or in combination, has been the focus of a number of these studies, to inform clinicians and families of the relative therapeutic benefits of alternative interventions. This article presents a brief overview of these studies.

The growth of psychopharmacology in the 1990s: evidence-based practice or irrational exuberance.

The rapid growth in sales of psychotropic medications during the late 1980s and 1990s, eventually reaching $20 billion/year, reflected the increased use of seritonin reuptake inhibitors for depression and atypical antipsychotics for schizophrenia. Recently, however, some of the therapeutic claims for these medications have been challenged, and under-appreciated risks have turned out to be significant liabilities. Drug manufacturers increasingly dominate clinical trials research and evidence suggests that study designs and data presentations have been slanted to show products in a favorable light while unfavorable data were suppressed. At the same time, during the 1990s, potentially independent voices did not effectively or consistently present countervailing views. The extensive financial ties between the pharmaceutical industry and academic researchers, professional associations, and consumer groups may also have discouraged expression of critical views. Additionally, the narrow legal mandate of the FDA to evaluate the safety and efficacy of new drugs only in comparison to placebo (rather than in comparison to other treatments) probably limited its contribution. In the absence of reliable, impartial research on the risk and benefits of psychotropic medications, both before and after they are brought to market, pharmacy benefits management cannot achieve its goal of maximizing health care benefits per dollar spent. Further institutional support is needed for independent research, either conducted or funded by the federal government.

The emerging role of pharmacogenetics: implications for clinical psychiatry.

OBJECTIVE: This article aims to review the implications of pharmacogenetics for clinical psychiatry; these are discussed in the context of environmental and sociocultural factors. METHOD: A selective literature review was conducted using Medline search and other relevant references available to the authors. RESULTS: The individual differences in therapeutic and adverse effects of psychotropic drugs are largely determined by genetic factors. Recent advances in pharmacogenetics have highlighted the potential utility in predicting metabolic phenotypes, risks for side-effects and likelihood of drug response for the individual patient. CONCLUSIONS: Genotyping, especially for drug metabolizing enzymes, could enable more rational, cost-effective and optimal prescribing in future psychopharmacotherapy. Although the advances of pharmacogenetics may have many benefits in clinical practice, the importance of non-genetic factors must also be considered as cultural and environmental factors significantly impinge on response to medications. To clarify the extent pharmacogenetics can be adopted in clinical practice to predict drug response in patients from diverse backgrounds, further studies in different ethnic groups and clinical settings are required.

The interface between publicly funded and industry-funded research in pediatric psychopharmacology: opportunities for integration and collaboration.

Pediatric psychopharmacology research is undergoing a major expansion consequent to increasing use of psychotropic medications in children and recent legislative incentives to industry. In this rapidly changing context, the interface between publicly and privately funded research needs to be reconsidered to integrate activities and avoid unnecessary duplication of efforts. Once, by default, the almost exclusive domain of public research, child research is now increasingly funded by industry. There are, however, important issues unlikely to be addressed through private funding for which public support is needed, such as direct comparisons between active medications, between pharmacological and psychosocial interventions, or between combined and single treatment modalities; development of effective treatment strategies for patients unresponsive to first-line treatments; development of better research methods to assess efficacy and safety; identification of moderators and mechanisms of treatment response; and impact of treatment on illness course and prognosis. Industry-sponsored research is limited by the restricted access to proprietary databases, which impedes independent analyses and meta-analyses. Translation of basic neuroscience discoveries into treatment applications for children with mental illness is a critical area of inquiry that can benefit from integration of efforts and collaborations among academia, government, and industry.