The future of depression psychopharmacology

Along with the development of selective serotonin reuptake inhibitors there has been a tremendous widening of the definition of depression and an impressive decrease in the placebo-drug difference in controlled studies. In the early 1960s, about one third of depressed patients improved with placebo and two thirds with active compounds. Current controlled studies suggest that the situation has certainly not improved. The Sequenced Treatment Alternatives to Relieve Depression Study found that response rates to new compounds after the failure of the first antidepressant are low. The monoamine hypothesis of depression was formulated in the mid 1960s based on the antidepressant efficacy of the monoamine reuptake inhibitors, monoamine oxidase inhibitors, and the depressogenic effects of reserpine as a monoamine depleter. However, no monoamine-related finding has been found that is diagnostic for depression. A second major hypothesis regarding depression has been the stress cortisol hypothesis. However, blood cortisol levels are not diagnostic of depression. Psychiatric clinicians are convinced that there are patients for whom antidepressants have made the difference between life and death. However, physicians may generalize unjustifiably based on single dramatic cases to a much larger diagnostic group. Perhaps there are many causes of different types of human sadness, and perhaps only some of these involve mechanisms related to monoamines. Thus, perhaps only some kinds of depression are responsive to monoamine affecting antidepressants..     

Neuroscience and psychopharmacology into the next millennium

The end of the millennium provides an opportunity to review some of the common practices that were present in psychopharmacology during the 20th century. The author focuses on two approaches that have dominated research and guided the clinical application of psychopharmacologic therapeutics: the unitary clinically-based and single-lesion perspectives. The author expands upon these older formulations of neuropsychiatric disease pathogenesis and describes how the approach to psychopharmacologic research and therapeutics has changed in light of advances in the basic neurosciences. Relevant recent advances in the basic neurosciences that shed light on the pathophysiology of neuropsychiatric disease states and that guide psychopharmacologic practices are described. The use of atypical antipsychotic agents to treat schizophrenia is given as one example of the clinical applications of the approach to psychopharmacology in the next century.     

Computational psychiatry

Computational ideas pervade many areas of science and have an integrative explanatory role in neuroscience and cognitive science. However, computational depictions of cognitive function have had surprisingly little impact on the way we assess mental illness because diseases of the mind have not been systematically conceptualized in computational terms. Here, we outline goals and nascent efforts in the new field of computational psychiatry, which seeks to characterize mental dysfunction in terms of aberrant computations over multiple scales. We highlight early efforts in this area that employ reinforcement learning and game theoretic frameworks to elucidate decision-making in health and disease. Looking forwards, we emphasize a need for theory development and large-scale computational phenotyping in human subjects.     

The use of psychopharmacology to study reciprocal influences in parent-child interaction

The present paper reviews the possible utility and limitations of using behavior-modifying drugs to study reciprocal influences in parent-child interactions. Ideal circumstances for use of this approach are outlined and contrasted with the current status of the field of psychopharmacology. Numerous limitations to the approach are found. Yet the utility of the design is demonstrated in several studies of stimulant drug effects on the mother-child interactions of hyperactive children, and in one pilot study of the effects of diazepam, an anxiolytic, on these same interactions. The major pitfalls to this approach will quite likely be overcome by future research and the development of safer, more highly specific behavior-modifying drugs.Funding for this paper is derived from Grant No. 1-R01-MH32334-01 from the National Institute of Mental Health.     

The ethics of clinical innovation in psychopharmacology: Challenging traditional bioethics

Objective  

To assess the scientific and ethical basis for clinical innovation in psychopharmacology.     

The ethics of clinical innovation in psychopharmacology: Challenging traditional bioethics

Advance health care directives and informed consent remain the cornerstones of patients' right to self-determination regarding medical care and preferences at the end-of-life. However, the effectiveness and clinical applicability of advance health care directives to decision-making on the use of life support systems at the end-of-life is questionable. The Uniform Anatomical Gift Act (UAGA) has been revised in 2006 to permit the use of life support systems at or near death for the purpose of maximizing procurement opportunities of organs medically suitable for transplantation. Some states have enacted the Revised UAGA (2006) and a few of those have included amendments while attempting to preserve the uniformity of the revised Act. Other states have introduced the Revised UAGA (2006) for legislation and remaining states are likely to follow soon. The Revised UAGA (2006) poses challenges to the Patient Self Determination Act (PSDA) embodied in advance health care directives and individual expression about the use of life support systems at the end-of-life. The challenges are predicated on the UAGA revising the default choice to presumption of donation intent and the use of life support systems to ensure medical suitability of organs for transplantation. The default choice trumps the expressed intent in an individual's advance health care directive to withhold and/or withdraw life support systems at the end-of-life. The Revised UAGA (2006) overrides advance directives on utilitarian grounds, which is a serious ethical challenge to society. The subtle progression of the Revised UAGA (2006) towards the presumption about how to dispose of one's organs at death can pave the way for an affirmative "duty to donate". There are at least two steps required to resolve these challenges. First, physicians and hospitals must fulfill their responsibilities to educate patients on the new legislations and document their preferences about the use of life support systems for organ donation at the end-of-life. Second, a broad based societal discussion must be initiated to decide if the Revised UAGA (2006) infringes on the PSDA and the individual's right of autonomy. The discussion should also address other ethical concerns raised by the Revised UAGA (2006), including the moral stance on 1) the interpretation of the refusal of life support systems as not applicable to organ donation and 2) the disregarding of the diversity of cultural beliefs about end-of-life in a pluralistic society.     

Prophylactic psychiatry

The great contributions of Gantt to the problems of prophylactic psychiatry are pointed out. The author reviews his experiences with a 30-year follow-up of a population of 1800 persons. Over the 30 years, there appeared to be a 50% increase of neuroses, which raises great problems for mental health services. The Berlevåg population was offered optimal psychiatric services. Behavior therapy of neuroses and drug treatment of depression may possibly have lowered the prevalence of mental disorders. Psychophysiologic tests were used in the project. It is hoped that such tests may be utilized for early detection and treatment of mental disorders.     

Principles of computer-assisted classification in psychiatry

The use of computer based diagnostic decision and artificial intelligence are discussed in relation to the problems of validity and reliability of psychiatric diagnoses. The authors suggest a definition of a computer aided classificator as an existent decision system for an automatically analysis of findings.     

New trends in philosophy of psychiatry

The concept of mental disorder is often defined by reference to the notion of mental dysfunction, which is in line with how the concept of disease in somatic medicine is often defined. However, the notions of mental function and dysfunction seem to suffer from some problems that do not affect models of physiological function. Functions in general have a teleological structure; they are effects of traits that are supposed to have a particular purpose, such that, for example, the heart serves the goal of pumping blood. But can we single out mental functions in the same way? Can we identify mental functions scientifically, for instance, by applying evolutionary theory? Or are models of mental functions necessarily value-laden? I want to identify several philosophical problems regarding the notion of mental function and dysfunction and point out some possible solutions. As long as these questions remain unanswered, definitions of mental disorder that rest upon the concept of mental dysfunction will lack a secure foundation.     

Brief therapy in adult psychiatry

Forty-one of forty-four referrals to a multidisciplinary team providing brief therapy in adult psychiatry were followed up after one year. Questionnaires were sent to attenders and their general practitioners. A good outcome was reported in 29 cases (70%) while four cases (10%) were worse. Good outcome was linked with more therapy sessions and having specific goals for treatment. Lower social class did not predict poor outcome, unlike other forms of psychotherapy. Benefit was not linked to age, sex, place of residence, duration of problem, source of referral, those attending, inpatient status or lapse from treatment. Longstanding problems did slightly less well. The 'worse' group were younger and all four were female. Training of the team took place during therapy at little extra cost without any detriment to outcome. These findings have implications for the team's approach and for the provision of psychotherapy services in general.