Choice between food and heroin: effects of morphine, naloxone, and secobarbital.

Baboons responded on a choice task on which discrete trials involved choosing between an intravenous injection of heroin (.32 or 1.0 mg/kg) or the availability of food pellets. An intertrial interval of three hours followed the completion of each trial. Under baseline conditions baboons consistently completed the eight available trials each day. Typically, animals chose heroin on three or four trials a day and food on the remaining trials. Animals tended to space the selection of heroin rather than choosing heroin on consecutive trials. A series of single-day experimental manipulations was undertaken to characterize performance further. Manipulation of the heroin dose produced shifts in the relative frequency of choosing the drug option which were inversely related to dose. Manipulation of number of pellets per food trial produced little change in distribution of choices. Noncontingent administration of morphine produced dose-related decreases in relative frequency of heroin choices, and a higher dose decreased the number of trials completed. Noncontingent naloxone produced dose-related increases in the relative frequency of heroin choices. Noncontingent secobarbital had no effect on distribution of choices, and high doses reduced the number of trials completed per day. The results suggest that morphine and naloxone produce shifts in this choice behavior by selectively interacting with the reinforcing properties of the option involving heroin.     

Using empirical data to inform the ethical evaluation of placebo controlled trials

There has been considerable debate about the ethical acceptability of using placebo-controls in clinical research. Although this debate has been rich in rhetoric, considering that much of this research is predicated upon the assumption that data from this research is vital to clinical decision-making, it is ironic that researchers have introduced little data into these discussions. Using some published research concerning the use of placebo-controls in clinical research in hypertension and psychiatric drug trials, I suggest some ways that such data might be incorporated into the ethical analysis concerning placebo use in clinical trials. This approach promises to be important for enhancing conceptual and scientific understanding as well as public policy decision-making. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

What makes placebo-controlled trials unethical?

The leading ethical position on placebo-controlled clinical trials is that whenever proven effective treatment exists for a given condition, it is unethical to test a new treatment for that condition against placebo. Invoking the principle of clinical equipoise, opponents of placebo-controlled trials in the face of proven effective treatment argue that they (1) violate the therapeutic obligation of physicians to offer optimal medical care and (2) lack both scientific and clinical merit. We contend that both of these arguments are mistaken. Clinical equipoise provides erroneous ethical guidance in the case of placebo-controlled trials, because it ignores the ethically relevant distinction between clinical trials and treatment in the context of clinical medicine and the methodological limitations of active-controlled trials. Placebo controls are ethically justifiable when they are supported by sound methodological considerations and their use does not expose research participants to excessive risks of harm.     

Risk and Trust in Public Health: A Cautionary Tale

The leading ethical position on placebo-controlled clinical trials is that whenever proven effective treatment exists for a given condition, it is unethical to test a new treatment for that condition against placebo. Invoking the principle of clinical equipoise, opponents of placebo-controlled trials in the face of proven effective treatment argue that they (1) violate the therapeutic obligation of physicians to offer optimal medical care and (2) lack both scientific and clinical merit. We contend that both of these arguments are mistaken. Clinical equipoise provides erroneous ethical guidance in the case of placebo-controlled trials, because it ignores the ethically relevant distinction between clinical trials and treatment in the context of clinical medicine and the methodological limitations of active-controlled trials. Placebo controls are ethically justifiable when they are supported by sound methodological considerations and their use does not expose research participants to excessive risks of harm.     

An Exploration of Stigma in the Lives of Sex Offenders and Heroin Abusers

Research was conducted on variations and commonalities of sexual offenders and heroin abusers and how they manage stigma in their everyday lives. Interviews with 13 sex offenders (SOs) and 44 heroin abusers (HAs) were conducted in New York City. Results suggest that both SOs and HAs disclose or conceal their stigmatized status based on their relationship to others and the situations in which they anticipate social condemnation. Both groups have formed intra-group hierarchies based on status, where child molesters and heroin abusers receive the most disdain. Some heroin abusers manage their stigma by engaging in behavior that we term redemptive passing, in which stigmatized individuals attempt to pass as non-stigmatized through deceptive means in order to make amends for prior harms they have caused. The stigmatization of sex offenders and heroin abusers has important implications for health, as members of these groups are less likely to seek treatment in order to distance themselves from their stigmatizing status.     

Government initiatives in autism clinical trials

Randomized clinical trials remain the most valid method of testing the efficacy and safety of treatments. While efforts to elucidate the genetic and neurodevelopmental bases of autism are underway, clinicians and families are in need of scientifically valid information on how to best treat patients with autism. The effectiveness of many interventions currently used in communities has not been adequately tested. Given the high public health relevance of autism treatment research and the low interest of the pharmaceutical industry in autism, the role of the National Institutes of Health in supporting this research is paramount. Among recently launched initiatives in autism clinical trials, there are the Research Units on Pediatric Psychopharmacology Autism Network and the network of centers for Studies to Advance Autism Research and Treatment. These and other government activities in the area of autism clinical trials are here briefly reviewed.     

当代感染性休克糖皮质激素治疗的若干问题探讨

糖皮质激素替代治疗目前是全身性感染和感染性休克治疗的主要手段之一。尽管理论上存在着相对性肾上腺功能不足和糖皮质激素抵抗,但是其具体机制和诊断手段并未充分廓清;同时感染性休克小剂量激素替代治疗也未能被最新的临床研究证实。有鉴于此,有必要针对激素替代治疗对预后影响进行更深入的基础与临床研究。     

Clinical Equipoise and Adaptive Clinical Trials

Ethically permissible clinical trials must not expose subjects to risks that are unreasonable in relation to anticipated benefits. In the research ethics literature, this moral requirement is typically understood in one of two different ways: (1) as requiring the existence of a state of clinical equipoise, meaning a state of honest, professional disagreement among the community of experts about the preferred treatment; or (2) as requiring an equilibrium between individual and collective ethics. It has been maintained that this second interpretation makes it mandatory to minimize the number of patients receiving the treatment that will eventually be shown to be inferior by the trial. This requirement has led to the development of adaptive trials, i.e., trials in which treatment allocation is determined by data accumulated during interim analysis. Many statisticians argue that in some circumstances—typically with potentially high benefits, as in the much discussed ECMO trial—adaptive design is the only ethically permissible experimental design. Nevertheless, some proponents of clinical equipoise argue that adaptive trials are neither ethically required nor permissible. More specifically, they argue that clinical trials using adaptive designs fail to meet the moral requirement of clinical equipoise, since these trials presuppose an epistemic state that is incompatible with a physician’s duty of care to her subjects. This paper emphasizes that the debate is to a large extent resting on an epistemological confusion. Specifically, I argue that this response conflates two different conceptions of statistical evidence (i.e., frequentist and Bayesian), and that recognizing this distinction elucidates an epistemological framework in which adaptive trials are both consistent with and recommended by the moral requirement of clinical equipoise.

     

OPIOID ABSTINENCE REINFORCEMENT DELAYS HEROIN LAPSE DURING BUPRENORPHINE DOSE TAPERING

A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non‐treatment‐seeking heroin‐dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing assessments at each thrice‐weekly visit during dose tapering; 10 of 12 lapsed to heroin use 1 day after discharge. The abstinence reinforcement group (n = 10) received $30.00 for each consecutive opioid‐free urine sample; this significantly delayed heroin lapse (median, 15 days).     

Uncertainty and the Ethics of Clinical Trials

A probabilistic explication is offered of equipoise and uncertainty in clinical trials. In order to be useful in the justification of clinical trials, equipoise has to be interpreted in terms of overlapping probability distributions of possible treatment outcomes, rather than point estimates representing expectation values. Uncertainty about treatment outcomes is shown to be a necessary but insufficient condition for the ethical defensibility of clinical trials. Additional requirements are proposed for the nature of that uncertainty. The indecisiveness of our criteria for cautious decision-making under uncertainty creates the leeway that makes clinical trials defensible.     

Unique Ethical Concerns in Clinical Trials Comparing Psychosocial and Psychopharmalogical Interventions

In recent years, there has been a particular emphasis placed on conducting randomized controlled trials (RCTs) that compare the relative efficacy of psychosocial and pharmacological interventions. This article addresses relevant ethical considerations in the conduct of these treatment trials, with a focus on RCTs with children. Ethical concerns, including therapeutic misconception, treatment preference, therapeutic equipoise, structure of treatments, and balancing risks versus benefits, are introduced through a clinical scenario and discussed as they relate to psychotherapy versus medication RCTs. In each case, suggestions are made for researchers seeking to minimize the impact of these ethical concerns on research participants.     

Time Limited Treatment and C. G. Jung's Analytical Psychology

Abstract

The work of C. G. Jung has been largely neglected in recent discussions of time-limited psychotherapy. Notwithstanding this state of affairs, this paper argues that much is to be gained from familiarity with Jung's view on treatment. A brief overview of Jung's general system of psychology is presented, and contrasts are drawn to the work of Freud. Several distinctive characteristics of Jung's view of the clinical process are then identified, and a discussion of the course of treatment is provided with a brief reference to a case of Jung's and to the author's experience working with gay men.     

Introduction to IARPP Plenary Panel,Toronto, June 2015

These brief remarks introduce the symposium on Power and Authority, with clinical material by Francesca Colzani and discussions by Irwin Hoffman, Susanna Federici Nebbiosi, and Gillian Straker. I am glad we have the opportunity in this symposium to discuss power and authority in the clinical situation, because while this subject has been a center of interest for relational psychoanalysts since the inception of the relational perspective, explicit attention has not been paid to the topic in the recent past. Yet power and authority are always present and always important in our activities—in every clinical session, every supervision session, and every page we write. This symposium is composed of an incisive and moving clinical report by Francesca Colzani, followed by discussions by Irwin Hoffman, Susanna Federici Nebbiosi, and Gill Straker.     

AEDs and psychotropic drugs in children with autism and epilepsy

The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in autism--are limited by lack of controlled clinical trials, the small number of subjects, the heterogeneity of the population studied, and the brief duration of most drug trials. Indeed, few controlled clinical trials using AEDs in autism, with or without seizures, have been conducted. Because some AEDs also have a positive effect on mood, the benefits that children with autism sometimes obtain from these medications may not be due to the treatment of the abnormal electrical activity or the seizures per se but to an effect on common neuronal systems responsible for both behavior and epilepsy. The relationship between epilepsy and autism, and specifically the effects that abnormal electrical activity may have on the developing brain, may provide some valuable insights into the type of studies that are needed to help us understand the pathophysiology of autism.     

Behavioral equipoise: a way to resolve ethical stalemates in clinical research

Randomized trials depend on clinicians feeling that they are morally justified in allowing their patients to be randomized across treatment arms. Typically such justification rides on what has been called "clinical equipoise"--when there is disagreement of opinion among the community of experts about whether one treatment is better than another, then physicians can ethically enter their patients into a clinical trial, even if individual physicians are not at equipoise. Recent debates over prominent studies, however, illustrate that controversy can be easily created rather than dispelled by trials, with many clinicians choosing not to use the proven therapy until they receive more convincing evidence of its superiority. In such situations, we propose that a new standard of equipoise be used to guide decisions about the ethical justifications for research trials--a standard of behavioral equipoise. Under behavioral equipoise, a trial is potentially justifiable if it addresses behavioral resistance to prior scientific evidence.     

Behavioural treatment of obsessional-compulsive patients in routine clinical practice

There is a paucity of information available about the extent to which findings from research studies of behavioural treatments can be generalised to routine clinical practice. The characteristics and treatment at a series of 36 patients with obsessional-compulsive disorders who were referred to a National Health Service Behaviour Therapy Clinic are described. It appears that the methods developed and evaluated in research trials have been incorporated into everyday clinical practice, with some modifications (e.g. less in vivo practice but more home task assignment). The outcomes reported in the research trials were replicated in the clinical setting, and were shown to be achieved economically in terms of therapist time.     

Purchase task sensitivity to drug and nondrug reinforcers in opioid-agonist treatment patients

The behavioral economics of substance abuse has been increasingly recognized as a method of determining the value of abused substances for individuals who use those substances. It has been hypothesized that such analyses could serve as a clinical tool and that demand functions can be targeted predictors for the level of intervention necessary. This study evaluated the sensitivity of a demand task in 2 patient groups in a medication assisted treatment program (methadone maintenance), those who had used opioids in the last 2 months and those who had not used opioids in at least 18 months. Demand for 7 drugs and a control was assessed using hypothetical purchase tasks. Participants maintaining long-term abstinence had significantly higher α (sensitivity to price) and lower Q₀ (intensity of demand) for heroin than participants who had recently used opioids. Further research is necessary to illustrate if treatment is responsible for this reduction in demand. If so, demand analyses may provide clinical utility as an aid for treatment planning or as a target for treatment.     

PILLS OR SKILLS FOR HYPERACTIVE CHILDREN

The controversial nature of drug treatment of hyperactivity, the incidence and sequelae of hyperactivity, and problems of differential diagnosis of hyperactivity versus aggression were discussed. The effects of psychostimulant medication and behavior therapy on hyperactive children were reviewed with regard to effects on their social and academic behavior. Both treatments have resulted in clear short-term changes in social behavior but neither long-term academic nor long-term social effects have been shown with either treatment. Short-term effects on academic behavior have resulted from behavioral interventions but not from psychostimulants. However, the interventions have been too brief to allow one to draw unequivocal conclusions about the clinical efficacy of behavioral treatments. Although there have been long-term evaluations of psychostimulant therapy, there have not been any evaluations of long-term behavioral treatment programs for hyperactive children. Given the salutary short-term effects of behavior therapy with hyperactive children, extended clinical trials of behavior therapy need to be conducted. Finally, specific directions are suggested for future research.     

A behavioural-pharmacological treatment of dually addicted patients

maintenance appears to be an effective means of treating narcotic addiction both because it blocks the effects of heroin and because patients are willing to accept methadone treatment. However, alcoholism has been found commonly to complicate methadone maintenance and to result in treatment failure. The regular ingestion of disulfiram, a drug which blocks ethanol metabolism, could provide a solution to this problem, but alcoholics tend not to persist in taking this drug, because unlike methadone it possesses no reinforcing properties. This paper describes a novel technique whereby the reinforcing action of methadone has been employed to maintain disulfiram-taking, and thus to arrest alcohol abuse and consequent treatment failure.