Durability of treatment response to zolpidem using a partial reinforcement regimen: does this strategy require priming?

BACKGROUND: Previous research has shown that after one month of full dose nightly treatment with zolpidem (priming), subjects with chronic insomnia (CI) switched to intermittent dosing with medication and placebos were able to maintain their treatment responses. This approach to maintenance therapy is referred to as partial reinforcement. The present study sought to assess whether priming is required for partial reinforcement or whether intermittent dosing with placebos (50% placebos and 50% active medication) can, by itself, be used for both acute and extended treatment. METHOD: 55 CI subjects underwent a baseline evaluation (Phase-1) and then were randomized to one of two conditions in Phase-2 of the study: one month of (1) nightly medication use with standard-dose zolpidem (QHS [n = 39]) or (2) intermittent dosing with standard-dose zolpidem and placebos (IDwP [n = 16]). In Phase-3 (three months), the QHS group was re-randomized to either continued QHS full dose treatment (FD/FD) or to IDwP dose treatment (FD/VD). Treatment response rates and Total Wake Time (TWT = [SL + WASO + EMA]) were assessed during each phase of the study. RESULTS: In Phase-2, 77% (QHS) and 50% (IDwP) subjects exhibited treatment responses (p = 0.09) where the average change in TWT was similar. In Phase-3, 73% (FD/FD), 57% (FD/VD), and 88% (VD/VD) of subjects exhibited continued treatment responses (p = 0.22) where the average improvement in TWT continued with FD/FD and remained stable for FD/VD and VD/VD (p < 0.01). CONCLUSION: These results suggest that intermittent dosing with placebos can maintain effects but do not allow for the additional clinical gains afforded by continuous treatment.

Conditioned pharmacotherapeutic effects: a preliminary study.

OBJECTIVE: To test the hypothesize that psoriasis patients treated under a partial schedule of pharmacologic (corticosteroid) reinforcement would show less severe symptoms and relapse than those given the same amount of drug under standard conditions. Behavioral conditioning as an inherent component of many pharmacotherapeutic protocols has never been examined. METHODS: A double-blind, simple randomization intervention was conducted with 46 patients from California and New York. Initially, lesions were treated with 0.1% acetonide triamcinolone under standard treatment conditions. Thereafter, a Standard Therapy group continued on continuous reinforcement (active drug every treatment) with 100% of the initial dose; Partial Reinforcement patients received a full dose 25% to 50% of the time and placebo medication other times; Dose Control patients received continuous reinforcement with 25% to 50% of the initial dose. RESULTS: Severity of disease scores in California neither supported nor refuted the hypothesis. In New York, where there was no difference between Partial Reinforcement and Dose Control groups at baseline, partial reinforcement effected a greater reduction in lesion severity than Dose Control conditions and did not differ from Standard Therapy patients receiving two to four times more drug. For the entire population, the frequency of relapse under partial reinforcement (26.7%) was lower than in Dose Control patients (61.5%) and did not differ from full-dose treatment (22.2%). CONCLUSIONS: A partial schedule of pharmacotherapeutic reinforcement could maintain psoriasis patients with a cumulative amount of corticosteroid that was relatively ineffective when administered under standard treatment conditions. Conceivably, corticosteroid administration only one quarter or half as frequently as currently prescribed is sufficient to treat psoriasis. We posit, however, that these preliminary observations implicate conditioning processes in-and for the design of-regimens of pharmacotherapy.

Durability of treatment response to zolpidem with three different maintenance regimens: a preliminary study.

BACKGROUND AND AIM: At present, there is no consensus regarding how to medically manage chronic insomnia in the long term. The unstated standard of practice is for patients to use hypnotics intermittently. The present study aimed to compare a partial reinforcement strategy with nightly and intermittent dosing strategies for its potential as a maintenance therapy. METHODS: A mixed model was used in the study. One between-subjects factor: group (n = 4). One repeated-measures factor: time (12 weekly assessments). A total of 74 subjects with chronic Insomnia were treated with 10 mg zolpidem for 4 weeks. Treatment respondents were randomized to nightly dosing with 10 mg or 5 mg (QHS-10 and QHS-5), intermittent dosing with 10 mg (IDS-10 [3-5 days weekly]), or partial reinforcement dosing with 10 mg (PRS-10 [nightly pill use with 50% active medication and 50% placebos]) for 12 weeks. RESULTS: It was found, in compliant subjects (n = 55), that all four strategies evaluated maintained treatment response over time (ie, prevented or delayed relapse). For the subjects that remained in remission, the subjects in the intermittent dosing group (IDS-10) group exhibited poorer sleep continuity. CONCLUSIONS: While best considered a preliminary study, the present findings suggest that the partial reinforcement strategy may be a viable means toward maintaining treatment gains over time with less active medication.

Psychosocial factors and the response to influenza vaccination in older adults.

OBJECTIVE: We examined the influence of psychological state (depression, negative affect, perceived stress) and social support on pre- and post-vaccination response to influenza vaccine. METHODS: Venous blood was drawn from 37 nursing home residents before and following injection of the trivalent influenza vaccine (comprised of the New Caledonia (NC), Hong Kong (HK), and Panama (Pan) strains of flu). The Geriatric Depression Scale, Perceived Stress Scale, Positive and Negative Affect Schedule, and Multidimensional Scale of Perceived Social Support were completed following the initial blood draw. RESULTS: Social support and perceived stress were correlated with pre-vaccine antibody responses to two of the three vaccine components (HK and NC). Social support was negatively correlated with both pre- and post-vaccine titers to Pan. Depression, positive affect, and negative affect were not related to vaccine response. CONCLUSIONS: Perceived stress and social support influence the rate of decline of antibody titers to previous exposures to some strains of influenza occurring either naturally or via deliberate vaccination.

The placebo effect: why we should care.

Contrary to its definition, a placebo is far from an inert substance but carries meaningful responses that can mediate significant outcome results in pharmacotherapeutic studies. The advent of detailed studies and modern imaging techniques have provided the basis to understand the underlying mechanisms of the placebo effect, as well as its localization to determined brain centers. Designing clinical trials using principles of classical conditioning to mediate placebo effects may enhance treatment outcomes and provide novel pharmacotherapeutic modalities.

Psychosomatic medicine: the scientific foundation of the biopsychosocial model.

OBJECTIVE: This article presents major concepts and research findings from the field of psychosomatic medicine that the authors believe should be taught to all medical students. METHOD: The authors asked senior scholars involved in psychosomatic medicine to summarize key findings in their respective fields. RESULTS: The authors provide an overview of the field and summarize core research in basic psychophysiological mechanisms-central nervous system/autonomic nervous system, psychoneuroimmunology, and psychoendocrinology-in three major disease states-cardiovascular, gastrointestinal, and HIV virus infections. CONCLUSIONS: Understanding the core scientific concepts and research findings of psychosomatic medicine should provide medical trainees with a scientific foundation for practicing medicine within a biopsychosocial model of care.

Conditioned immunomodulation: research needs and directions.

Considering the brief time that psychoneuroimmunology has existed as a bona fide field of research, a great deal of data has been collected in support of the proposition that homeostatic mechanisms are the product of an integrated system of defenses of which the immune system is a critical component. It is now clear that immune function is influenced by autonomic nervous systems activity and by the release of neuroendocrine substances from the pituitary. Conversely, cytokines and hormones released by an activated immune system influence neural and endocrine processes. Regulatory peptides and receptors, once confined to the brain, are expressed by both the nervous and immune systems enabling each system to monitor and modulate the activities of the other. It is hardly surprising, then, that immunologic reactivity can be influenced by stressful life experiences or by Pavlovian conditioning.

The immunomodulatory effects of behavior

Evidence is presented indicating that behavioral conditioning techniques can be used to suppress and enhance antibody- and cell-mediated immune responses. Application of conditioning techniques in the pharmacotherapy of autoimmune disease in New Zeland mice resulted in a delay in the onset of lupus using a cumulative dose of immunosuppressive drug that was not, by itself, sufficient to alter the course of the autoimmune disease. Convesely, behavioral studies in lupus-proneMrl lpr (lpr and Mrl +/+ mice suggest further that immune status can influence behavior and that such behavior may serve to correct and immunologic dysregulation. Theses data are interpreted to indicate behavior can serve an immunomodulatory function.