Predictors of self-reported discussion of cessation medications by physicians in New Jersey

Physicians play an important role in smoking cessation, especially discussing medications. This study evaluates physician characteristics associated with higher rates of discussion of smoking cessation medications. 336 primary-care physicians in New Jersey completed a cross-sectional, self-administered, mail survey including physician demographics, practice type, previous training and confidence in treating tobacco dependence, awareness of guidelines, and perceived effectiveness of treatments. Two-thirds of respondents felt confident in using cessation medications despite only 24% having previous training and only 13% having read or implemented practice guidelines. After controlling for other variables, female physicians were more likely to discuss medications compared with males (adjusted odds ratio(AOR) 2.2; 95% confidence interval(CI) 1.0-4.6); physicians who were confident were more likely to discuss (AOR 3.0;95% CI 1.7-5.3); and physicians in private practices (solo, group, or multispecialty) were more likely to discuss than those employed by an agency (hospital, state, or federal) (AOR 3.1;95% CI 1.4-6.8). Most physicians in this sample reported routinely discussing cessation medications, with female physicians, those feeling confident, and those in private practices doing so more frequently. Considering limited resources and opportunities to access physicians, interventions to increase discussion of effective cessation treatments could be targeted to specific physician groups.     

Craving as a predictor of treatment outcomes in heavy drinkers with comorbid depressed mood

Alcohol and depression comorbidity is high and is associated with poorer outcomes following treatment. The ability to predict likely treatment response would be advantageous for treatment planning. Craving has been widely studied as a potential predictor, but has performed inconsistently. The effect of comorbid depression on craving's predictive performance however, has been largely neglected, despite demonstrated associations between negative affect and craving. The current study examined the performance of craving, measured pre-treatment using the Obsessive subscale of the Obsessive Compulsive Drinking Scale, in predicting 18-week and 12-month post-treatment alcohol use outcomes in a sample of depressed drinkers. Data for the current study were collected during a randomized controlled trial (Baker, Kavanagh, Kay-Lambkin, Hunt, Lewin, Carr, & Connolly, 2010) comparing treatments for comorbid alcohol and depression. A subset of 260 participants from that trial with a Timeline Followback measure of alcohol consumption was analyzed. Pre-treatment craving was a significant predictor of average weekly alcohol consumption at 18 weeks and of frequency of alcohol binges at 18 weeks and 12 months, but pre-treatment depressive mood was not predictive, and effects of Baseline craving were independent of depressive mood. Results suggest a greater ongoing risk from craving than from depressive mood at Baseline.     

Neuropharmacological treatments for alcoholism: scientific basis and clinical findings

Preclinical studies have exploded our knowledge about the behavioral and biological underpinnings of alcoholism. These studies suggest that certain neurotransmitters, particularly those interacting with the opioid, N-methyl-d-aspartate, and monoamine systems, may play a critical role in the expression of alcohol-drinking and other behaviors associated with its abuse liability. Built upon this foundation, important advances have been made in the development of therapeutic medications for the treatment of alcoholism. Of the medications reviewed, acamprosate’s potential appears to be the most widely established. In the USA, naltrexone was approved by the Food and Drug Administration in 1995 for the treatment of alcoholism; however, the results of some studies have been less encouraging. Naltrexone’s reliance on high compliance rates for efficacy may, eventually, limit its potential in clinical settings offering generic treatment for alcoholism. The relative paucity of dose-response studies on naltrexone’s effects in treating alcoholics is an important gap in the literature. Recent data from a large clinical trial suggests that ondansetron, a serotonin₃ antagonist, offers new hope for the treatment of early onset alcoholics; a type of alcoholism most difficult to manage with psychosocial measures alone. Different subtypes of alcoholic may, therefore, have varying treatment responses to serotonergic agents. Matching subtypes of alcoholic to effective treatment medications based upon their different biologies remains an important therapeutic goal. Combinations of effective pharmacological agents need exploration as they may prove to be synergistic, and could shepherd in a new era of treatments aimed at multiple neurotransmitter targets associated with the alcoholism disease. The coming decade promises more powerful tools for characterizing drug effects on alcohol drinking, thereby closing the gap between animal models of addiction and the human condition. Received: 7 October 1999 / Final version: 23 December 1999     

Naltrexone treatment of comorbid alcohol and cocaine use disorders

 Naltrexone (NTX) has been shown to be efficacious for the treatment of alcohol dependence. Since alcohol and cocaine use disorders commonly co-occur, we conducted a randomized, double-blind, placebo-controlled trial of NTX 50 mg/day in 64 subjects with comorbid alcohol and cocaine use disorders. Although subjects in both groups reduced their consumption of both alcohol and cocaine during the 8-week trial, there was no consistent advantage to NTX over placebo treatment. We conclude that, due to behavioral, neurochemical, or other factors, individuals with both alcohol and cocaine use disorders are distinct from those dependent on alcohol alone, and that NTX at a dosage of 50 mg/day is not efficacious in this patient population. Several factors, including medication dosage, length of treatment, sample size and attrition rate, limit the interpretation of these findings. Consequently, we recommend that subsequent trials of NTX to reduce the risk of relapse in patients with comorbid alcohol and cocaine use disorders take these issues into account. Received: 15 November 1997 / Final version: 9 May 1998     

Advancing performance measures for use of medications in substance abuse treatment

Performance measures have the potential to drive high-quality health care. However, technical and policy challenges exist in developing and implementing measures to assess substance use disorder (SUD) pharmacotherapy. Of critical importance in advancing performance measures for use of SUD pharmacotherapy is the recognition that different measurement approaches may be needed in the public and private sectors and will be determined by the availability of different data collection and monitoring systems. In 2009, the Washington Circle convened a panel of nationally recognized insurers, purchasers, providers, policy makers, and researchers to address this topic. The charge of the panel was to identify opportunities and challenges in advancing use of SUD pharmacotherapy performance measures across a range of systems. This article summarizes those findings by identifying a number of critical themes related to advancing SUD pharmacotherapy performance measures, highlighting examples from the field, and recommending actions for policy makers.     

Acute effect of glucose tablets on desire to smoke

Rationale: Previous research suggests that glucose may reduce desire to smoke during periods of abstinence but a definitive test is needed. Objective: The present study aimed to determine whether a single administration of oral glucose would reduce desire to smoke in abstaining smokers. Methods: Thirty-eight smokers attended the laboratory in the afternoon having not smoked since the previous evening. They rated their desire to smoke immediately before and at 5-min intervals for 20 min after chewing four 3-g glucose tablets (experimental group) or four matched placebo tablets (control group). Results: Ratings of desire to smoke decreased to a greater extent in the experimental than the control group. The effect was apparent after 10 min. There was no difference between the groups in terms of feeling ”sick” or ”satisfied”. Conclusion: A single dose of glucose has a relatively rapid and detectable effect on desire to smoke and the effect is not mediated by feeling sick. Glucose tablets may be useful in helping to control desire to smoke during periods of abstinence. Received: 25 March 1999 / Final version: 9 July 1999     

Lack of effect of hydrocortisone treatment on d-fenfluramine-mediated prolactin release

 The prolactin responses to the serotonin (5-HT) releasing agent d-fenfluramine (30 mg orally) were studied in 11 male normal volunteers after administration of hydrocortisone (20 mg orally, twice daily for 10 days) using a double-blind, placebo-controlled, cross-over design. While hydrocortisone treatment significantly elevated 24-h urinary cortisol excretion, it did not lower the prolactin response to d-fenfluramine. Plasma levels of d-fenfluramine and d-norfenfluramine were not altered by hydrocortisone treatment. These findings show that following 10 days administration of hydrocortisone, the prolactin responses to d-fenflur amine are not changed. Received: 23 June 1997/Final version: 18 September 1997     

The effect of bupropion on nicotine craving and withdrawal

Rationale and objectives: Bupropion has demonstrated efficacy for smoking cessation. Given the importance of nicotine craving and withdrawal in the smoking cessation process, the current study examined the effects of bupropion on these parameters during smoking abstinence. Methods: During a 2-day Baseline phase with ad lib smoking, 91 non-depressed smokers (who were not trying to quit permanently) were administered measures of nicotine craving, withdrawal symptoms, and timed measures of cognitive performance five times daily. Participants were then assigned randomly to a 14-day treatment regimen with bupropion 300 mg/day, bupropion 150 mg/day, or placebo. Thereafter, the above measures were re-administered during 3 days of abstinence on a closed research ward. Results: Relative to placebo, 300 mg bupropion significantly reduced abstinence-associated increases in rated depression, difficulty concentrating, and irritability, and attenuated a decrease in positive affect. The results also suggested that bupropion might have a positive effect on performance measures during the withdrawal period. No effects were observed on craving, anxiety, restlessness, or hunger. The lack of findings on craving measures may be explained by a floor effect; except on the first day of abstinence, neither drug nor placebo groups showed much craving elevation during abstinence. Conclusions: Study results indicate that bupropion ameliorates some nicotine withdrawal symptoms. Received: 24 February 1999 / Final version: 15 August 1999     

Personality related effects of nicotine, mode of application, and expectancies on performance, emotional states, and desire for smoking

 Three separate factors relevant to nicotine effects have been investigated in this experiment in combination: the experimentally induced expectation about receiving a sham or a nicotine cigarette, the mode of application of nicotine by a tablet, by a cigarette or not at all, while the belief of receiving the nicotine via smoking was held constant in each condition (by nicotine or sham smoking), and the personality factors of extraversion or neuroticism, respectively. Ninety-six healthy female student smokers were tested in a 2 × 3 × 2 factorial group comparison design with respect to critical flicker fusion and reaction time performance as well as to self-ratings on emotional and cortical arousal and ratings on desire for further cigarettes (satisfaction from smoking a single cigarette containing either 0.8 mg nicotine or a sham cigarette). In each case, a tablet containing either nicotine or placebo was administered together with the cigarette. The results showed that performance is sensitive to interaction effects of instruction and mode of application. The instruction of sham or nicotine assignment when applied with a congruent treatment (sham with a sham cigarette, or nicotine with a nicotine cigarette) both increased performance, while groups with discordant information showed worse performance. The administration of nicotine by tablets or by smoking differs considerably, nicotine cigarettes causing a stronger increase in emotional arousal, tablets rather a decrease or no effect, while the true placebo condition increases arousal due to deprivation effects. This leads to an enhancement of the nicotine effect with real smoking and to reactive increase of effort when sham smoking. The instruction affects alertness, the nicotine illusion leading to a lower reduction in subjective reports of alertness and concentration than that observed with the sham instruction. Neurotic subjects become more anxious and tense with nicotine cigarettes than stable subjects. This effect is less pronounced or even reversed with tablets. No interactions with instructions are observed with neuroticism. Extraverts tend to show a decrease in performance but an increase in alertness with the instruction of receiving nicotine as opposed to the sham expectation, whereas introverts behave the opposite way. Subjective ratings on arousal seem to follow the law of transmarginal inhibition, with extraverts being pushed from low arousal to high and introverts vice versa by the mere expectation. Received: 11 February 1997/Final version: 30 June 1997     

Role of estradiol in puerperal psychosis

Rationale: The months following childbirth are a time when women are susceptible to depressive disorders, which may be severe and have long-lasting serious adverse consequences. The illnesses remain often unrecognized and untreated, and can be resistant to conventional psychiatric treatment methods. Objective: We report two patients with postpartum depression, who had low serum oestradiol together with psychiatric symptoms, and who responded successfully to treatment with oestradiol. Methods: The serum oestradiol concentration was measured at baseline and weekly during treatment with sublingual 17-β oestradiol for 8 weeks. The treatment effect was evaluated using the Montgomery-Åsberg Depression Rating Scale. Results: Both patients had a low pretreatment oestradiol concentration (36–120 and 31 pmol/l). During treatment with oestradiol, the decline of depressive symptoms coincided with a rise in serum oestradiol. Conclusions: Oestradiol may be causally related to postpartum depression and have significance in the treatment of this condition.     

治疗骨质疏松症的药物概述

骨质疏松是一种以骨密度和骨质量减低为特征的导致骨质松软、骨折危险性增加的疾病。骨质疏松和相关的骨折是导致死亡的重要原因。本文对目前正处在研究阶段的治疗骨质疏松症的药物进行了综述,包括骨吸收抑制剂,促进骨形成的药物及其他类。     

Mecamylamine blocks the development of tolerance to nicotine in rats: implications for the mechanisms of tolerance

 Chronic injections of nicotine in rats produce upregulation of nicotinic cholinergic receptors. It has been proposed that this upregulation is a reflection of receptor desensitization and is the basis of functional tolerance. Mecamylamine, a non-competitive antagonist that blocks activation of nicotinic receptors, does not prevent upregulation produced by nicotine injections. This suggests that receptor activation is not a prerequisite for nicotine-induced receptor upregulation. Therefore, the present experiments tested whether mecamylamine would also fail to prevent the development of tolerance to nicotine. Six daily pairings of mecamylamine (1 mg/kg SC) with nicotine did block the development of tolerance to nicotine-induced antinociception (0.35 mg/kg) and to the ability of nicotine to suppress milk intake (0.66 mg/kg). In another experiment, six daily injections of mecamylamine, when given alone, did not alter the effects of a subsequent, acute injection of nicotine (0.35 mg/kg) in inducing antinociception in rats. There was no evidence that after six pairings of mecamylamine with nicotine, the cues associated with mecamylamine delivery took on conditioned antagonistic properties. These findings suggest that, unlike the receptor upregulation that results from either continuous or repeated nicotine administration, the tolerance following a short series of intermittent nicotine injections is dependent on receptor activation. Received: 20 May 1998 / Final version: 23 July 1998     

Adenosine-dopamine interactions in the ventral striatum Implications for the treatment of schizophrenia

 The ventral striatum is included in brain circuits which connect brain areas classically ascribed to the motor or to the limbic system. In fact, the ventral striatum is involved in the connection between motivationally relevant stimuli and adaptive behaviours. Dopamine neurotransmission in the ventral striatum is essential for the increase in motor activity produced by motivational, salient, stimuli, such as food or novelty or by the administration of psychostimulants. Adenosine plays a role opposite to dopamine in the striatum and adenosine agonists produce similar behavioural effects as dopamine antagonists. On the other hand, adenosine antagonists, like caffeine, produce similar effects to increased dopaminergic neurotransmission in the striatum. Specific antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia play an essential role in the behavioural effects of adenosine agonists and antagonists. In particular, a strong antagonistic interaction between adenosine A_2A and dopamine D₂ receptors seems to take place in the striopallidal GABAergic neurons which originate in the ventral striatum. Therefore, adenosine A_2A agonists provide a potential new treatment for schizophrenia, since the dopamine D₂ receptors of the ventral striopallidal neurons appear to be involved in the antipsychotic effects of neuroleptics. In fact, in animal models, the adenosine A_2A agonist CGS 21680 has a profile of antipsychotic with a low liability to induce extrapyramidal side effects. Received: 10 March 1997 / Final version: 1 May 1997     

Pharmacological treatment of comorbid PTSD and substance use disorder: Recent progress

Previous research has identified a strong association between posttraumatic stress disorder (PTSD) and substance use disorder (SUD), necessitating the development of treatments that address both conditions. Some pharmacotherapies are effective for the treatment of PTSD and SUD alone, however; no medications have been proven to be effective for the combination of these conditions. We review the recent advances in pharmacological treatment of comorbid PTSD and SUD. A randomized clinical trial of sertraline, a serotonin reuptake inhibitor (SSRI), did not show overall efficacy for comorbid PTSD and alcohol dependence (AD), although it may have efficacy among light drinkers. Another clinical trial demonstrated the efficacy of both disulfiram and naltrexone for the treatment of AD in individuals with PTSD. A more recent clinical trial suggested that norepinephrine uptake inhibitors may also have efficacy for the treatment of comorbid PTSD and AD. In animal and preliminary human studies, brain norepinephrine and glutamate/GABA have emerged as potential treatment targets for comorbid PTSD and SUD. Noradrenergic medications that are promising for comorbid PTSD and SUD include prazosin, guanfacine, and atomoxetine. Promising glutamate/GABA medications include topiramate, memantine, acamprosate, N-acetylcysteine (NAC), and ketamine. The safety and efficacy of these medications for the treatment of PTSD and SUD need to be tested in controlled clinical trials.     

Sleep changes during long-term treatment of depression with fluvoxamine – a home-based study

Rationale: The effects of antidepressants on sleep in depression have been extensively investigated, although to date there have been relatively few studies of newer drug classes such as specific serotonin reuptake inhibitors (SSRIs). All reported studies on SSRIs have been conducted in patients admitted to sleep laboratories and very few longitudinal studies have continued to measure sleep beyond 5 weeks of treatment. The growing trend towards outpatient and community care has highlighted the need for studies of sleep in depression in a more naturalistic setting, and during longer periods of treatment in line with recommended clinical practice. Objectives: To establish if the changes in sleep architecture and continuity described during early treatment with SSRIs persist after 3 months, to relate these changes to clinical state, and to establish whether home recordings would yield similar results to previous laboratory studies. Methods: We have recorded objective sleep parameters in 12 depressed patients before and during 12-week treatment with an SSRI, fluvoxamine. All the sleep recordings were performed in the patients’ own homes, using the Oxford Medilog system. Results: At 12 weeks, 7/12 patients had responded (HAM-D decreased by >50%). REM latency showed the expected increase early in treatment; this change was less obvious at weeks 3 and 12. Amount of REM sleep was decreased at day 2 and week 3, but returned to baseline by week 12. Slow wave sleep was slightly increased at day 2 and decreased at week 12. Of the sleep continuity measures, the only significant change was in sleep onset latency, which was increased at week 3; the other measures showed non- significant worsening at night 2 and week 3, but most were better than baseline by 12 weeks. Subjective sleep (the three sleep items on the HAM-D) showed a progressive improvement over time, especially in the responders. Conclusions: The effects of the SSRI fluvoxamine on objective sleep measures are in the direction predicted by its pharmacological actions and some persist for at least 12 weeks. In addition subjective appraisal of sleep is strongly affected by mood state. All patients found the home recording procedure acceptable and only minimally disruptive. Received: 5 July 1999 / Final version: 22 November 1999     

A comparison of two depressive symptomatology measures in residential substance abuse treatment clients

Comorbid depression is common among substance abusers, making routine assessment of depression critical for high-quality care. We evaluated two of the most commonly used depressive symptomatology measures in a sample of clients (N = 240) in residential substance abuse treatment settings. The Beck Depression Inventory (BDI-II) has previously been used in clients receiving substance abuse treatment. The Patient Health Questionnaire (PHQ-9), originally developed for primary care settings, has not been used as frequently in substance abuse treatment settings, and it is unknown how it performs in this population. The measures were highly correlated with each other (r = .76) and demonstrated good internal consistency reliability (BDI-II = 0.91, PHQ-9 = 0.87); however, the PHQ-9 classifies more individuals as having “mild” depression symptoms relative to the BDI-II, which tends to suggest these individuals have no depression symptoms. Implications for assessing depression symptoms in individuals receiving substance abuse treatment are discussed.     

The effects of alcohol cues and an alcohol priming dose on a multi-factorial measure of subjective cue reactivity in social drinkers

Rationale: Exploring subjective alcohol cue reactivity in non-clinical samples should assist understanding in clinical samples where additional problems muddy the water. However, exploration is stalled through using insensitive, single-item representations. Objective: The effect of alcohol cues and a priming dose of alcohol on a new multi-factorial representation of cue reactivity is sought (DAQ, Desire for Alcohol Questionnaire). Methods: Prime and Cue exposure are variables in a standard 2×2 between subjects design set within a stooge taste-evaluation experiment. The DAQ was administered after a Prime and Cue exposure phase. Results: Main effects for Cue exposure but not Prime were found for the DAQ total and the subscales Mild desires (positively reinforcing items) and Strong desires/intentions but not Negative reinforcement (negatively reinforcing items) and Controllability; however, there was no interaction. Conclusion: The DAQ is a sensitive measure of subjective cue reactivity in social drinkers and its potential in the evaluation of pharmacological interventions is proposed. Received: 14 May 1999 / Final version: 4 June 1999     

Dopamine transporter and D2-receptor density in late-onset alcoholism

Rationale: Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect. Therefore, it is relevant to study both postsynaptic D₂-receptor and presynaptic dopamine transporter (DAT) densities among alcoholics. Objective: We investigated DAT densities, along with striatal and extrastriatal dopamine D₂-receptor densities, in nine non-violent late-onset male alcoholics, who had no major mental disorder nor antisocial personality disorder (ASPD), and nine healthy controls. Methods: [¹²³I]PE2I and [¹²³I]epidepride were used in SPECT imaging. Results: DAT occupancy ratios (striatum/cerebellum) were significantly lower among alcoholics than in controls. Extrastriatal D₂-receptor occupancy ratios (temporal pole/cerebellum) were not significantly different between the groups. Conclusions: Striatal presynaptic DAT densities are decreased among type 1 alcoholics, and this finding is not associated with recent alcohol abuse. Received: 22 March 1999 / Final version: 25 June 1999