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Biomedical subjects

R Schottenfeld

Publications and source records attributed to R Schottenfeld.

15 recordsLinked to original sources

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.

BACKGROUND: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. METHODS: This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. RESULTS: In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. CONCLUSIONS: Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Adult↗

Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

OBJECTIVE: This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. METHOD: A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. RESULTS: Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. CONCLUSIONS: Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

Adult↗

Regulation of arousal and attention in preschool children exposed to cocaine prenatally.

Four lines of evidence suggest a plausible link between prenatal cocaine exposure (CE) and specific effects on the mechanisms subserving arousal and attention regulation in infants and preschool-aged children. These are (1) the association of prenatal CE with alterations in monoaminergic system ontogeny; (2) neurobehavioral effects of prenatal CE in animals consistent with an enduring increased level of activity in response to novelty and inhibited exploration and altered responses to stress, suggesting overarousal in the face of novel/stressful situations and disrupted attention and exploration; (3) altered norepinephrine system function in cocaine-exposed human infants; and (4) neurobehavioral findings in infants and preschool-aged children suggestive of disrupted arousal regulation in the face of novelty, increased distractibility, and consequent impaired attention to novel, structured tasks. This paper summarizes findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool-aged children followed longitudinally since birth. Arousal regulation in the face of novel challenges is operationalized behaviorally as state and emotional reactivity and neurophysiologically as the startle response and heart rate variability. Across different ages and tasks, behavioral and neurophysiological findings suggest that prenatally cocaine-exposed children are more likely to exhibit disrupted arousal regulation. Because the regulation of arousal serves as a gating mechanism to optimize orientation and attention, arousal regulation has important implications for ongoing information processing, learning, and memory. Furthermore, impaired arousal regulation predisposes children to a lower threshold for activation of "stress circuits" and may increase their vulnerability to the developmentally detrimental effects of stressful conditions particularly when such children are also exposed to the chaotic environmental conditions often characterizing substance-abusing families.

Adult↗

Nonpharmacologic approaches to substance abuse treatment.

Familiarity with nonpharmacologic approaches to substance abuse treatment is critical for medical practitioners to act effectively to prevent the progression of substance use to medically harmful use, abuse, or dependence; to identify patients with substance use disorders and motivation behavioral changes; and to maximize the likelihood of successful treatment. At their most basic level, these nonpharmacologic approaches involve components of practice that are requisite to the successful management of any medical disorder: fostering an empathic, supportive relationship; routinely evaluating the system or problem area; providing accurate medical information about diagnosis, natural history, and treatment; and following up on identified problems to improve compliance, evaluate the impact of treatment, and modify treatment as indicated. Because of the nature of substance use disorders, their impact on multiple areas of functioning, and the conditioned craving that occurs following repeated substance use, nonpharmacologic treatments can improve outcome, even when effective pharmacologic treatments are also employed. Treatment of nicotine dependence provides a useful example. Physician advice to stop smoking substantially increases the likelihood of smoking cessation and long-term abstinence. Combined with physician advice, nicotine replacement therapies, using nicotine gum or transdermal preparations, approximately double the rate of long-term abstinence, compared with physician advice alone. Providing behavioral treatment in addition to physician advice and nicotine replacement treatment leads to the highest rates of sustained abstinence, significantly higher than advice alone or rates associated with nicotine replacement alone. Nonpharmacologic treatments complement pharmacologic approaches often by addressing different target symptom and problem areas. In the case of nicotine dependence, nicotine replacement ameliorates withdrawal symptoms and craving associated with withdrawal. Behavioral treatment improves outcome by focusing on cue-evoked craving and developing effective long-term strategies to avoid or cope with craving and other cues. As discussed in this article, brief motivation approaches are particularly well suited for general medical practice settings. These approaches have been evaluated most extensively and shown to be most effective in preventing the progression of heavy drinking to problem drinking and alcohol dependence. Following a thorough evaluation of a patient's drinking habits, providing advice about sensible and safe drinking to patients identified as heavy drinkers leads to meaningful reductions in drinking. For patients who have developed problems of abuse or dependence, motivation approaches can be used to foster an interest and commitment to stop use and accept a referral to treatment. This article also provides an overview of the major psychosocial approaches used in more intensive specialty treatment of patients with substance use disorders. Familiarity with these approaches is essential for clinicians in general medical settings to facilitate referral of patients and monitor and improve the efficacy of treatments provided to patients. Medical practitioners must be able to educate patients about the need for more intensive specialty treatment and about what treatment entails. Medical practitioners must also be able to engage in informed discussions with substance abuse treatment specialists about the specific treatment recommendations made for a patient and the rationale for them. Medical practitioners who are informed about the treatment plans, rationale for treatment, and patient progress can play critical roles in encouraging patients to persist with the often difficult process of treatment.

Adaptation, Psychological↗

Six-month follow-up of naltrexone and psychotherapy for alcohol dependence.

BACKGROUND: The goal of this study was to examine the persistence of naltrexone's effects on drinking outcomes among alcoholics following discontinuation of treatment and to determine whether coping skills therapy improves long-term outcomes compared with supportive therapy. METHODS: Eighty of 97 alcohol-dependent subjects randomized to receive naltrexone or placebo and either coping skills therapy or supportive therapy for 12 weeks were assessed at a 6-month off-treatment follow-up. RESULTS: Subjects who received naltrexone were less likely to drink heavily or to meet criteria for alcohol abuse or dependence than subjects who received placebo. The effect of naltrexone therapy on abstinence rates persisted only through the first month of follow-up. Coping skills therapy was associated with decreased levels of drinking among subjects who received placebo. Psychotherapy condition, however, did not predict alcohol diagnosis at follow-up. CONCLUSIONS: Some but not all of the benefits resulting from short-term naltrexone treatment persist after discontinuation of treatment. The findings suggest that continued treatment with naltrexone may be beneficial for some patients.

Adaptation, Psychological↗

Cocaine-abusing parturients undergoing cesarean section. A cohort study.

BACKGROUND: Cocaine use in the United States is prevalent among pregnant women from inner city neighborhoods. To determine the anesthetic implications of cocaine use in parturients undergoing cesarean section delivery, the authors conducted a cohort study. METHODS: One thousand nine hundred seven women presenting for prenatal care were interviewed regarding substance abuse. Urine was analyzed for benzoylecgonine, tetrahydracannabinol, benzodiazepines, and opioids. Next all parturients who underwent cesarean section delivery were identified and their records reviewed for anesthetic and obstetric outcomes. RESULTS: Among the 51 women who were classified as cocaine abusers, the most frequent reasons for cesarean section were fetal distress (48%) and abruptio placenta (21%). In a multivariate model, cocaine abuse before delivery was shown to be an independent predictor of preoperative diastolic hypertension (F = 10.6, P = 0.01). Similarly, univariate analysis showed that immediately after intubation, diastolic blood pressure was significantly higher among parturients who used cocaine (99 +/- 13 mmHg v. 87 +/- 18 mmHg; P = 0.02). In contrast, epidural anesthesia was associated with hypotension significantly more often among cocaine-abusing parturients (44% vs. 10%; P = 0.04). A higher rate of perioperative wheezing was reported among patients who abused cocaine (16% vs. 6%; relative risk = 2.7); this finding, however, did not persist in multivariate analysis. Operative blood loss was similar in all groups (P = NS), and no ventricular dysrhythmias or cerebrovascular or coronary ischemic episodes were reported in any of the parturients. CONCLUSIONS: Although cocaine-abusing parturients are at higher risk for interim peripartum events such as hypertension, hypotension, and wheezing episodes, there is no significant increase in rates of maternal morbidity or death.

Adult↗

Thrombocytopenia in pregnant women who use cocaine.

OBJECTIVE: Our purpose was to determine the prevalence of cocaine-associated thrombocytopenia. STUDY DESIGN: This cohort study was conducted in an inner-city prenatal center. A total of 1907 patients were screened by the Mother's Project, which is an intervention project for inner-city cocaine-abusing parturients. Platelet counts were grouped by illicit drug usage. RESULTS: Platelet counts were available in 37% (709) of subjects; there were no differences between subjects with available platelet counts and those without on illicit drug use or other demographic measures. Five groups were defined: drug-free group (n = 331), cocaine group (n = 104), cocaine and opiates group (n = 11), opiates group (n = 18), and other-drug group (n = 236). Nineteen subjects had a low platelet count (< 150 x 10(9)/L). The medical records of all subjects with a low platelet count were reviewed for any medical condition known to be associated with thrombocytopenia, and two subjects were excluded. The rate of thrombocytopenia in the drug-free group was 1.5%, whereas the rate in the cocaine group was 6.7% (relative risk 4.4, p < 0.05). Because of the reported association of thrombocytopenia with seropositive human immunodeficiency virus status, seropositive women were excluded from the analysis. Even after human immunodeficiency virus status adjustments for the estimated rate, the cocaine-using group continued to have a significantly higher rate of thrombocytopenia (5.4% to 7.2% vs 1.23% to 1.26%, p < 0.05 to p < 0.005). CONCLUSIONS: These results indicate that cocaine use is an independent risk factor for thrombocytopenia in an inner-city parturient population.

Adult↗

Buprenorphine versus methadone maintenance for opioid dependence.

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neurobehavioral profiles of neonates exposed to cocaine prenatally.

This study examined the effects of maternal cocaine use on performance on the Neonatal Behavioral Assessment Scale (NBAS). Cocaine-exposed newborns (n = 56) were compared with a non-cocaine-exposed group (n = 30) born to mothers with similar sociodemographic characteristics. Cocaine-exposed newborns showed significant reduction in birth weight but did not experience greater obstetric or postnatal complications. On neurobehavioral assessments using the NBAS, cocaine-exposed newborns showed significantly depressed performance on the habituation cluster but not on other NBAS clusters when differences in birth weight were controlled. In a sample of 30 cocaine-exposed newborns matched on birth weight, gestational age, and race to the 30 non-cocaine-exposed newborns, cocaine-exposed newborns continued to show depressed habituation performance. The significance of a selective effect of cocaine exposure on early habituation performance is discussed in terms of the implications for attentional regulation in the first year of life.

Adult↗

Treatment of dual diagnosis patients: a relapse prevention group approach.

The authors describe the successful use of an adjunctive group psychotherapy for substance-abusing patients with major psychiatric disorders (bipolar, schizophrenia, schizoaffective, psychotic depression, and atypical psychosis). The group utilizes a psychoeducational approach that focuses on substance abuse causes and consequences, principles of recovery, and relapse prevention strategies. Eight patients with prolonged histories of abuse of cocaine, alcohol, marijuana, or other drugs were enrolled in this weekly group treatment at a community mental health center drug treatment program, while continuing in treatment with their current case manager or primary therapist. Six of the eight patients achieved periods of stable abstinence, documented by self-report, urine toxicology screens, continued group attendance, and improved social functioning. Case examples are utilized to illustrate the group process.

Adult↗

Buprenorphine for cocaine and opiate dependence.

Buprenorphine, a mixed opioid agonist/antagonist, has been examined not only for the treatment of opioid dependence, but also for concurrent dependence on both opioids and cocaine. Preliminary human studies have suggested that buprenorphine treatment may be associated with significantly less cocaine abuse than is treatment with methadone maintenance. Preclinical studies in both primates and rodents have also indicated that buprenorphine may reduce cocaine self-administration and attenuate place preference for cocaine. Two double-blind, randomized clinical trials comparing buprenorphine with methadone have failed to demonstrate that buprenorphine is superior to methadone in reducing cocaine abuse. However, the trial by Kosten and associates has suggested a larger reduction in cocaine abuse at 6 mg than at 2 mg daily of buprenorphine. This dose dependence is consistent with cocaine challenge studies in which buprenorphine attenuated cocaine effects at 4 mg, but not at 2 mg, daily.

Buprenorphine↗

Desipramine, amantadine, or fluoxetine in buprenorphine-maintained cocaine users.

The clinical efficacy of promising cocaine anti-craving medications was examined in combination with buprenorphine. Twenty-one opioid-dependent cocaine abusers were enrolled in a double-blind, 12-week trial in which they received on a daily basis buprenorphine (8 mg, s.l.) plus either desipramine (150 mg, p.o.), amantadine (300 mg, p.o.), or fluoxetine (60 mg, p.o.). Urine samples and self-reported drug use were obtained 1-3 times/week. The order of greatest patient retention across the 12 weeks was desipramine (83.3%) > amantadine (66.7%) > fluoxetine (20.0%). The desipramine and amantadine groups appeared to have greater increases in opioid- and cocaine-free urines than the fluoxetine group. These results suggest that desipramine and amantadine may facilitate greater opioid and cocaine abstinence than fluoxetine.

Adult↗