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.     

Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence

OBJECTIVE: Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence. METHOD: Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance. RESULTS: Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study. CONCLUSIONS: Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome.     

Vergleichsuntersuchung von Buprenorphin und Methadon im Rahmen der Erhaltungstherapie Opiatkranker

The efficacy of buprenorphine in opioid dependent patients (n = 20) was compared to methadone maintained subjects (n = 20) in a randomized comparison trial. Sublingual application of buprenorphine as an alternative synthetical opioid is being compared to methadone during a 24 week study period. A trend (p = 0.06) could be found in the retention rate of investigated patients being maintained on a mean dosage of 63 mg oral applicable methadone (racemat of L- and D-methadone) in comparison to the group on a mean dosage of 7.3 mg buprenorphine (sublingual tablets). The dropout-rate of 11 subjects at the end of the study in the buprenorphine group was higher when compared to the dropout-rate of 5 in the methadone group. There was no significant difference between the two groups over the treatment period in respect to additional consumption of opiates, benzodiazepines and cocaine as evaluated through urine toxicology. The result in regard to compliance over the study period demonstrates that methadone appears to be the more successful oral opioid (p = 0.04). Nevertheless, efficacy of buprenorphine in maintenance could be demonstrated in the remaining subjects, and further studies with higher daily doses and a higher number of subjects have to be performed.     

Recent advances in the treatment of opioid use disorders–focus on long-acting buprenorphine formulations

Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders (OUDs). Three long-acting buprenorphine depot or implant formulations are currently available for the treatment of OUDs: (1) CAM 2038 (Buvidal) for subcutaneous weekly and monthly application; (2) RBP-6000 (Sublocade™) as a monthly depot formulation; and (3) A six-month buprenorphine implant [Probuphine™]. The pharmacology, clinical efficacy and prospects of these medications are discussed.     

Recent advances in the treatment of opioid use disorders–focus on long-acting buprenorphine formulations

Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders (OUDs). Three long-acting buprenorphine depot or implant formulations are currently available for the treatment of OUDs: (1) CAM 2038 (Buvidal) for subcutaneous weekly and monthly application; (2) RBP-6000 (Sublocade™) as a monthly depot formulation; and (3) A six-month buprenorphine implant [Probuphine™]. The pharmacology, clinical efficacy and prospects of these medications are discussed.     

Buprenorphine augmentation improved symptoms of OCD,compared to placebo - Results from a randomized,double-blind and placebo-controlled clinical trial

BackgroundIn the search for new psychopharmacologic options in the treatment of obsessive-compulsive disorders (OCD), some findings suggested that augmentation with buprenorphine, a partial-opioid agonist used to treat opioid addiction, moderate acute pain and moderate chronic pain, is worthy of consideration. Accordingly, to explore this possibility further, a double-blinded, placebo-controlled clinical trial was performed.MethodA total of 43 patients (mean age: 34.41 years; SD = 6.58; 53.5% males) with refractory OCD and treated with SSRIs or clomipramine at therapeutic dosages were randomly assigned either to an adjuvant buprenorphine or to an adjuvant placebo condition. Patients completed the Yale-Brown-Obsessive-Compulsive Scale (Y-BOCS) at baseline, weeks 3, 9 and 12 (study completion). Buprenorphine (2–4 mg; sublingual) and placebo (tablets with identical shape, color, consistency, and scent) were given daily.ResultsSymptoms of obsessive-compulsive disorders decreased over time, but more so in the buprenorphine than in the placebo condition. Substantial improvements were observed up to week 3 and then 9. Response and partial response were observed in the buprenorphine at week 9 more than in the placebo condition. The advantage had disappeared by week 12.ConclusionsThe pattern of results suggests that adjuvant buprenorphine augmentation can reduce symptoms of obsessive-compulsive disorders after only three weeks, compared to a placebo. Adjuvant buprenorphine seems to accelerate symptom improvement.     

Effect of two different methods of initiating atomoxetine on the adverse event profile of atomoxetine

OBJECTIVE: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. METHOD: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve once-daily dosing and titration to 1.2 mg/kg/day over 3 days (fast/once daily, n = 234) and three involve twice-daily dosing and titration to a dose of 1.2 mg/kg/day over at least 2 weeks (slow/twice daily, n = 213). RESULTS: During the first 2 weeks of treatment, fast/once daily titration patients showed higher rates of spontaneously reported adverse events than patients in the slow/twice daily titration group. This included decreased appetite (14.3% versus 8.0%, p = .036) and somnolence (14.3% versus 4.2%, p < .001). Patients in the slow/twice daily group showed higher rates of headache (7.4% versus 16.9%, p = .003). Analysis of the studies' overall acute treatment phases revealed significantly higher rates in the fast/once daily group only for somnolence. No significant differences were seen in completion rates or reasons for discontinuation. CONCLUSIONS: When starting atomoxetine, the risk of adverse events within the first few weeks of treatment may be lower if patients are dosed twice daily and titrated to the 1.2 mg/kg/day total daily dose over the first week.     

每周1次氟西汀维持治疗广泛性焦虑症

目的：比较每周1次与每天1次氟西汀维持治疗广泛性焦虑症的临床疗效。方法：将64例已接受每天1次氟西汀治疗，且临床疗效已达显著进步或痊愈的广泛性焦虑症病人，随机分为研究组（31例）和对照组（33例），研究组前2周改为每周2次氟西汀治疗，第3周开始改为每周1次氟西汀治疗；对照组继续每天1次氟西汀治疗，疗程3个月。采用汉密尔顿焦虑量表（HAMA）和副反应症状量表（TESS）评定疗效和药物不良反应。结果：研究组仅1例失败而更改治疗方案，研究组与对照组维持治疗前后组内和组间HAMA评分比较都无显著差异。结论：经过急性期治疗临床症状已经好转的广泛性焦虑症病人，采用氟西汀每周1次的治疗方案，也可以维持原有疗效。     

Buprenorphine reduces alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system.

BACKGROUND: Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at micro-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors. METHODS: Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol. RESULTS: Similar to prototypical micro-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p < .01); in contrast, the two highest doses reduced it (p < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorphine (p < .001) but did not affect the inhibition of ethanol drinking induced by 3.0 mg/kg of buprenorphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 microg/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine. CONCLUSIONS: Buprenorphine has dualistic effects on ethanol drinking; low doses increase alcohol intake via stimulation of classic opioid receptors, whereas higher doses reduce it via activation of NOP receptors. We suggest that NOP agonistic properties of buprenorphine might be useful in the treatment of alcoholism.     

Buprenorphine and morphine produce equivalent increases in extracellular single unit activity of dopamine neurons in the ventral tegrnental area in vivo

Buprenorphine is a synthetic opioid proposed as a potential treatment for drug abuse. Although buprenorphine is widely considered to be a partial agonist at opioid receptors, little is known of its electrophysiological effects in the central nervous system. Because buprenorphine has been reported to have limited hedonic effects in humans, and since activation of the dopaminergic system is thought to be critical to the reinforcing effects of drugs, we compared the ability of buprenorphine and morphine to activate dopamine neurons. We report here that buprenorphine and morphine are equally effective in increasing the impulse flow of dopamine cells in the ventral tegmental area. Extracellular single unit activity was recorded from dopaminergic (DA) neurons in the ventral tegmental area (VTA) of chloral hydrate anethestized rats. Standard physiological and anatomical criteria were used to identify DA neurons. Systemic injection of buprenorphine (5–200 μg/kg, i.v.) and morphine (1–10 mg/kg, i.v.) produced equal magnitudes of activation in a similar subset of DA neurons in the VTA (buprenorphine: 173%; morphine: 164%). Unlike morphine, the activation by buprenorphine was not reversed by the opioid antagonist naloxone (50–100 μg/kg, i.v.), but this is consistent with the known pharmacodynamics of buprenorphine at opioid receptors. These studies demonstrate that acute administration of buprenorphine has morphinelike effects on the impulse activity of DA neurons. The implications for use of buprenorphine as a clinical treatment for drug abuse are discussed. © 1994 Wiley-Liss, Inc.     

Pharmacotherapy for opioid addiction in community corrections

Abstract

Pharmacotherapy for opioid addiction with methadone, buprenorphine, and naltrexone has proven efficacy in reducing illicit opioid use. These treatments are under-utilized among opioid-addicted individuals on parole, probation, or in drug courts. This paper examines the peer-reviewed literature on the effectiveness of pharmacotherapy for opioid addiction of adults under community-based criminal justice supervision in the US. Compared to general populations, there are relatively few papers addressing the separate impact of pharmacotherapy on individuals under community supervision. Tentative conclusions can be drawn from the extant literature. Reasonable evidence exists that illicit opioid use and self-reported criminal behaviour decline after treatment entry, and that these outcomes are as favourable among individuals under criminal justice supervision as the general treatment population. Surprisingly, there is no conclusive evidence regarding the extent to which pharmacotherapy impacts the likelihood of arrest and incarceration among individuals under supervision. However, given the proven efficacy of these three medications in reducing illicit opioid use and the evidence that, in the general population, methadone and buprenorphine treatment are associated with reduction in overdose mortality, the use of all three pharmacotherapies among patients under criminal justice supervision should be expanded while more data are collected on their impact on arrest and incarceration.     

Transdermal buprenorphine in the treatment of chronic pain

The transdermal matrix patch formulation of buprenorphine has been shown to be effective in managing moderate-to-severe cancer pain and severe pain unresponsive to nonopioid analgesics. Clinical trials have revealed that it is possible to switch from weak opioids or low doses of step III opioids to transdermal buprenorphine without any problems. With buprenorphine patches, the sublingual buprenorphine intake was dose-dependently reduced and was superior to placebo in this respect. The proportion of responders increased with the buprenorphine dose, and a higher proportion of patients receiving buprenorphine patches reported uninterrupted sleep for longer than 6 h compared with those receiving placebo. In a long-term, open, follow-up study in which the mean duration of treatment was 7.5 months, analgesia was rated as at least satisfactory by 90% of patients. Almost 60% of patients could manage their pain with one patch alone or with one additional sublingual tablet a day during the whole period of treatment, indicating a low incidence of tolerance development. The buprenorphine transdermal patch was assessed as user friendly by 94.6% of patients. In a postmarketing surveillance study, pain relief with transdermal buprenorphine was rated as good or very good by 70% of the responders. Postmarketing surveillance studies have shown that transdermal buprenorphine is also effective in the management of nociceptive and neuropathic pain, which some studies have shown to be relatively insensitive to mu-opioid analgesics, such as morphine. Transdermal buprenorphine was well tolerated. Most adverse events were either local reactions to the patch that generally subsided within 24 h or systemic events typical of treatment with opioid analgesics, such as nausea, vomiting and constipation.     

Buprenorphine and Naloxone for Heroin Dependence

The pharmacology of buprenorphine is unique because of its partial agonist profile at the mu-opioid receptor (ie, high affinity, low intrinsic activity and slow dissociation). This unique profile results in greater safety, less physical dependence, and greater flexibility in dose scheduling. Buprenorphine has been investigated in combination with the opioid antagonist, naloxone, with the goal of decreasing abuse, misuse, and diversion. When combined with naloxone in a sublingual tablet, buprenorphine has been shown to be effective 1) in retaining patients in treatment, 2) in reducing opioid use and craving, and 3) when dosed less-than-daily. The pharmacologic effects of buprenorphine are not altered by the addition of naloxone when administered to the population in an appropriate combination ratio. However, if taken intravenously by individuals dependent on short-or long-acting opioids a precipitated withdrawal syndrome is observed, which should reduce its abuse potential. This review discusses the rationale for development and evidence supporting the use of a buprenorphine/naloxone combination product. The buprenorphine/naloxone combination product should be considered for use in primary care office-based settings as a safe and effective treatment that is likely to increase the availability of agonist treatment for opioid dependence.     

Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: A retrospective study

The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2+/-8.9, 177 males-29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9+/-0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) (p=0.006, p<0.001, p<0.001, p=0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) (p=0.06, p=0.003, p=0.008, p=0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses (p<0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical non-experimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention.     

Role of mu, delta and kappa opioid receptors in ethanol-reinforced operant responding in infant rats

We recently observed that naloxone, a non-specific opioid antagonist, attenuated operant responding to ethanol in infant rats. Through the use of an operant conditioning technique, we aimed to analyze the specific participation of mu, delta, and kappa opioid receptors on ethanol reinforcement during the second postnatal week. In Experiment 1, infant rats (PDs 14-17) were trained to obtain 5, 7.5, 10, or 15% ethanol, by operant nose-poking. Experiment 2 tested blood ethanol levels (BELs) attained by operant behavior. In Experiment 3, at PDs 16-18, rats received CTOP (mu antagonist: 0.1 or 1.0mg/kg), naltrindole (delta antagonist: 1.0 or 5.0mg/kg) or saline before training. In Experiment 4, rats received nor-binaltorphimine (kappa antagonist: 10.0 or 30.0mg/kg, a single injection after completion of PD 15 operant training), spiradoline mesylate (kappa agonist: 1.0 or 5.0mg/kg; at PDs 16-18) or saline (PDs 16-18), before the conditioning. Experiments 5 and 6 assessed possible side effects of opioid drugs in locomotor activity (LA) and conditioned taste aversion (CTA). Ethanol at 7.5 and 10% promoted the highest levels of operant responding. BELs were 12-15mg/dl. In Experiment 3 naltrindole (dose-response effect) and CTOP (the lowest dose) were effective in decreasing operant responding. Nor-binaltorphimine at 10.0mg/kg and spiradoline at 5.0mg/kg also blocked ethanol responding. The effects of opioid drugs on ethanol reinforcement cannot be explained by effects on LA or CTA. Even though particular aspects of each opioid receptor require further testing, a fully functional opioid system seems to be necessary for ethanol reinforcement, during early ontogeny.     

"More is less": a retrospective study of haloperidol dosages in acute schizophrenia

With the background of a number of meta-analyses on the optimal neuroleptic dosages [1,2] the average daily dosage for the treatment of acute schizophrenic episodes recommended in the internal treatment guidelines of our psychiatric clinic was reduced from 24 mg to 15 mg haloperidol equivalent. In the present retrospective study it was investigated what effect this change in guideline had on the actual dosing behavior and on the efficacy and the side effect rate of the antipsychotic treatment. For this purpose all haloperidol treated patients of a two year interval prior to the change of the guideline (1987/88, n = 103) were compared with all treated of a two year interval (1991/92, n = 87) following it. RESULTS: The evaluation of the treatment data showed that the dosing guideline was adhered to and in 1991/92 on the average actually only 15 mg haloperidol were prescribed daily in acute schizophrenic episodes. The antipsychotic efficacy was just as good under this dosage as under the average daily dose of 24 mg haloperidol given in the preceeding interval; the average time in hospital was even reduced from 76 to 67 days. Under the lower daily doses an additional medication with biperiden was less often required. CONCLUSION: Average daily doses of 15 mg haloperidol appear to be at least equally as effective and more tolerable for the treatment of acute schizophrenic episodes than average daily doses of 24 mg haloperidol.     

Plasma concentrations of timiperone and its reduced metabolite in the patients on timiperone

Plasma levels of timiperone (TIM) and reduced timiperone (RTIM) were determined in 10 schizophrenic patients who were treated with TIM. Activities of ketone reductase in red blood cells (RBC) were assayed using TIM and haloperidol (HAL) as substrates. Plasma levels of TIM and RTIM ranged from 3.2 ng/mL to 9.5 ng/mL and from 1.7 ng/mL to 7.6 ng/mL, respectively, and approximately four-fold inter-individual variations in RTIM/TIM (0.37-1.43, 0.67 +/- 0.25) were observed. There were significant and positive correlations between plasma levels of TIM or RTIM with the daily doses of TIM (mg/kg body weight); TIM (ng/mL)= 19.5 x daily dose of TIM (mg/kg) + 1.3, r = 0.79, n = 18, P < 0.01; RTIM (ng/mL) = 13.1 x daily dose of TIM (mg/kg) + 0.7, r = 0.73, n = 18, P < 0.001). Given 0.3 mg/kg of TIM, a plasma level of TIM as 7.15 ng/mL was predicted, which is approximately 60% that of HAL. The activity of TIM reductase in RBC was determined as approximately 70% of HAL reductase in RBC, although the correlation between the activities of TIM reductase and HAL reductase in RBC was high (r = 0.98, n = 10, P < 0.001).     

A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial

OBJECTIVE: Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment. METHOD: This randomized controlled trial was undertaken 2004-2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs. RESULTS: Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms. CONCLUSIONS: A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.     

New and effective treatment of experimentally induced venous thrombosis with anti-inflammatory rPSGL-Ig

BACKGROUND: P-selectin antagonism decreases thrombosis and inflammation in animal models of venous thrombosis (VT) prophylaxis. This study defines results using a P-selectin receptor antagonist for VT treatment. METHODS: Eight juvenile baboons underwent 6 h of iliofemoral venous stasis to produce an occlusive VT. Two days later, animals were treated for 14 days with rPSGL-Ig, 4 mg/kg (n3), LMWH (n2) or saline (n3) and treatment continued weekly (rPSGL-Ig) or daily (LMWH, saline). The animals were examined and sacrificed 14 days after treatment initiation (n4) or on day 90 (n4). RESULTS: Percent spontaneous vein reopening revealed a significant increase (p <0.05) in the proximal iliac vein in rPSGL-Ig and LMWH animals compared to controls (62%, 70% vs 8%), without differences in inflammation. No anticoagulation, thrombocytopenia, or wound complications were found in rPSGL-Ig animals. At 90 days, recanalization with iliac vein valve competence was found in treated animals. CONCLUSIONS: rPSGL-Ig successfully treated established VT without anticoagulation.     

Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance

BACKGROUND: Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. METHODS: Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). RESULTS: Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. CONCLUSIONS: In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.