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.     

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Substance Use and Related Disorders. Part 2: Opioid dependence

Abstract

Objectives. To develop evidence-based practice guidelines for the pharmacological treatment of opioid abuse and dependence. Methods. An international task force of the World Federation of Societies of Biological Psychiatry (WFSBP) developed these practice guidelines after a systematic review of the available evidence pertaining to the treatment of opioid dependence. On the basis of the evidence, the Task Force reached a consensus on practice recommendations, which are intended to be clinically and scientifically meaningful for physicians who treat adults with opioid dependence. The data used to develop these guidelines were extracted primarily from national treatment guidelines for opioid use disorders, as well as from meta-analyses, reviews, and publications of randomized clinical trials on the efficacy of pharmacological and other biological treatments for these disorders. Publications were identified by searching the MEDLINE database and the Cochrane Library. The literature was evaluated with respect to the strength of evidence for efficacy, which was categorized into one of six levels (A–F). Results. There is an excellent evidence base supporting the efficacy of methadone and buprenorphine or the combination of buprenorphine and naloxone for the treatment of opioid withdrawal, with clonidine and lofexidine as secondary or adjunctive medications. Opioid maintenance with methadone and buprenorphine is the best-studied and most effective treatment for opioid dependence, with heroin and naltrexone as second-line medications. Conclusions. There is enough high quality data to formulate evidence-based guidelines for the treatment of opioid abuse and dependence. This task force report provides evidence for the efficacy of a number of medications to treat opioid abuse and dependence, particularly the opioid agonists methadone or buprenorphine. These medications have great relevance for clinical practice.     

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.     

Detoxification of opiate addicts with multiple drug abuse: a comparison of buprenorphine vs. methadone

Over the last few years, there has been a growing tendency for opioid addicts to abuse multiple drugs, although many patients are in substitution therapy with methadone. Abuse of multiple drugs leads to a more complicated withdrawal syndrome; it is therefore necessary to investigate new drug strategies as a treatment for detoxification. Buprenorphine appears to be an effective and safe drug in opioid-addicted patient detoxification. In this study, we have compared the short-term efficacy of an 11-day low-dose buprenorphine/14-day carbamazepine regime [BPN/CBZ] (n = 14) to an 11-day methadone/14-day carbamazepine regime [MET/CBZ] (n = 12) in a double-dummy, randomized 14-day inpatient detoxification treatment study. Twenty-six inpatients met the DSM-IV criteria for opioid dependence and were included in this study. All patients abused various additional drugs. Fourteen of 26 patients (53.8 %) completed the study. Seven non-completers (seven of 12 = 58.3 %) were treated with methadone/carbamazepine and five non-completers (five of 14 = 35.7 %) received buprenorphine/carbamazepine, but the difference in the dropout rate was not significant. However, patients with buprenorphine/carbamazepine showed significantly fewer withdrawal symptoms after the first two weeks of treatment. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than methadone/carbamazepine in detoxification strategies for opioid addict with additional multiple drug abuse. No severe side effects occurred during treatment in either group.     

The place of detoxification in treatment of opioid dependence

PURPOSE OF REVIEW: This review summarizes current research on the management of opioid withdrawal and considers the selection of the approach in different situations. RECENT FINDINGS: The recent publication of three controlled trials makes firm conclusions about the relative effectiveness of newer approaches (antagonist-induced withdrawal under anaesthesia or with minimal sedation; buprenorphine) to the management of opioid withdrawal possible. SUMMARY: Antagonist-induced withdrawal under anaesthesia should not be pursued as it has an increased risk of life-threatening adverse events and has no additional benefits relative to antagonist-induced withdrawal under minimal sedation. Antagonist-induced withdrawal with minimal sedation is feasible and may be suitable for those who intend to enter antagonist-maintenance treatment with a clear commitment to abstinence and good support. Buprenorphine is suitable for quick withdrawal, supports transition to naltrexone maintenance treatment, is safe and effective in outpatient settings and can be extended into maintenance treatment if the detoxification attempt is unsuccessful. Adrenergic agonists (clonidine and lofexidine) remain an effective option for those who do not want to use an opioid and do not intend to transfer to naltrexone maintenance treatment, with lofexidine being preferable for outpatient settings. Through appropriate choice of approach, detoxification can be a gateway to multiple, long-term treatment options.     

Evidenced-based treatment of opioid-dependent patients.

OBJECTIVE: To provide an overview of treatment options for opioid-dependent patients. METHOD: We screened all published studies on the treatment of opioid dependence, with a special focus on systematic literature reviews, formal metaanalyses, and recent trials. RESULTS: Both clinical experience and neurobiological evidence indicate that opioid dependence is a chronic relapsing disorder. Treatment objectives depend on the pursued goals: crisis intervention, abstinence-oriented treatment (detoxification and relapse prevention), or agonist maintenance treatment. The high quality of solid evidence in the literature demonstrates that there are numerous effective interventions available for the treatment of opioid dependence. Crisis intervention, frequently necessary owing to the high overdose rate, can be effectively handled with naloxone. Abstinence-oriented interventions are effective for only a few motivated patients with stable living conditions and adequate social support. Agonist maintenance treatment is considered the first line of treatment for opioid dependence. Numerous studies have shown efficacy for methadone and buprenorphine treatment, while maintenance with other agonists is also becoming available to a greater extent. Maintenance treatment with diamorphine should be made available for the small group of treatment-resistant, severely dependent addicts. Other harm-reduction measures can serve to engage individuals with opioid addiction who are not in treatment. CONCLUSION: Opioid dependence is a chronic relapsing disease that is difficult to cure, but effective treatments are available to stabilize patients and reduce harm, thereby increasing life expectancy and quality of life.     

An open pilot study of zonisamide augmentation in major depressive patients not responding to a low dose trial with duloxetine: preliminary results on tolerability and clinical effects

Background

The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months.

Methods

Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period.

Results

No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology.

Conclusions

Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too.     

Buprenorphine does not aggravate ischemic neuronal injury in experimental focal cerebral ischemia

Buprenorphine has been increasingly used as maintenance therapy in opioid dependence as an alternative to methadone and other pharmacological therapies. However, available data suggest increased risk of cerebrovascular events in opioid-dependent patients. Therefore, an opioid that provides safety with regard to neurological function should be considered by opioid-dependent patients. The evidence for the in vitro neurotoxic effects of buprenorphine is rapidly increasing. In order to clarify whether buprenorphine is also neurotoxic under the condition of cerebral ischemia in vivo, we applied an acute dose of buprenorphine in a transient model of focal cerebral ischemia in rats. Our study provides preclinical evidence for the usage of buprenorphine during the postoperative period following ischemic events as well as for the maintenance therapy of opioid-dependent patients wherein the risk of cerebrovascular events is increased.     

Psychopharmacologic treatment of borderline personality disorder

The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients'' overall functioning.     

Buprenorphine in pregnancy

The treatment of opioid dependence during pregnancy is a major challenge for doctors, social workers and gynaecologists. Continuous drug abuse during pregnancy can lead to a variety of complications in the mother, fetus and neonate. lt is recommended practice to maintain pregnant opioid-dependent women with synthetic opioids and according to international guidelines, methadone is the recommended substance so far. However, a neonatal abstinence syndrome (NAS) of varying severity is observed in 60 - 80 % of the neonates with even a longer course of duration in comparison to the NAS after heroin consumption during pregnancy. NAS is characterised by tremor, irritability, hypertonicity, vomiting, sneezing, fever, poor suckling, and sometimes convulsions. Recent studies have investigated the safety and efficacy of other synthetic opioids like sublingual buprenorphine for the treatment of pregnant patients. We present a 22 year old opioid-dependent woman, who has been maintained continuously on buprenorphine for 3 years. During the treatment episode she delivered two healthy newborns and both did not show any symptoms of NAS. The maintenance therapy with buprenorphine proved safety and efficacy during pregnancy, the mother was free of continuous heroin abuse, verified through supervised urine-toxicology. The quantitative and qualitative difference in NAS may be explained by the partial mu-receptor agonist and kappa-antagonist receptor profile of buprenorphine compared to pure mu-agonist action of methadone or heroin.     

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.     

Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome

A methadone maintenance patient with a decreased plasma methadone level, possibly due to phenobarbital-induced acceleration of methadone biotransformation, experienced opioid withdrawal symptoms. This finding suggests that when phenobarbital is used with methadone the plasma methadone level must be monitored.     

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.     

Valproic acid, unlike other anticonvulsants, has no effect on methadone metabolism: two cases

Two patients who were concomitantly undergoing methadone maintenance treatment and receiving phenytoin suffered continuing opioid withdrawal symptoms as a results of phenytoin's acceleration of methadone metabolism. When anticonvulsant therapy was discontinued, these patients had seizures. One patient was switched to carbamazepine as an alternative anticonvulsant, but this treatment resulted in a similar clinical problem. When both patients received valproic acid instead, the withdrawal symptoms disappeared and their conditions stabilized.     

Common genetic risk factors for psychiatric and simatic disorders

There is increasing knowledge about considerable comorbidity between psychiatric and somatic diseases, questioning whether variations in genes could be predisposing factors for both conditions. With respect to the multiple interactions between brain and body investigations have centered on variants in several candidate genes for proteins that mediate these interactions and therefore also have implications in psychiatric disorders. The available data, although still preliminary and rare, indicate the importance of polymorphic variants in genes coding for the serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT), the 5-HT(2A) receptor, proinflammatory cytokines, and the angiotensin-converting enzyme (ACE) in migraine, fibromyalgia, cardiovascular disorders, and psychiatric conditions. The role played by these various polymorphisms remains to be determined, as does whether they are indicative of common pathophysiological mechanisms or identify a subgroup of patients with somatic disorders that are more closely related to psychiatric symptoms. Nevertheless, they do at least illustrate the potential influence of genetic differences on illness course and treatment outcome, and might be a rational approach to drug development and treatment paradigms.     

The impact of subjective well-being under neuroleptic treatment on compliance and remission

The patients' perspective of antipsychotic treatment was largely neglected for a long period. It has only been during the last 10 years, with the development of atypical antipsychotics, that scientific interest in this issue has markedly increased. Numerous studies have shown that the majority of schizophrenic patients are able to fill out a self-rating scale in a meaningful way, and several self-report scales with sufficient internal consistency and good construct validity have been developed. The effects of antipsychotic treatment on psychopathology and on subjective well-being (SW) are not strongly related; the perspectives of the patient and his/her psychiatrist markedly differ. Recent research indicates that SW/quality of life, much more improved by atypical than by typical antipsychotics, has a strong impact on compliance, as well as on the chance of achieving remission. The data strongly suggest that a systematic evaluation of the patient's perspective of antipsychotic treatment is meaningful and necessary to increase compliance, functional outcome, and long-term prognosis.     

The pharmacological management of depression

Depressive disorders are common, recurrent, and chronic, and require treatment A review of the symptom picture and current drug targets demonstrates the need for accurate assessment of depression severity, including suicidality. The initial focus of treatment is rapid resolution of symptoms during an acute phase, followed by continuation. Maintenance treatment is indicated if the risk of recurrence is high. The range of available medications is considerable and the benefit/risk ratio is acceptable. Depression is diagnosable across the life span and treatable at every age (although recent disagreement has arisen with regard to young patients). Comorbidity, both psychiatric and medical, need to be assessed, as does the possible presence of two subtypes of depression (psychotic and bipolar) often requiring different interventions. It is expected that the next generation of antidepressants would be associated with more specific disease and outcome biomarkers.     

Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence

Research suggests that buprenorphine may possess antidepressant activity. The Beck Depression Inventory was completed at baseline and 3 months by heroin dependent subjects receiving either buprenorphine or methadone maintenance as part of a larger, pre-existing, double blind trial conducted by NDARC (Australia). Depressive symptoms improved in all subjects, with no difference between methadone and buprenorphine groups, suggesting no differential benefit on depressive symptoms for buprenorphine compared to methadone.