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Heroin maintenance for chronic heroin dependents.

BACKGROUND: Dependent heroin users are characterised by the persistence of use in spite of the difficulties they experience with health, law, social achievements and personal relationships. The present review will consider maintenance treatment in which the patients enter programs of pharmacological administration tailored to achieve patient stabilisation. Many medications have been used for this purpose such as: Methadone, Buprenorphine and LAAM. The present review will focus on maintenance treatment through the prescription of heroin. OBJECTIVES: To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning. SEARCH STRATEGY: The Cochrane Central Register of Trials (CENTRAL) issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000 and CINAHL till 2000 were searched. There was no language or publication year restrictions. Many researchers were contacted for information. SELECTION CRITERIA: Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments. DATA COLLECTION AND ANALYSIS: The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity. MAIN RESULTS: 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies included could not be analysed cumulatively because of heterogeneity of interventions and outcomes considered. Two studies compared injected heroin to oral methadone for 1 year (270 patients) but considered different outcomes; one study compared injected heroin and methadone to oral methadone for 6 months (51 patients); and one compared inhaled heroin and methadone to oral methadone for 1 year (235 patients). Retention in treatment: in two studies there was no statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI 1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90) in favour of methadone. Relapse to illegal heroin use, based on self report: in one study the proportion of people still using heroin were 64% in the heroin group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72) in favour of heroin. The remaining studies did not provide the data. Criminal offence: one of the two studies which provided details about this showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome did not show statistical difference between intervention groups. The two most recent studies considered criminal offence and social functioning as part of a multidomain outcome measure and showed higher improvement among those treated with heroin plus methadone over those on methadone only. REVIEWER'S CONCLUSIONS: No definitive conclusions about the overall effectiveness of heroin prescription is possible because of non-comparability of the experimental studies available to be included in this review. Results favouring heroin treatment come from studies conducted in countries where the treatment system is comprehensive and easy accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments.

Heroin↗

Heroin dependence.

Heroin use, particularly injection use, is a problem of great public health importance. The risks associated with heroin dependence, such as HIV and viral hepatitis, and the social costs due to associated crime and poverty exceed those of most other drugs of abuse. Increasing purity and decreasing cost of heroin likely contribute to trends of decreasing age at first use and an increasing rate of initiation into regular use in the United States. Effective treatment is available for heroin dependence, so primary care providers should screen patients for this disorder. This article reviews the epidemiology of heroin use and dependence in the United States and outlines what is known regarding risk factors for initiation of heroin use and for heroin dependence.

Cost of Illness↗

The current status of heroin prescription treatment for heroin dependence.

Heroin prescription (HP) to treat severe heroin dependence has been available to few patients in the UK for several decades with limited, but generally favourable, evaluation. In the last decade, large trials have been reported from two countries, are presently underway in three other countries and under consideration in several other countries. The standard pharmacological treatments for heroin dependence, methadone and buprenorphine, attract and retain many more drug users than other pharmacological or nonpharmacological treatments and are strongly supported by evidence of efficacy, effectiveness, safety and cost effectiveness. On present evidence, HP is feasible and safe with limited, but increasing, evidence of efficacy and effectiveness. Although HP is more expensive than methadone, there is some evidence of cost effectiveness. HP is, at present, only considered a therapeutic option for a small minority of treatment refractory, severely heroin-dependent persons in developed countries with comprehensive treatment systems.

Clinical Trials as Topic↗

LAAM maintenance vs methadone maintenance for heroin dependence.

BACKGROUND: LAAM and methadone are both full mu opiate agonists and have been shown to reduce dependence on heroin when given continuously under supervised dosing conditions. LAAM has a long duration of action requiring dosing every two or three days compared to methadone which requires daily dosing. LAAM is not as widely available internationally as methadone, and may be withdrawn from the market following ten cases of life-threatening cardiac arrhythmias and an association with QT prolongation. OBJECTIVES: To compare the efficacy and acceptability of LAAM maintenance with methadone maintenance in the treatment of heroin dependence. SEARCH STRATEGY: We searched MEDLINE (January 1966 to August 2000), PsycINFO (1887 to August 2000), EMBASE (January 1985 to August 2000), and the Cochrane Controlled Trials Register (Issue 2 2000). In addition we hand searched NIDA monographs until August 2000 and searched reference lists of articles. SELECTION CRITERIA: All randomised controlled trials, controlled clinical trials and controlled prospective studies comparing LAAM and methadone maintenance for the treatment of heroin dependence and measuring outcomes of efficacy or acceptability were included. DATA COLLECTION AND ANALYSIS: Data on retention in treatment, heroin use, side-effects and mortality were collected by two reviewers independently. A meta-analysis was performed using RevMan. Discrepancies were resolved by consensus. MAIN RESULTS: Eighteen studies, (15 RCTs, 3 Controlled prospective studies) met the inclusion criteria for the review. Three were excluded from the meta-analysis due to lack of data on retention, heroin use or mortality. Cessation of allocated medication (11 studies, 1473 participants) was greater with LAAM than with methadone, (RR 1.36, 95%CI 1.07-1.73, p=0.001, NNT=7.7 (or 8)). Non-abstinence was less with LAAM (5 studies, 983 participants; RR 0.81, 95%CI 0.72-0.91, p=0.0003, NNT=9.1 (or 10)). In 10 studies (1441 participants) there were 6 deaths from a range of causes, 5 in participants assigned to LAAM (RR 2.28 (95%CI 0.59-8.9, p=0.2). other relevant outcomes, such as quality of life and criminal activity could not be analysed because of lack of information in the primary studies. REVIEWER'S CONCLUSIONS: LAAM appears more effective than methadone at reducing heroin use. More LAAM patients than methadone ceased their allocated medication during the studies, but many transferred to methadone and so the significance of this is unclear. There was no difference in safety observed, although there was not enough evidence to comment on uncommon adverse events.

Clinical Trials as Topic↗

Severity of heroin dependence and HIV risk. II. Sharing injecting equipment.

One of the most conspicuous risks of HIV transmission among drug injectors involves sharing injecting equipment which has been contaminated by infected blood. The present study investigates the relationship between severity of dependence upon heroin and the sharing of previously used injecting equipment (passive sharing). Four-hundred-and-eight heroin users were contacted and interviewed. Two-hundred-and-eighty-one (69% of the total heroin sample) had injected drugs on at least one occasion, and 204 of the 281 injectors (73%) had shared injecting equipment on at least one occasion after it had been used by someone else. The more severely dependent heroin injectors were more likely to have shared injecting equipment. As users become more dependent upon heroin, the types of factors which predispose them towards sharing may change. Less dependent users were more likely to use in public and 'social' settings, and they may be more likely to share injecting equipment with people they do not know well. The more dependent users appear to use heroin in private settings and to be at greater risk of sharing with dealers, perhaps because of the urgency of their need for drugs at times when they are in withdrawal. One of the most frequently cited reasons for sharing was that sterile injecting equipment was difficult to obtain. It is a matter for some concern that many of the sharers in our sample (24%) reported having shared used injecting equipment while in custody. There was good overall awareness of the risks of health problems associated with injecting among our subjects. However, awareness of risk was not associated with avoidance of sharing behaviour.

Adult↗

The medical management of adolescent heroin dependence.

The use of heroin by American adolescents is at its highest levels since the heroin epidemic of the 1960s. This clinical perspective reviews medical issues associated with adolescent heroin dependence. Older, as well as potential newer, treatments for adolescent heroin dependence are discussed. Multiple obstacles face a heroin-dependent adolescent who seeks treatment, including a lack of evidenced-based research on pharmacotheraputic agents for this population, strict restrictions on medications with demonstrated efficacy in adults, and a general lack of clinical experience in treating this population.

Adolescent↗

Pharmacologic treatment of heroin-dependent patients.

Patients with heroin dependence frequently present to internists and other physicians for heroin-related medical, psychiatric, and behavioral health problems and often seek help with reducing their heroin use. Thus, physicians should be familiar with the identification and diagnosis of heroin dependence in their patients and be able to initiate treatment of heroin dependence both directly and by referral. Recent research has provided much information concerning effective pharmacologically based treatment approaches for managing opioid withdrawal and helping patients to remain abstinent Methadone maintenance and newer approaches using L-alpha acetylmethadol and buprenorphine seem to be particularly effective in promoting relapse prevention. Although these treatments are currently provided in special drug treatment settings, recent and ongoing research indicates that the physician's office may be an effective alternative site for these treatments.

Analgesics, Opioid↗

Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials.

Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15-30 or 30-60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (d-amphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.

Adolescent↗

A pilot study of primary-care-based buprenorphine maintenance for heroin dependence.

The treatment of heroin dependence with opioid maintenance has traditionally employed methadone and more recently buprenorphine administered in traditional drug treatment settings. In this pilot study we evaluated buprenorphine maintenance for the treatment of heroin dependence in a program administered by primary-care providers in a primary-care setting. Seven patients were admitted to this nonblinded open-label pilot study and were offered 6 months of primary-care-based buprenorphine maintenance. Buprenorphine was administered in doses of 16 mg on Monday and Wednesday and 32 mg on Friday. Patients were seen weekly by primary-care providers and attended self-help meetings. Of the seven patients admitted to the study, five (71%) completed the 6-month pilot study and two (29%) were removed from the study. Urine toxicology data showed that the majority of urines tested were clear of opioids in four out of five patients who remained in treatment. These results suggest that primary-care-based opioid maintenance using buprenorphine shows promise as a new approach to the treatment of heroin dependence.

Adult↗

Personality and behavior patterns of heroin-dependent American servicemen in Thailand.

The authors compared a groups of heroin-dependent American servicemen stationed in Thailand with a matched control groups of men not dependent on heroin. The data gathered regarding social history, attitudes, work record, previous drug use, personality, and intelligence show significant differences between the heroin-dependent men and the control group in four areas: intelligence, work record, number of years of schooling and number of drug used before using heroin. The data suggest that many of the heroin-dependent men had difficulties related to a distant or negative relationship to their fathers; however, in contrast to previous studies of heroin addicts, they do not confirm a relationship between heroin dependence and any particular personality pattern.

Adolescent↗

Back-projection estimates of the number of dependent heroin users in Australia.

AIMS: To plan an appropriate response to heroin use in Australia, good estimates are needed of the numbers of dependent heroin users, the group who are most in need of treatment, most at risk of fatal opioid overdose and most at risk of contracting and transmitting blood-borne viruses. METHODS: Back-projection methods were used to estimate the numbers of people starting dependent heroin injecting in Australia between 1960 and 1997. Separate analyses were based on national opioid overdose deaths and numbers of new entrants to methadone treatment in New South Wales (NSW). Estimates of the rates at which dependent heroin users cease heroin use, commence methadone treatment or die from opioid overdoses were estimated from external data sources. RESULTS: Back-projection estimates derived from opioid overdose deaths indicated that there were 104 000 (lower limit of 72 000 and upper limit of 157 000) people who were heroin dependent in Australia between 1960 and 1997. Of these it was estimated that 67 000 (39 000-120 000) were still heroin dependent at the end of 1997. Back-projection estimates based on numbers of new entrants to methadone treatment in NSW indicated that there were 108 000 (82 000-141 000) heroin-dependent people in Australia between 1960 and 1997, of whom 71 000 (47 000-109 000) were estimated to be heroin dependent at the end of 1997. Both analyses indicated that the number of heroin-dependent people in Australia has increased substantially from the early 1970s onwards. CONCLUSIONS: Back-projection estimates based on analyses of treatment entries and opioid overdose deaths provide an additional method for estimating the numbers of heroin-dependent people in the population. The addition of these methods to existing methods, using different data sources and statistical methods, should improve consensus estimates of the numbers of heroin-dependent people.

Adolescent↗

[Study on the changes of ncNOS in chronic heroin dependence and spontaneous withdrawal in rats].

OBJECTIVE: To study the changes and actions of neuronal constructive nitric oxide synthase(ncNOS) in heroin drug abuse. METHODS: The expression of ncNOS and ncNOS mRNA in neurons of cerebral cortex, periaqueductal gray matter and the ventral tegmental area was observed by immunohistochemistry, in situ hybridization and image analysis technique after heroin dependence and spontaneous withdrawal in rats. RESULTS: The quantity of ncNOS and ncNOS mRNA rised clearly and the number of ncNOS and ncNOS mRNA positive cells increased greatly in heroin dependence and withdrawal. The changes of ncNOS and ncNOS mRNA in spontaneous withdrawal were more clear than ones of dependence. Heroin dependence and withdrawal led to alterations in ncNOS and ncNOS mRNA expression in important regions implicated in the physical tolerance and dependence. CONCLUSION: The ncNOS plays an important role in heroin dependence and withdrawal. The ncNOS immunohistochemical changes observed in the present study might be useful for the forensic pathological diagnosis of heroin drug abuse.

Animals↗

Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence.

Dopamine D4 receptor (DRD4) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution.

Adolescent↗

Differences in severity of heroin dependence by route of administration: the importance of length of heroin use.

To explore differences in the severity of heroin dependence by route of administration, we interviewed 909 heroin users in three Spanish cities. Dependence was measured with the severity dependence scale (SDS). No major differences in the severity of heroin dependence were detected among users with 5 or more years of heroin use (long-term users), but differences were found among newer users (SDS mean scores, 7.3 in heroin injectors; 7.9 in smokers and 4.6 in sniffers; P = 0.006), especially those with fewer than 3 years of use. Similar differences by route of administration were found when frequency of heroin use (days/month) was considered rather than severity of dependence. However, in the latter case major differences were also found among long-term users. These findings suggest that the route of administration probably influences the rate of progression to dependence but has little influence on the long-run level of dependence. They also help explain some aspects of the transition between routes of heroin administration, which is occurring in different areas.

Adolescent↗

The developmental outcome of children born to heroin-dependent mothers, raised at home or adopted.

In the present investigation we were interested to study the possible role of in-utero exposure to heroin and of the home environmental in the etiology of long-term developmental problems in children born to heroin-dependent parents in comparison to matched controls. The children were examined at .5-6 years of age by a developmental pediatrician and a developmental psychologist using, for the children up to 2.5 years of age, the Bayley Developmental Scales, and for children aged 3-6 years the McCarthy Scales for Children's Abilities. We examined 83 children born to heroin-dependent mothers, and compared the results to those of 76 children born to heroin-dependent fathers and to three control groups; 50 children with environmental deprivation, 50 normal children from families of moderate or high socioeconomic class, without environmental deprivation, and 80 healthy children from kindergartens in Jerusalem. There were five children (6.0%) with significant neurological damage among the children born to heroin-dependent mothers and six (7.9%) children among those born to heroin-dependent fathers. The children born to heroin-dependent mothers had a lower birth weight and a lower head circumference at examination when compared to controls. The children born to heroin-dependent parents also had a high incidence of hyperactivity, inattention, and behavioral problems. The lowest DQ or IQ among the children with cognitive levels above 70 was found in the children with environmental deprivation, next was the DQ or IQ of children born to heroin-dependent fathers, then the DQ or IQ of the children born to heroin-dependent mothers. When the children born to heroin-dependent mothers were divided to those that were adopted at a very young age and to those raised at home, the adopted children were found to function similarly to the controls while those not adopted functioned significantly lower. Our results show that the developmental delay and behavioral disorders observed among children born to drug-dependent parents raised at home may primarily result from severe environmental deprivation and the fact that one or both parents are addicted. The specific role of the in-utero heroin exposure in the determination of the developmental outcome of these children (if they do not have significant neurological damage), seems to be less important in comparison to the home environment.

Abnormalities, Drug-Induced↗

Gender effect on the right-left discrimination task in a sample of heroin-dependent patients.

RATIONALE: Discriminating right from left is an everyday cognitive ability. Repeated exposure to certain drugs, such as heroin, can produce poor performance on many cognitive tasks. However, it is yet unclear whether drug abuse impairs the ability of right-left discrimination. OBJECTIVES: The aim of the present study is to examine whether the spatial ability measured by the right-left discrimination task can be affected by heroin abuse and whether such drug effect, if it exists, is gender related. METHODS: A paper-and-pen test was used. The test consists of line drawings of a person with no arm, one arm, or both arms crossing the vertical body axis of the figure. The line drawings are viewed from the back, from the front, or randomly alternating between the back and front drawings. The subjects' task is to mark which is the right or left hand in the figure as fast as possible. RESULTS: A main finding in this study was that the ability to discriminate between left and right in visual space was impaired in heroin-dependent patients. Especially, heroin-dependent females performed poorer than control females in all conditions but heroin-dependent males only performed poorly in part of conditions. CONCLUSIONS: Recent heroin abuse impairs the ability of right-left discrimination and such impairment is gender related: heroin-dependent females demonstrated greater performance deficits than males.

Adult↗

[Association study of heroin dependence and catechol-O-methyltransferase gene].

OBJECTIVE: To detect the relationship between heroin dependence and catechol-O-methyltransferase (COMT) gene. METHODS: Genotype and allele frequencies of 108 val/met and 900 Ins C/Del C polymorphisms of COMT gene were examined in 313 heroin-dependent subjects and 214 normal controls. RESULTS: No differences in genotype and allele frequencies of 108 val/met polymorphism of COMT gene were observed between heroin-dependent subjects and normal controls (genotype-wise: chi-square=1.67, P=0.43; allele-wise: chi-square=1.23, P=0.27). No differences in genotype and allele frequencies of 900 Ins C/Del C polymorphism of COMT gene were observed between heroin-dependent subjects and normal controls (genotype-wise: chi-square=3.73, P=0.16; allele-wise: chi-square=0.76, P=0.38). CONCLUSION: The results suggested that neither 108 val/met polymorphism nor 900 Ins C/Del C polymorphism of COMT gene was associated with heroin dependence.

Adolescent↗