***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Rationale Buprenorphine may be a useful alternative option to methadone in addicts . Opioids can produce severe changes in the immune system . Objectives The objectives of this study are to compare the effect of sublingual buprenorphine and methadone on the immune system and to compare the two substances on the drying-out program compliance . Methods We studied 62 r and omized out patients for a period of 12 months . Subjects ( 55 males and 7 females ; mean age 25±4 years ; average history of heroin abuse being 2 years ) on maintenance treatment were assigned in two groups ( A and B ) . Methadone chloride ( medium dose 100 mg/day ) was administered to group A , whereas group B received sublingual buprenorphine ( 32.40±2.8 mg/day ) . Urine toxicological screening , plasma levels of TNF-alpha interleukin-1 , interleukin-beta , lymphocyte CD14 and a self-rating depression question naire were measured . Results Urine screening was negative for opiates in 17.6 % of group A and in 10.7 % of group B ( p<0.001 ; r=0.62 ) . Depression score was 62±2 in group A and 55±3 in group B ( p<0.01 ) . Cytokine and CD14 revealed higher concentrations both in groups A and B without significant differences ( p>0.05 ) between the two groups . Conclusions The effects of buprenorphine and methadone tested on the immune system were overlapping in our patients . The elevated cytokine levels observed may suggest that the two drugs stimulate immunologic hyperactivation of an immune system that was formerly inhibited by heroin . Furthermore , our data suggest that buprenorphine can be a valid alternative to methadone in maintenance treatment of chronic heroin abuse and referred a marked decline in depression 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 r and omized 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 r and omly 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 sample s 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 sample s 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 BACKGROUND Opioid maintenance treatment ( OMT ) is generally considered to reduce mortality in opiate dependents . However , the level of mortality reduction is still uncertain . This study investigates mortality reductions in an " intention-to-treat " perspective including all dropouts . The mortality reducing effects of OMT are examined both within treatment and post-treatment . The study separates overdose and total mortality reductions . METHODS The study is a prospect i ve cross-registry study with up to 7 years follow-up . All opiate dependents in Norway who applied for OMT ( a total of 3789 subjects ) were cross-linked with data from the death registry from Statistics Norway . Date and cause of death were crossed with date s for initiation and termination of OMT , and subjects ' age and gender . A baseline was established from the waiting list mortality rate . Intention-to-treat was investigated by analysing mortality among the entire population that started OMT . RESULTS Mortality in treatment was reduced to RR 0.5 ( relative risk ) compared with pre-treatment . In the " intention-to-treat " perspective , the mortality risk was reduced to RR 0.6 compared with pre-treatment . The patients who left the treatment programme showed a high-mortality rate  , particularly males . CONCLUSIONS OMT significantly reduces risk of mortality also when examined in an intention-to-treat perspective . Studies that evaluate effects of OMT only in patients retained in treatment tend to overestimate benefits . Levels of overdose mortality will influence the risk reduction . Cross-registry studies as the current one are an important supplement to other observational design s in this field Abstract Objective : To evaluate an experimental heroin maintenance programme . Design : R and omised trial . Setting : Outpatient clinic in Geneva , Switzerl and . Subjects : Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments . Intervention : Patients in the experimental programme ( n=27 ) received intravenous heroin and other health and psychosocial services .  Control patients ( n=24 ) received any other conventional drug treatment ( usually methadone maintenance ) . Main outcome measures : Self reported drug use , health status ( SF-36 ) , and social functioning . Results : 25 experimental patients completed 6 months in the programme , receiving a median of 480 mg of heroin daily . One experimental subject and 10 control subjects still used street heroin daily at follow up ( difference 44 % ; 95 % confidence interval 16 % to 71 % ) . Health status scores that improved significantly more in experimental subjects were mental health ( 0.58 SD ; 0.07 to 1.10 ) , role limitations due to emotional problems ( 0.95 SD ; 0.11 to 1.79 ) , and social functioning ( 0.65 SD ; 0.03 to 1.26 ) . Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences . There were no benefits in terms of work , housing situation , somatic health status , and use of other drugs . Unexpectedly , only nine ( 38 % ) control subjects entered the heroin maintenance programme at follow up . Conclusions : A heroin maintenance programme is a feasible and clinical ly effective treatment for heroin users who fail in conventional drug treatment programmes . Even in this population , however , another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids BACKGROUND The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence , but there are few long-term and placebo-controlled studies of its effectiveness . We aim ed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence . METHODS 40 individuals aged older than 20 years , who met DSM-IV criteria for opiate dependence for at least 1 year , but did not fulfil Swedish legal criteria for methadone maintenance treatment were r and omly allocated either to daily buprenorphine ( fixed dose 16 mg sublingually for 12 months ; supervised daily administration for a least 6 months , possible take-home doses thereafter ) or a tapered 6 day regimen of buprenorphine , thereafter followed by placebo . All patients participated in cognitive-behavioural group therapy to prevent relapse , received weekly individual counselling sessions , and su bmi tted thrice weekly supervised urine sample s for analysis to detect illicit drug use . Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat . FINDINGS 1-year retention in treatment was 75 % and 0 % in the buprenorphine and placebo groups , respectively ( p=0.0001 ; risk ratio 58.7 [ 95 % CI 7.4 - 467.4 ] ) . Urine screens were about 75 % negative for illicit opiates , central stimulants , cannabinoids , and benzodiazepines in the patients remaining in treatment . INTERPRETATION The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious , and should be added to the treatment options available for individuals who are dependent on heroin This study a ) compared the effects of buprenorphine versus methadone maintenance on benzodiazepine and alcohol use and b ) evaluated the prognostic significance of gender and psychopathology and their interaction with maintenance treatment . Eighty male and 36 female patients were r and omly assigned to daily sublingual buprenorphine ( 4 or 12 mg ) or oral methadone ( 20 or 65 mg ) . Maintenance medication was not associated with significant differences in alcohol or benzodiazepine use . Rates of abstinence from illicit opioids were significantly higher for females , within the buprenorphine 4-mg group , females also had significantly better retention , lower rates of opioid-positive urine sample s , and higher rates of abstinence from illicit opioids . Lifetime sedative dependence was associated with significantly better retention , decreased rates of cocaine-positive urine sample s , and increased rates of cocaine abstinence ; among buprenorphine- but not methadone-maintained patients , it was also associated with increased rates of abstinence from illicit opioids The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts . Forty‐five patients were r and omized to receive either sublingual buprenorphine or oral methadone under double‐dummy and double‐blind conditions to study the pharmacology of buprenorphine in a 90‐day detoxification protocol . The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication . No significant between‐group differences were seen on measures of treatment retention , drug use , or symptom report . During the hydromorphone challenge , methadone  attenuated opioid effects to a greater extent than did buprenorphine on both physiologic ( pupil constriction ) and self‐report measures . However , this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine . The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts BACKGROUND Expansion of access to effective treatments for heroin dependence is a worldwide health priority that will also reduce HIV transmission . We compared the efficacy of naltrexone , buprenorphine , and no additional treatment , in patients receiving detoxification and subsequent drug counselling , for maintenance of heroin abstinence , prevention of relapse , and reduction of HIV risk behaviours . METHODS 126 detoxified heroin-dependent patients , from an outpatient research clinic and detoxification programme in Malaysia , were r and omly assigned by a computer-generated r and omisation sequence to 24 weeks of manual-guided drug counselling and maintenance with naltrexone ( n=43 ) , buprenorphine ( n=44 ) , or placebo ( n=39 ) . Medications were administered on a double-blind and double-dummy basis . Primary outcomes , assessed by urine testing three times per week , were days to first heroin use , days to heroin relapse ( three consecutive opioid-positive urine tests ) , maximum consecutive days of heroin abstinence , and reductions in HIV risk behaviours over 6 months . The study was terminated after 22 months of enrolment because buprenorphine was shown to have greater efficacy in an interim safety analysis . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00383045 . FINDINGS We observed consistent , linear contrasts in days to first heroin use ( p=0.0009 ) , days to heroin relapse ( p=0.009 ) , and maximum consecutive days abstinent ( p=0.0007 ) , with all results best for buprenorphine and worst for placebo . Buprenorphine was associated with greater time to first heroin use than were naltrexone ( hazard ratio 1.87 [ 95 % CI 1.21 - 2.88 ] ) or placebo ( 2.02 [ 1.29 - 3.16 ] ) . With buprenorphine , we also recorded significantly greater time to heroin relapse ( 2.17 [ 1.38 - 3.42 ] ) , and maximum consecutive days abstinent than with placebo ( mean days 59 [ 95 % CI 43 - 76 ] vs 24 [ 13 - 35 ] ; p=0.003 ) ; however , for these outcomes , differences between buprenorphine and naltrexone were not significant . Differences between naltrexone and placebo were not significant for any outcomes . HIV risk behaviours were significantly reduced from baseline across all three treatments ( p=0.003 ) , but the reductions did not differ significantly between the three groups . INTERPRETATION Our findings lend support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public-health approach to reduce problems associated with heroin dependence This study was design ed to compare 
    Output:
    
MAIN RESULTS We include 31 trials ( 5430 participants ) , the quality of evidence varied from high to moderate quality .There is high quality of evidence that buprenorphine was superior to placebo medication in retention of participants in treatment at all doses examined .
AUTHORS ' CONCLUSIONS Buprenorphine is an effective medication in the maintenance treatment of heroin dependence , retaining people in treatment at any dose above 2 mg , and suppressing illicit opioid use ( at doses 16 mg or greater ) based on placebo-controlled trials .
However , compared to methadone , buprenorphine retains fewer people when doses are flexibly delivered and at low fixed doses .
If fixed medium or high doses are used , buprenorphine and methadone appear no different in effectiveness ( retention in treatment and suppression of illicit opioid use ) ; however , fixed doses are rarely used in clinical practice so the flexible dose results are more relevant to patient care .
Methadone is superior to buprenorphine in retaining people in treatment , and methadone equally suppresses illicit opioid use