Buprenorphine and methadone maintenance in jail and post-release: a randomized clinical trial

Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting. This study introduced buprenorphine maintenance in a large urban jail, Rikers Island in New York City. Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10-90 days in jail (N=116) were voluntarily randomly assigned either to buprenorphine or methadone maintenance, the latter being the standard of care for eligible inmates at Rikers. Buprenorphine and methadone maintenance completion rates in jail were equally high, but the buprenorphine group reported for their designated post-release treatment in the community significantly more often than did the methadone group (48% vs. 14%, p<.001). Consistent with this result, prior to release from Rikers, buprenorphine patients stated an intention to continue treatment after release more often than did methadone patients (93% vs. 44%, p<.001). Buprenorphine patients were also less likely than methadone patients to withdraw voluntarily from medication while in jail (3% vs. 16%, p<.05). There were no post-release differences between the buprenorphine and methadone groups in self-reported relapse to illicit opioid use, self-reported re-arrests, self-reported severity of crime or re-incarceration in jail. After initiating opioid agonist treatment in jail, continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance.     

The practice of office-based buprenorphine treatment of opioid dependence: is it associated with new patients entering into treatment?

Office-based buprenorphine holds the promise of bringing patients who have never received pharmacotherapy into treatment. In a cross-sectional and longitudinal analysis, we compared patients entering a clinical trial of buprenorphine in a Primary Care Clinic (PCC) and those entering a local Opioid Treatment Program (OTP) and we compared the clinical characteristics and treatment outcomes of PCC patients with no history of methadone treatment (new-to-treatment) to those with prior methadone treatment. PCC subjects (N=96) were enrolled in a 26-week randomized clinical trial of office-based buprenorphine/naloxone provided in a PCC. OTP subjects (N=94) were enrolled in methadone maintenance during the same time period. PCC subjects compared with OTP subjects were more likely to be male (77% versus 55%, p<0.01), full-time employed (46% versus 15%, p<0.001), have no history of methadone treatment (46% versus 61%, p<0.05), have fewer years of opioid dependence (10 versus 15, p<0.001), and lower rates of injection drug use (IDU) (44% versus 60%, p=0.03). The new-to-treatment PCC subjects were younger (36 years versus 41 years, p=0.001), more likely to be white (77% versus 57%, p=0.04), had fewer years of opioid dependence (7 versus 14, p<0.001), were less likely to have a history of IDU (35% versus 54%, p=0.07), and had lower rates of hepatitis C (25% versus 61%, p=0.002) than subjects with prior methadone treatment. Abstinence and treatment retention were comparable in both groups. The results suggest that office-based treatment of opioid dependence is associated with new types of patients entering into treatment. Treatment outcomes with buprenorphine in a PCC do not vary based on history of prior methadone treatment.     

Effect of opioid substitution therapy on alcohol metabolism

Forty opioid substitution patients (methadone, n = 14; LAAM, n = 14; and buprenorphine, n = 12) who were participating in a study on the impact of opiate substitution treatment on driving ability and 22 non-opiate-using control subjects were administered 14.7 g/70 kg of alcohol in two separate sessions, one 2-3 hours before opioid pharmacotherapy dosing and the other 1-2 hours after dosing. The mean blood alcohol concentration (BAC) in the post-opioid dose session was significantly lower than that in the pre-opioid dose session (p < .05). There was a significant effect of experimental group (LAAM, methadone, buprenorphine, or control) on BAC in sessions conducted 1-2 hours after the opioid substitution dose (p < .01). There was a trend for a reduced effect of experimental group on BAC in the pre-opioid substitution dose session (p = .06). The BAC of non-opioid substitution control subjects was significantly higher than that of the LAAM (before and after LAAM dosing) and methadone (after methadone dosing; p < .05) patients. These findings provide evidence for the first time of an interaction between opiates and alcohol in humans that is strongest at the time of peak opiate plasma levels in the hours after opioid dosing.     

Association of OPRK1 gene polymorphisms with opioid dependence in addicted men undergoing methadone treatment in an Iranian population

Previous studies have shown significant associations between OPRK1 and susceptibility to opioid dependence and the relationships between libido dysfunction and insomnia among opium addicts who underwent methadone maintenance treatment. The authors investigated the single locus and haplotype association of rs997917, rs6985606, and rs6473797 with susceptibility to opioid addiction. Samples were selected among 202 healthy individuals and 202 opium addicts undergoing methadone maintenance treatment. Genomic DNA was extracted from the whole blood samples of all subjects through a salting out procedure. All three variants were genotyped in the studied subjects using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). The whole analysis process was performed using SNPAlyze and SPSS ver.20 software packages. According to the single locus analyses, rs997917 and rs6985606 represented significant associations with opium addiction under recessive (p = 0.0128) and co-dominant (p = 0.0001) inheritance models, respectively. The haplotypes C-T-C (Permutation p = 0.014) and C-T-T (Permutation p = 0.0002) were significantly associated with opioid dependence. Among methadone maintenance treatment individuals, rs997917 was significantly associated with insomnia in both allelic and genotypic levels (p = 0.0001 and p = 0.038, respectively). Furthermore, rs6985606 had the only significant association with the co-incidence of insomnia and libido dysfunction in the methadone maintenance treatment group (p = 0.038). The OPRK1 gene variants showed significant association with susceptibility to opioid dependence among Iranians.     

Trait impulsivity and cognitive domains involving impulsivity and compulsivity as predictors of gambling disorder treatment response

Background and aimsGambling disorder (GD) is a highly heterogeneous condition with high rates of chronicity, relapses and treatment dropout. The aim of this study was to longitudinally explore the associations between trait impulsivity, impulsivity-compulsivity related cognitive domains, and treatment outcome in an outpatient sample of adult patients with GD.Methods144 adult male participants diagnosed with GD undergoing cognitive-behavioural treatment (CBT) at a specialized outpatient service completed a series of neuropsychological tests to assess executive functioning (including cognitive flexibility, inhibition control and decision making) and psychometric questionnaires.ResultsTrait impulsivity predicted low compliance [UPPS-P negative urgency (B = 0.113; p = 0.019)] and relapse [UPPS-P negative urgency (B = 0.140; p = 0.015)] at 5 weeks of treatment and dropout at the end of treatment [(UPPS-P sensation seeking B = 0.056; p = 0.045)]. Cognitive flexibility performance predicted: dropout rates at the end of treatment [WCST perseverative errors (B = 0.043; p = 0.042)]; dropout [WCST categories completed (B = −1.827; p = 0.020)] and low compliance or relapses at follow-up [WCST perseverative errors (B = 0.128; p = 0.020)]; and time to first relapse [WCST failure to maintain set (B = −0.374; p = 0.048)] and time to dropout [WCST perseverative errors (B = 0.0198; p = 0.019)].ConclusionsOur findings indicate impulsivity-compulsivity levels may influence response to GD treatment (i.e.: low compliance and dropout or relapse rates) thus representing a potential target for improving treatment outcomes.     

盐酸齐拉西酮和氟哌啶醇对精神分裂症认知灵活性的疗效比较

目的:探讨比较盐酸齐拉西酮和氟哌啶醇对精神分裂症患者认知灵活性的疗效.方法:对50例服用齐拉西酮维持治疗与50例服用氟哌啶醇维持治疗的精神分裂症患者进行12个月随访,采用威斯康星卡片分类(WCST)和连线测验(Trailing Making)评估患者的认知灵活性.结果:维持治疗12个月末齐拉西酮组和氟哌啶醇组的WCST测验中的总分类次数、错误数、持续错误数、非持续错误数以及连线测验各指标(连线A、B时间,A、B错误数和A、B犯规数)均显著下降(P＜0.05),并且齐拉西酮组的持续错误数减分率显著高于氟哌啶醇组(P＜0.05).治疗后,两组连线测验成绩减分率差异无统计学意义(P＞0.05).结论:齐拉西酮较氟哌啶醇更有益于改善精神分裂症患者的认知灵活性.     

Comparative pharmacodynamics and pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of opioid dependence

BACKGROUND: Slow-release oral morphine (SROM) has been proposed as an alternative maintenance pharmacotherapy to methadone for treatment of opioid dependence. However, the pharmacodynamics and pharmacokinetics of SROM have not been previously assessed in a methadone maintenance population. METHODS: In 14 methadone maintenance patients reporting adequate (holders, n=7) or inadequate (non-holders, n=7) withdrawal suppression between doses, plasma drug concentrations and indices of opioid effect (withdrawal severity, pupil diameter, and respiratory rate) were determined across a 24 h inter-dosing interval on one occasion at steady-state for methadone and SROM (once-daily Kapanol) using an open-label, crossover design. RESULTS: Opioid effects were of a similar overall magnitude following dosing for each drug and showed an inverse association with plasma drug concentrations, which peaked later for morphine compared to (R)-methadone (6.5 +/- 2.3 h vs. 2.5 +/- 1.4 h, P<0.001). For methadone non-holders, the number of self-reported opioid withdrawal symptoms prior to dosing was less for SROM compared to methadone (3.4 +/- 2.6 vs. 9.0 +/- 3.2, P<0.01); for holders it was approximately equal (4.4 +/- 3.0 vs. 4.0 +/- 3.7, P<0.76). Maintenance doses were more strongly related to plasma drug concentrations for SROM compared to methadone and may thus be more predictive of therapeutic response for the former medication. Twelve of the 14 subjects preferred SROM to methadone (P=0.01). CONCLUSIONS: The pharmacodynamics and pharmacokinetics of SROM support its use as an alternative once-daily agonist option in the treatment of opioid dependence, particularly for patients responding poorly to methadone maintenance treatment.     

Opioid detoxification with buprenorphine,clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.     

A behavioral treatment for opioid-dependent patients with antisocial personality

Antisocial personality disorder (APD) is associated with increased problem severity in treatment-seeking opioid-dependent patients. Treatment studies have reported mixed results but generally show that patients with APD make progress that is often comparable to drug-dependent patients without the personality disorder. Much of this work is based on secondary analyses of studies evaluating responses to a variety of drug abuse treatment interventions. This study reports on a randomized prospective trial evaluating a behavioral approach for managing opioid-dependent patients with APD. Subjects (N = 100) met Diagnostic and Statistical Manual of Mental Disorders criteria for opioid dependence and APD using a structured clinical interview and were randomly assigned to either an experimental condition (n = 51), which used a highly structured contingency management intervention, or a control condition (n = 49), which reflected standard methadone treatment. Subjects in the experimental group had significantly better counseling attendance and some indication of lower psychosocial impairment compared to the control group. The experimental intervention increased attendance in subjects with low and high levels of psychopathy and with and without other psychiatric comorbidity. These findings support the development of interventions more tailored to drug-dependent patients with APD.     

An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans

Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44–0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95–2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population.     

Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy

Background:

Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS.

Methods:

Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects.

Results:

Significant reductions in N-acetylaspartate (NAA) and choline-containingCompound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group.

Conclusions:

Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.     

Prospective comparative assessment of buprenorphine overdose with heroin and methadone: Clinical characteristics and response to antidotal treatment

Buprenorphine is a partial opioid agonist with a “ceiling effect” for respiratory depression. Despite this, it has been associated with severe overdoses. Conflicting data exist regarding its response in overdose to naloxone. We compared clinical overdose characteristics of buprenorphine with heroin and methadone and assessed responses to naloxone and flumazenil. Patients admitted to two intensive care units with severe opioid overdoses were enrolled into this 4-year prospective study. Urine and blood toxicological screening were performed to identify overdoses involving predominantly buprenorphine, heroin, or methadone. Eighty-four patients with heroin (n = 26), buprenorphine (n = 39), or methadone (n = 19) overdoses were analyzed. In the buprenorphine group, sedative drug coingestions were frequent (95%), whereas in the methadone group, suicide attempts were significantly more often reported (p = .0007). Buprenorphine overdose induced an opioid syndrome not differing significantly from heroin and methadone in mental status (as measured by Glasgow Coma Score) or arterial blood gases. Mental status depression was not reversed in buprenorphine overdoses with naloxone (0.4–0.8 mg) but did improve with flumazenil (0.2–1 mg) if benzodiazepines were coingested. In conclusion, buprenorphine overdose causes an opioid syndrome clinically indistinguishable from heroin and methadone. Although mental status and respiratory depression are often unresponsive to low-dose naloxone, flumazenil may be effective in buprenorphine overdoses involving benzodiazepines.     

Higher maternal doses of methadone does not increase neonatal abstinence syndrome

Objective

The purpose of this study is to assess the incidence of clinically significant neonatal abstinence syndrome (NAS) based on maternal antenatal methadone dosing in women with a history of narcotic dependence.

Study design

A retrospective review of 174 pregnant women on methadone maintenance was performed. Data were stratified based on maternal methadone dose at delivery: low (0–50 mg/day, n = 59), medium (51–100 mg/day, n = 63), and high (>100 mg/day, n = 52). NAS was defined by Finnegan as score greater than 7 on two occasions. Outcome measures were rate and severity of NAS, birth weight, preterm birth rate, and neonatal morbidities and mortality.

Results

The rates of NAS (40.7% vs. 52.4% vs. 40.8%, p > .05), birth weight, and neonatal morbidities were similar regardless of the maternal methadone dose. Although there was a trend toward earlier delivery, the rate of preterm birth among the three groups (low dose, 17%; medium dose, 19%; high dose, 27%; p > .05) was not statistically significant.

Conclusion

Higher maintenance dosing of methadone is not associated with increased rate or severity of NAS or other adverse perinatal outcomes. Concerns about NAS should not restrict the methadone dosing during pregnancy. Methadone dosing should not be restricted to lower dosing during pregnancy.     

抑郁症患者与正常人认知功能评估的比较

目的 探讨抑郁症患者与正常人认知功能的差异;探讨抑郁患者抑郁症状和认知功能的相关性.方法 对110例新近发作或两周内未服用抗抑郁药物的抑郁症患者和114例正常成人进行了认知功能的对照性评估;抑郁症患者治疗前后认知功能的改变进行评估.结果 患者组WCST的分类数、总错误数均明显高于对照组(分类数:8.35±0.7,P=0.00;总错误数:7.60±2.8,P=0.00),对照组的正确数和分类数明显高于患者组(40.40±2.8,P=0.00).患者组中HAMD总分与WCST的分类数呈正相关,与分类数、正确数呈负相关,治疗前后HAMD总分、WCST的总测验次数、持续错误数、随机错误数比较均有显著性差异(P＜0.01).结论 抑郁症患者存在认知功能损害,其认知功能损害与病情的严重程度有关,认知功能的降低可能提示病人额叶功能的缺损.     

Methadone doses upon multiple readmissions to inpatient detoxification: Clinical evidence for very moderate opioid tolerance

Escalation of drug use by addicts has traditionally been interpreted as tolerance to the drug's effects. On the basis of animal behavioral data, several groups have recently proposed alternative explanations, i.e., that such an escalation of drug dose might not be based on tolerance but rather be indicative of (i) sensitization to the reinforcing effect or the incentive salience of the drug of abuse or (ii) shifts in baseline mood, i.e., allostasis. In the present study, the emergence of opioid tolerance or sensitization during the progression of opioid dependence was assessed by comparing the methadone doses that were initially required to alleviate the opioid withdrawal symptoms of intravenous opioid users who presented for detoxification upon 3-7 consecutive admissions over the course of up to 84 months. Upon the second admission, the 48 surveyed male patients needed 115 +/- 6% (p = 0.012) and the 32 female patients needed 121 +/- 12% (p = 0.01) of the methadone dose required upon the first admission. Upon the third admission, the respective values were 121 +/- 8% (males; p = 0.013) and 111 +/- 12% (females; n.s.), and upon the fourth admission, 125 +/- 14% (males; p = 0.026) and 131 +/- 14 (females; p = 0.01). Inter-admission intervals averaged 14 +/- 1 months (n = 135) for males and 13 +/- 1 months (n = 91) for females and were not significantly different across consecutive admissions, suggesting that tolerance did not develop faster upon repetition of abuse-withdrawal cycles. In conclusion, the intravenous opioid users surveyed in the present study developed only very moderate tolerance during the repeated abuse-detoxification cycles that were typical for their disease progression. The present data do not support the notion that sensitization to the opioids' reinforcing effects occurred in this naturalistic clinical sample.     

Effects of buprenorphine and methadone in methadone-maintained subjects

Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study characterized the agonist and antagonist effects of acute doses of buprenorphine and methadone in subjects maintained on either 30 (n=7) or 60 (n=6) mg/day oral methadone. Test doses of placebo [sl. and PO), methadone (15, 30, and 60 mg PO) and buprenorphine (2, 4, and 8 mg sl.) were administered to volunteers residing on a closed residential unit. Subjective, physiological, observer-rated, and cognitive/psychomotor measures were collected for 6.5 h after test doses. Test doses of methadone, but not buprenorphine, constricted pupils and produced dose-related increases on subjective report measures reflecting opioid agonist drug effects. Agonist effects of methadone were more prominent in the 30 mg than in the 60 mg methadone maintenance condition. Buprenorphine, but not methadone, precipitated opioid withdrawal signs and symptoms that were more prominent in the 60 mg than in the 30 mg methadone maintenance condition. These findings suggest that abrupt transition from methadone to buprenorphine may produce patient discomfort that is positively related to both methadone maintenance dose and buprenorphine transition dose.     

Cost analysis of clinic and office-based treatment of opioid dependence: results with methadone and buprenorphine in clinically stable patients

The cost of providing and receiving treatment for opioid dependence can determine its adoption. To compare the cost of clinic-based methadone (MC, n=23), office-based methadone (MO, n=21), and office-based buprenorphine (BO, n=34) we performed an analysis of treatment and patient costs over 6 months of maintenance in patients who had previously been stabilized for at least 1 year. We performed statistical comparisons using ANOVA and chi-square tests and performed a sensitivity analysis varying cost estimates and intensity of clinical contact. The cost of providing 1 month of treatment per patient was $147 (MC), $220 (MO) and $336 (BO) (p<0.001). Mean monthly medication cost was $93 (MC), $86 (MO) and $257 (BO) (p<0.001). The cost to patients was $92 (MC), $63 (MO) and $38 (BO) (p=0.102). Sensitivity analyses, varying cost estimates and clinical contact, result in total monthly costs of $117 to $183 (MC), $149 to $279 (MO), $292 to $499 (BO). Monthly patient costs were $84 to $133 (MC), $55 to $105 (MO) and $34 to $65 (BO). We conclude that providing clinic-based methadone is least expensive. The price of buprenorphine accounts for a major portion of the difference in costs. For patients, office-based treatment may be less expensive.     

Evaluation of levo-alpha-acetylmethdol (LAAM) as an alternative treatment for methadone maintenance patients who regularly experience withdrawal: a pharmacokinetic and pharmacodynamic analysis

The aim of this study was to determine if substitution of daily methadone with second daily levo-alpha-acetylmethadol (LAAM) would convert non-holders on methadone into holders on LAAM, and to compare plasma concentration-time profiles of (R)-methadone with LAAM and its two metabolites. Sixteen stable methadone maintenance treatment participants (non-holders, n = 8) were randomly allocated to continue methadone for 3 months or switch to LAAM for 3 months, and then crossed over to the alternative drug for 3 months. At steady state, there were two testing sessions (24 h for methadone and 48 h for LAAM), during which opioid withdrawal severity, respiration rate and pupil diameter were measured 10-11 times and venous blood was collected 13-15 times. Ten age- and gender-matched controls underwent one 48-h test session. Areas under the withdrawal severity score versus time curve (AUC(0-47) hours for LAAM and controls; AUC(0-24) x 2 for methadone) were similar in holders on methadone and LAAM (P = 0.62), but were greater in non-holders when they were taking methadone than LAAM (P < 0.001). Respiratory depression and pupillary constriction were similar for LAAM and methadone. In comparison to (R)-methadone, plasma nor- and dinor-LAAM concentrations fluctuated little over the dosing interval. LAAM converted methadone non-holders into LAAM holders. LAAM may therefore be useful in selected MMT non-holders and improve retention in opioid treatment programs.     

Prefrontal grey-matter changes in short-term and long-term abstinent methamphetamine abusers

Authors explored grey-matter density in 29 methamphetamine abusers and 20 healthy comparison subjects using voxel-based morphometry. Grey-matter density changes and performances on the Wisconsin Card Sorting test (WCST) were also compared between 11 short-term (<6 months) and 18 long-term (>or=6 months) abstinent methamphetamine abusers. Methamphetamine abusers had lower grey-matter density in the right middle frontal cortex (corrected p<0.05) and more total errors in the WCST (p<0.01) relative to healthy comparison subjects. Grey-matter density decrease in the right middle frontal cortex correlated with total errors in the WCST in methamphetamine abusers (r=-0.45). Long-term abstinent abusers had significantly less right middle frontal grey-matter density decrease (p<0.01) and total errors in the WCST (p<0.01) than short-term abstinent abusers, but more than the healthy comparison subjects. We report that methamphetamine abusers have prefrontal grey-matter deficit, which may, in part, recover with long-term abstinence.     

Availability of Reliable Serum Methadone Determination for Management of Symptomatic Patients

Methadone, when used in the appropriate dose, prevents opioid withdrawal during the 24-hour period following medication. However, the appropriate dose for a given patient may be difficult to determine due to variations in methadone metabolism which is affected by many factors. Early opioid withdrawal, requiring a higher dose of methadone, is often difficult to diagnose because many of the symptoms are also symptoms of other syndromes common in the methadone maintenance population. In this study, ten patients in stable methadone maintenance treatment reporting ≥ 4 Himmelsbach signs of abstinence were compared with ten patients reporting fewer symptoms. Until recently, accurate, precise, and affordable determination of serum methadoe level has not been readily available from commercial laboratories. This study has found that such measures are now available. Serum specimens from each subject were sent to three commercial laboratories for determination of serum methadone level. Results from the three laboratories were highly correlated. No statistical correlation was found between serum methadone level and number of Himmelsbach signs. Of the subjects reporting four or more symptoms, 40% had low serum methadone levels (< 150 ng/ml); 60% did not. Of the subjects reporting fewer than four symptoms, 90% had serum methadone levels ≥ 150 ng/ml. Subjects with ≥ 4 Himmelsbach signs had lower dose-adjusted serum methadone levels, the amount of methadone circulating per mg dose, (t = 1.54, p = .0702). Thus, for patients who report symptoms which could be attributable to opioid withdrawal, measurement of serum methadone level may help to differentiate complaints due to early abstinence from those due to other medical conditions.