Opioid treatment for opioid withdrawal in newborn infants.

BACKGROUND: Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems. OBJECTIVES: To assess the effectiveness and safety of using an opioid for treatment of NAS due to withdrawal from opioids in newborn infants. SEARCH METHODS: We ran an updated search on 17 September 2020 in CENTRAL via Cochrane Register of Studies Web and MEDLINE via Ovid. We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for eligible trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi- and cluster-RCTs which enrolled infants born to mothers with opioid dependence and who were experiencing NAS requiring treatment with an opioid. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 16 trials (1110 infants) with NAS secondary to maternal opioid use in pregnancy. Seven studies at low risk of bias were included in sensitivity analysis. Opioid versus no treatment / usual care: a single trial (80 infants) of morphine and supportive care versus supportive care alone reported no difference in treatment failure (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.41 to 4.07; very low certainty evidence). No infant had a seizure. The trial did not report mortality, neurodevelopmental disability and adverse events. Morphine increased days hospitalisation (mean difference (MD) 15.00, 95% CI 8.86 to 21.14; very low certainty evidence) and treatment (MD 12.50, 95% CI 7.52 to 17.48; very low certainty evidence), but decreased days to regain birthweight (MD -2.80, 95% CI -5.33 to -0.27) and duration (minutes) of supportive care each day (MD -197.20, 95% CI -274.15 to -120.25). Morphine versus methadone: there was no difference in treatment failure (RR 1.59, 95% CI 0.95 to 2.67; 2 studies, 147 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study reported no difference in days hospitalisation (MD 1.40, 95% CI -3.08 to 5.88; 116 infants; low certainty evidence), whereas data from two studies found an increase in days treatment (MD 2.71, 95% CI 0.22 to 5.21; 147 infants; low certainty) for infants treated with morphine. A single study reported no difference in breastfeeding, adverse events, or out of home placement. Morphine versus sublingual buprenorphine: there was no difference in treatment failure (RR 0.79, 95% CI 0.36 to 1.74; 3 studies, 113 infants; very low certainty evidence). Neonatal or infant mortality and neurodevelopmental disability were not reported. There was moderate certainty evidence of an increase in days hospitalisation (MD 11.45, 95% CI 5.89 to 17.01; 3 studies, 113 infants), and days treatment (MD 12.79, 95% CI 7.57 to 18.00; 3 studies, 112 infants) for infants treated with morphine. A single adverse event (seizure) was reported in infants exposed to buprenorphine. Morphine versus diluted tincture of opium (DTO): a single study (33 infants) reported no difference in days hospitalisation, days treatment or weight gain (low certainty evidence). Opioid versus clonidine: a single study (31 infants) reported no infant with treatment failure in either group. This study did not report seizures, neonatal or infant mortality and neurodevelopmental disability. There was low certainty evidence for no difference in days hospitalisation or days treatment. This study did not report adverse events. Opioid versus diazepam: there was a reduction in treatment failure from use of an opioid (RR 0.43, 95% CI 0.23 to 0.80; 2 studies, 86 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study of 34 infants comparing methadone versus diazepam reported no difference in days hospitalisation or days treatment (very low certainty evidence). Adverse events were not reported. Opioid versus phenobarbital: there was a reduction in treatment failure from use of an opioid (RR 0.51, 95% CI 0.35 to 0.74; 6 studies, 458 infants; moderate certainty evidence). Subgroup analysis found a reduction in treatment failure in trials titrating morphine to ≧ 0.5 mg/kg/day (RR 0.21, 95% CI 0.10 to 0.45; 3 studies, 230 infants), whereas a single study using morphine < 0.5 mg/kg/day reported no difference compared to use of phenobarbital (subgroup difference P = 0.05). Neonatal or infant mortality and neurodevelopmental disability were not reported. A single study (111 infants) of paregoric versus phenobarbital reported seven infants with seizures in the phenobarbital group, whereas no seizures were reported in two studies (170 infants) comparing morphine to phenobarbital. There was no difference in days hospitalisation or days treatment. A single study (96 infants) reported no adverse events in either group. Opioid versus chlorpromazine: there was a reduction in treatment failure from use of morphine versus chlorpromazine (RR 0.08, 95% CI 0.01 to 0.62; 1 study, 90 infants; moderate certainty evidence). No seizures were reported in either group. There was low certainty evidence for no difference in days treatment. This trial reported no adverse events in either group. None of the included studies reported time to control of NAS. Data for duration and severity of NAS were limited, and we were unable to use these data in quantitative synthesis. AUTHORS' CONCLUSIONS: Compared to supportive care alone, the addition of an opioid may increase duration of hospitalisation and treatment, but may reduce days to regain birthweight and the duration of supportive care each day. Use of an opioid may reduce treatment failure compared to phenobarbital, diazepam or chlorpromazine. Use of an opioid may have little or no effect on duration of hospitalisation or treatment compared to use of phenobarbital, diazepam or chlorpromazine. The type of opioid used may have little or no effect on the treatment failure rate. Use of buprenorphine probably reduces duration of hospitalisation and treatment compared to morphine, but there are no data for time to control NAS with buprenorphine, and insufficient evidence to determine safety. There is insufficient evidence to determine the effectiveness and safety of clonidine.

Pharmacological therapies for management of opium withdrawal.

BACKGROUND: Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. OBJECTIVES: To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. SEARCH METHODS: We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. SELECTION CRITERIA: Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low-quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low-quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low-quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low-quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low-quality evidence).Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) -3.56, 95% CI -5.97 to -1.15; 1 study, 60 participants, very low-quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD -1.40, 95% CI -2.93 to 0.13; 1 study, 34 participants, very low-quality evidence), and results in favour of buprenorpine when rated by participants (MD -11.80, 95% CI -15.56 to -8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI -2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD -2.20, 95% CI -6.72 to 2.32; 1 study, 40 participants).Comparing clonidine versus buprenorphine in an outpatient setting, more adverse effects were reported in the clonidine group (1 study, 76 participants). Higher numbers of participants in the clonidine group experienced hypotension at days 5 to 8, headache at days 1 to 8, sedation at days 5 to 8, dizziness and dry mouth at days 1 to 10, and nausea at days 1 to 9. Sweating was reported in a significantly higher number of participants in the buprenorphine group at days 1 to 10. We found no difference between groups for all the other comparisons considering this outcome.Comparing different dosages of the same pharmacological detoxification treatment, a high dose of clonidine (1 to 1.2 mg/day) did not differ from a low dose of clonidine (0.5 to 0.6 mg/day) in completion of treatment in an inpatient setting (RR 1.00, 95% CI 0.84 to 1.19; 1 study, 68 participants), however a higher number of participants with hypotension was reported in the high-dose group (RR 3.25, 95% CI 1.77 to 5.98). Gradual reduction of methadone was associated with more adverse effects than abrupt withdrawal of methadone (RR 2.25, 95% CI 1.02 to 4.94; 1 study, 20 participants, very low-quality evidence). AUTHORS' CONCLUSIONS: Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low-quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.

Quality of life of patients treated with opium tincture or methadone: A randomized controlled trial.

OBJECTIVE: Quality of life (QoL) is an increasingly recognized patient-centered treatment outcome in individuals with opioid use disorder. There is a gap in literature on the impact of opium tincture (OT) on patients' QoL compared to standard treatment options such as methadone. This study aimed to compare the QoL of participants with opioid use disorder receiving OAT using OT or methadone and identify the factors associated with their QoL during treatment. METHODS: The opium trial was a multicenter non-inferiority randomized clinical trial in four private OAT outpatient clinics in Iran. The study assigned patients to either OT (10 mg/ml) or methadone sirup (5 mg/ml) for a follow-up of 85 days. QoL was assessed using the brief version of the World Health Organization Quality of Life instrument (WHOQOL- BREF). RESULTS: A total of 83 participants, 35 (42.2%) in the OT arm and 48 (57.8%) in the methadone arm, completed the WHOQOL-BREF in full and were included in the primary analysis. The mean score of patients' QoL showed improvement compared to baseline, but differences were not statistically significant between OT and methadone arms (p = 0.786). Improvements were mainly observed within the first 30 days of receiving treatment. Being married and lower psychological distress were associated with an improved QoL. Within the social relationships domain, male gender showed significantly higher QoL compared to females. CONCLUSION: OT shows promise as an OAT medication, comparable to methadone in improving patients' QoL. There is a need to incorporate psychosocial interventions to further sustain and improve the QoL in this population. Identifying other social determinants of health which affect QoL and the cultural adaptation of assessments for individuals from various ethnocultural backgrounds are critical areas of inquiry.

Opium tincture versus methadone for opioid agonist treatment: a randomized controlled trial.

AIM: To test if opium tincture (OT) was non-inferior to methadone in retaining participants in opioid agonist treatment (OAT). DESIGN: A Phase III, multi-centre, parallel-group, non-inferiority, double-blind randomized controlled trial with an allocation ratio of 1:1. Participants were provided treatment and followed for a period of 85 days. SETTING: Four OAT clinics in Iran. PARTICIPANTS: Two hundred and four participants with opioid use disorder [mean age (standard deviation) = 37.4 (9.3); female 11.3%] recruited between July 2017 and January 2018. INTERVENTIONS: Participants were assigned to either OT (102) or methadone (102) using a patient-centred flexible dosing strategy. MEASUREMENTS: Treatment retention over 85 days was the primary outcome. Self-reported opioid use outside treatment and occurrence of adverse events (AEs) were the secondary outcomes. FINDINGS: Remaining in treatment at the end of the follow-up were 68.6% in the methadone arm and 59.8% in the OT arm. The relative retention rate of methadone to OT was 1.15 (0.97, 1.36) in both intent-to-treat and per-protocol analyses; non-inferiority was not supported statistically, as the upper bound of the confidence interval exceeded our pre-specified non-inferiority margin (1.25). Opioid use outside treatment was reported by 30.3% of OT (n = 152) and 49.4% of methadone (n = 168) patients, a difference in proportions of -19%: 90% confidence interval (-28%, -10%). The total count of AEs in the OT arm (22 among nine individuals) was significantly higher (P = 0.04) than that in the methadone arm (three among two individuals). Nausea was the most common side effect. CONCLUSION: While this study could not conclude the non-inferiority of opium tincture (OT) to methadone for retaining patients in opioid agonist treatment, OT retained 60% of participants to end of follow-up (85 days) and was superior to methadone in reducing self-reported opioid use outside treatment.

A study on methylation of two CpG islands of MAOA gene promoter among opium-addicted males undergoing methadone treatment.

The association between methylation of MAOA gene promoter and alcohol and nicotine dependence has been demonstrated in women but not in men yet. Antisocial personality disorder (ASPD) and substance use disorders (SUD) are two types of disorders that could highly be influenced by methylation-induced changes in MAOA function. The aim of the current study is to investigate the effect of opioid addiction on methylation of MAOA gene promoter in males. DNA was extracted from the whole blood of all samples (29 opium-addicted individuals undergoing methadone treatment and 28 healthy people) according to the extraction protocol, followed by treating these samples with bisulfite kits. The investigated region including two CpG islands in the promoter region of MAOA gene contained 35 CpG dinucleotides investigated through Sanger sequencing method. The frequency of methylation at two CpG islands of MAOA gene promoter regions was equal to zero among addicted individuals undergoing methadone treatment and healthy peoples. Then, comparing methylation levels among the study group is not applicable. In conclusion, there was no association between opium addiction and methylation of the MAOA promoter regions in opium-addicted male undergoing methadone treatment.

Factors influencing engagement and utilisation of opium tincture-assisted treatment for opioid use disorder: A qualitative study in Tehran, Iran.

INTRODUCTION: In response to a high burden of opioid use disorder (OUD), Iran established a network of opioid agonist treatment (OAT) centres beginning in 2002. To increase treatment diversity, particularly for patients who use opium as their drug of choice, opium tincture (OT)-assisted treatment was introduced to the network. This study aimed to explore factors influencing OT-assisted treatment selection for OUD in Tehran, Iran. METHODS: We conducted 54 in-depth interviews with patients with OUD (n = 33), family members of patients (n = 9) and drug treatment providers (n = 12). Participants were recruited from 12 drug treatment centres across Tehran, between September and November 2019. All interviews were audio-recorded, transcribed and coded in OpenCode 4.02 software and analysed using thematic analysis. RESULTS: Study participants more commonly reported individual-level factors as facilitators (e.g. to reduce harms associated with illicit opioid use, achieve recovery through a gradual dose reduction regimen combined with Congress 60 recovery program) and structural level factors (e.g. low adoption by OAT system and lack of familiarity of treatment providers) as barriers for utilisation of OT-assisted treatment regimens. OT was perceived to produce lower levels of physiological dependence than methadone, but the requirement for twice supervised dosing was restrictive. Low familial and community acceptance were also seen as barriers to access. DISCUSSION AND CONCLUSIONS: This research identified a range of perceived benefits for OT-assisted treatment ranging from harm reduction to an intermediate step to achieve recovery. However, several structural-, individual-, familial- and community-level barriers impede its availability and acceptability.

Substance of choice, impact of heroin or opium on treatment retention in a multicentre randomised controlled trial in Iran.

INTRODUCTION: In the Middle East and Asia, illicit opioid use exists across a spectrum between heroin and opium. The impact of primary opioid of choice on opioid agonist treatment retention has not been well evaluated previously, especially for opium tincture, an increasingly popular form of opioid agonist treatment in Iran. This study investigates the relationship between primary opioid of choice, namely heroin or opium, and retention in opium tincture and methadone treatment. METHODS: Participants with opioid use disorder (n = 204) were randomised to receive opium tincture or methadone. All participants were categorised as mainly using opium or heroin. Bivariate analyses between treatment retention and primary opioid of choice (P < 0.05) and logistic regression were conducted. RESULTS: Among the 191 participants included in this analysis, heroin was the primary substance of choice for 135 participants (70.7%) and opium for 56 (29.3%). Bivariate analysis showed that the opium group was more likely to be satisfied with family situation, employed and retained in treatment than the heroin group while less likely to experience incarceration and use multiple substances. When adjusting for covariates, primary opioid of choice was not significantly associated with retention in either methadone or opium tincture treatment arm. DISCUSSION AND CONCLUSIONS: Positive factors, such as employment, housing and family support, seem to collectively explain the higher retention in treatment among those who primarily use opium compared to those who use heroin. To optimise retention in opioid agonist treatment, biopsychosocial care models should be further evaluated to improve psychosocial functioning.

Opium tincture-assisted treatment for opioid use disorder: A systematic review.

BACKGROUND: Some countries have used opioid agonist medications other than methadone and buprenorphine as a strategy to increase treatment diversity. In Iran and other countries where opium use is common and culturally tolerated, opium tincture (OT) has gained growing popularity and been approved to treat opioid use disorder (OUD). Given the increasing interest in this intervention, we conducted a systematic review of the literature to evaluate the safety and efficacy of OT-assisted treatment for OUD. METHODS: We systematically searched international (MEDLINE, Embase, CINAHL, PsychInfo, Google Scholar, and clinicaltrials.gov) and Iranian (Scientific Information Database (SID), Iranmedex, IranDoc, digital library of Iran's Drug Control Headquarters and the Iranian Registry for Clinical Trials) databases on November 04, 2020 without any language or publication date limitations. Two reviewers screened the titles, abstracts, and full-text of the retrieved records to find clinical trials or observational studies that assessed the safety and efficacy of OT-assisted treatment for OUD. RESULTS: We screened 1301 records and included 21 unique studies on assisted withdrawal (n = 5), maintenance (n = 9), and gradual dose reduction (n = 7) treatment regimens. Most studies included men and people with opium use disorder. We found only six randomized controlled trials (RCT). Our results showed that OT-assisted treatment is associated with comparable outcomes with methadone treatment in both assisted withdrawal and maintenance treatment regimens. We also found promising results for using gradual dose reduction regimen of OT-assisted treatment from observational studies. The overall quality of scientific evidence was low due to the limited number RCT and high risk of bias in the included studies. CONCLUSIONS: The body of evidence supporting the safety and efficacy of OT-assisted treatment in assisted withdrawal, maintenance, and gradual dose reduction regimens is limited but somewhat promising, in particular among people with opium use disorder. Our review calls for higher-quality studies to investigate the comparative efficacy of these treatment methods with standard pharmacotherapies for OUD.

Effects of methadone, opium tincture and buprenorphine maintenance therapies on thyroid function in patients with OUD.

Various types of medications are used as maintenance therapies for substance use disorder; However, the side effects of these drugs are shown to restrict their use and increase the risk of relapse in patients. As a result, alternative maintenance therapies are tested in the hope for optimum therapy. Since opium tincture is a new and innovative maintenance treatment in Iran, we attempted to compare the therapeutic and side effects of opium tincture with two standard therapies, i.e., methadone and buprenorphine. Hence, thyroid function was tested in three methods of maintenance therapies with methadone, buprenorphine, and opium tincture in a cross-sectional study. In this study, 150 patients with the mean age of 51.63 ± 13.56 years and a history of opioid or opioid-derivatives use disorder, underwent the maintenance treatment with methadone, buprenorphine, and opium tincture at Bojnurd Addiction Treatment Centers in northeastern Iran. These patients were selected using convenience sampling. Then, they were placed into three treatment groups of methadone, buprenorphine, and opium tincture. The thyroid functionality was assessed with measuring TSH, fT4, fT3, T3RU, and Anti TPO, carried out in a reference laboratory. Finally, these data were analyzed by ANOVA using SPSS.16 software. The results showed that there was no significant difference in the average levels of TSH, fT3, fT4, and Anti TPO in these treatment groups; except for T3RU concentration, which was increased significantly in the opium tincture group as compared to the methadone treated group. Also, the frequency of fT4, and T3RU disorders demonstrated a significant change in three groups. The findings of the present study demonstrated that opium tincture in comparison with methadone could increase T3RU levels resulting in euthyroidism possibly through TBG.

Opioid Crisis Along Mexico's Northern Border: Treatment Needs Mexican Opioid Crisis.

BACKGROUND: Heroin production for external markets and low rates of use in Mexico have had a long history. A recent shift toward an increase in use and related problems calls for the evaluation of treatment needs in order to draw recommendations for policies. METHODS: The objectives were to identify predictors of choice of treatment and barriers to care among persons that had been with no treatment. The study included a convenience sample of 600 face-to-face interviews of people 18 years of age and older and a rapid HIV and HCV tests in three cities on Mexico's Northern Border: Ciudad Juárez, San Luis Río Colorado and Tijuana. The choice of treatment (methadone, other pubic or private treatments with no experience with methadone maintenance and only self-help or religious care), was analyzed though a multiple logistic multimodal regression analysis. Informed consents to be interviewed and for HIC and HIV were signed by interviewers. RESULTS: The majority of persons interviewed were males (89.7%) with an average age of 40. Having emigrated to the United States and a greater length of heroin use predicted seeking methadone treatment versus public or private treatment or informal care. The most important barriers to care were lack of information and stigma. HIC, HIV and other infectious and chronic diseases including depression were often unattended. CONCLUSIONS: There is a need to reform treatment policies in order to cover this w emerging and demanding problem.

Comparing opium tincture and methadone for medication-assisted treatment of patients with opioid use disorder: Protocol for a multicenter parallel group noninferiority double-blind randomized controlled trial.

OBJECTIVES: This is the first study to compare the safety and efficacy of opium tincture (OT) with methadone for treatment of opioid use disorder. METHODS: In this multicenter, double-blind, noninferiority controlled trial, a stratified sample of 204 participants with opioid use disorder were recruited from community outreach, drop-in centers, and triangular clinics. Participants were excluded in case of active participation in another treatment program for opioid use disorder, hypersensitivity to trial medications, pregnancy, and certain serious medical conditions. They were randomized to receive either OT or methadone with an allocation ratio of 1:1 using a patient-centered flexible dosing strategy. Eligible participants were followed for a period of 12 weeks. Primary outcome is the difference in percentage of patients retained in the treatment. Secondary outcomes are craving, withdrawal symptoms, physical health, mental health, quality of life, and severity of substance use problems, cognitive function, safety profile, cost-effectiveness, and participants' satisfaction. Both intention-to-treat and per-protocol analyses will be conducted. The Ethics Board of the University of British Columbia and Tehran University of Medical Sciences approved the study. (clinicaltrials.gov; NCT02502175). RESULTS: To be reported after final analysis. CONCLUSIONS: If shown to be effective, OT will diversify the options for medication-assisted treatment of opioid use disorder.

A chart review comparing paregoric to methadone in the treatment of neonatal opioid withdrawal.

Neonatal opioid withdrawal often requires treatment but there have been few recent studies of current pharmacological interventions to guide treatment. This retrospective chart review provides an exploratory examination of newborns treated with either methadone or paregoric for opioid withdrawal and outlines dosage ranges and intervals, side effects, and clinical outcomes of the two regimens. The outcome variables examined were time to resolution of withdrawal symptoms, rate of decrease in symptom severity, and length of hospital stay. There were no observed differences in outcome variables between the two treatment groups and side effect profiles were similar. Dosages, dosage intervals, and tapering regimens were consistent with American Academy of Pediatrics recommendations. Although the sample size is small and standardized regimens were not used, this study provides preliminary data about dosing levels and dosing intervals of these two pharmacologic treatment agents. Both groups of infants had favorable outcomes, although given the variation in treatment regimens it is difficult to draw an equation of equivalency. These results are applicable to the design of future studies of pharmacological interventions.

Changes in estradiol and cortisol production rates in men under the influence of narcotics.

The production rates of estradiol and cortisol in two male opiate addicts while on narcotic maintenance, were in the low normal or subnormal range. There was a sharp several-fold increase upon withdrawal with a subsequent fall to normal values after a period of abstinence. The changes in estradiol production rates were proportionally greater than those of cortisol and suggest that they were due to changes in testicular secretion of the precursor testosterone.

Opiate addiction and suicidal behaviors.

The authors tested the hypothesis that people addicted to opiates manifest more psychopathology in areas that have been identified as predictors for high risk of suicidal behavior than do normal control subjects. They gave 278 patients in a methadone maintenance program and 207 normal control subjects the index of Potential Suicide (IPS), a scale designed to assess suicidal risk. Using discriminate function analysis, the authors found that 87% of 100 of the methadone patients and 98% of 100 of the normal control subjects were correctly identified on the basis of the IPS data.

Experiences of a methadone detoxification programme for opium addicts.

The conduction of a new programme of methadone detoxification of opium addicts in a general hospital setting is described. A blind technique of dispensing methadone in a powdered form mixed with powdered aspirin to two groups of opium addicts was used: Group A were given a gradual reduction of the methadone over a period of ten days, while group B were maintained on the initial stabilising dose for the ten days and then abruptly withdrawn from methadone on the eleventh day. It was observed that the number of complaints and abstinence symptoms was markedly reduced in Group B. It is suggested that this technique is a major improvement over the standard progressive reduction method of methadone detoxification. A follow-up of these patients over a period of 1 1/2 years is reported.

The safety and value of naloxone as a therapeutic aid.

The safety and value of naloxone as a therapeutic aid was demonstrated in a large population of narcotic dependent persons over a two-year period. Naloxone was used to precipitate the narcotic withdrawal syndrome. This withdrawal syndrome was rated according to a previously developed scale. Retrospectively, naloxone rating scores were correlated with the patients' initial dose of methadone. With patients who received 0.8 mg naloxone, good correlation was obtained between the naloxone test score and the optimum methadone dose (mg), as indicated by the patients' physical status during the initial three days of methadone treatment. Three hundred and sixty-three tests were administered to 343 persons and no individuals developed any serious effects such as convulsions, syncope or cardiovascular collapse.

Onset and pattern of substance use in intravenous drug users of an opiate maintenance program.

OBJECTIVES: To assess the initiation of substance use of participants in an opiate maintenance program by a cross-sectional survey. METHOD: Participants (n=184) filled out a questionnaire assessing age at initial substance use and age at onset of regular drug use. RESULTS: Of 15 substances investigated, alcohol, nicotine, analgesics and marijuana were initiated and consumed regularly before the age of 18 years. Barbiturates, benzodiazepines, cocaine, and opiates were begun later. The time gap between initial and regular use varied depending on the substance. Regular use exceeded 50% for alcohol, benzodiazepines, cocaine, heroin, marijuana and nicotine. CONCLUSIONS: Specific knowledge about the age of onset and sequence of substances used by drug addicts may help to prevent substance use more age specifically.

Pupillometric changes during gradual opiate detoxification correlate with changes in symptoms of opiate withdrawal as measured by the Weak Opiate Withdrawal Scale.

The relationship between pupil size and subjective symptoms of opiate withdrawal during gradual opiate agonist detoxification has not yet been studied. In the current study, the authors sought to determine the relationship between pupil size and intensity of opiate withdrawal symptoms. To accomplish this, they examined 19 subjects meeting DSM-IV criteria for opiate dependence (304.00) on agonist therapy. All subjects were undergoing opiate detoxification with either methadone or the longer-acting 1-alpha acetylmethadol (LAMM). During two separate visits, subjects' pupil sizes were assessed in the dark using a pupillometer. At each visit, subjects completed two standardized assessment tools (the Subjective Opiate Withdrawal Scale [SOWS] and the Weak Opiate Withdrawal Scale [WOWS]) for measuring subjective symptoms of opiate withdrawal. It was found that changes in pupil size significantly correlated with WOWS, but not with SOWS, scores. Larger pupil sizes were associated with less withdrawal distress. The sensitivity of the pupillometric test to detect increases in opiate craving during opiate agonist medication reduction was 92%, with a specificity of 57%. The predictive value of a positive test was 79%, whereas the predictive value of a negative test was 80%. Pupillometry may provide an objective measure of the intensity of opiate withdrawal in subjects during gradual methadone detoxification.

Survey of methadone patients in Canada.

We present the results of a survey outlining the frequency of certain activities associated with drug-seeking behaviour, e.g. needle sharing, illicit activity. The data presented are based upon information concerning 1,000 patients receiving long-term Methadone as a treatment for opioid dependence. These data are unique in that specific information of this nature has never before been made available in Canada, and are of interest in view of the AIDS epidemic.

Hepatitis C in methadone maintenance patients: prevalence and public policy implications.

OBJECTIVE: This study measured the extent and examined implications of hepatitis C (HCV) infection in a methadone maintenance treatment (MMT) population. METHOD: Four hundred and sixty patients were tested for HCV-Ab, hepatic enzymes and bilirubin, HCV-RNA, and hepatitis B antibody. RESULTS: Overall, 87% of this population had evidence of HCV-Ab. Among drug injectors (IDU), 96% were HCV-Ab positive. Among a subset of Laotian opium-smoking patients prevalence was only 11%. Sixty-two percent of patients with HCV-Ab had detectable HCV-RNA. Only 41% had elevated hepatic enzymes, and 5% had elevated bilirubin levels. All age groups were equally infected. Systemic problems in screening and treating HCV in drug users were identified. CONCLUSION: HCV infection poses significant long-term health risks for this population. Harm reduction interventions aimed at reducing transmission of HCV and other needle-related infectious disease deserves more consideration.