Drug-induced prolonged corrected QT interval in patients with methadone and opium overdose.

BACKGROUND: Iran is a country with the highest rate of opioid addiction in the world. The most commonly used opioid in Iran is opium, and methadone is in second place. The trend of drug use has changed from opium to methadone from 2006 to 2011. Presence of a large number of addicted people and methadone maintenance therapy clinics make methadone readily available in Iran. Therefore, evaluation of the epidemiological characteristic of methadone toxicity and its effects on the heart is essential. METHODS: In This cross-sectional, retrospective, descriptive, analytical study all patients with methadone or opium toxicity who had been admitted to Vasei hospital, Sabzevar, Iran, during the years 2015 and 2016 were included, and their records were evaluated. Demographic data, addiction history, underlying diseases, and the outcome of admission were recorded. Then, corrected QT interval (QTc) of the first ECG of the patients after admission was evaluated. RESULTS: The Majority of toxicities occurred in those above 30 years of age (71.4%), who lived in cities (62.8%), and were married (69.2%). A positive history of addiction was considerably higher in the opium group (72.3% versus 43.3%). There was no significant difference regarding QTc prolongation between patients with methadone and opium toxicity (p = 0.3). CONCLUSION: QTc prolongation is one of the adverse effects of methadone or opium overdose. It seems that significant QTc prolongation is not uncommon among patients with opium overdose.

Therapy of the neonatal abstinence syndrome with tincture of opium or morphine drops.

BACKGROUND: Treating opioid-addicted women with methadone in pregnancy increased the number of newborns suffering from neonatal abstinence syndrome (NAS). High-pitch crying, insomnia, tremor, myoclonic jerks, vomiting, diarrhoea and poor weight gain were reported symptoms, which were evaluated using the Finnegan (F)-score. Earlier phenobarbital or paregoric had been used to suppress symptoms. We surveyed the administration of pure mu-agonist morphine (MO) in comparison to the alcoholic opioid mixture in tincture of opium (TO). Thirty-three newborns were included in the survey, after informed consent by their parents. RESULTS: NAS started 3-5 days after delivery and lasted for 27 or 30 days (mean) in the TO and MO groups, respectively. In either of the tested parameters, we found no significant differences between the two groups (2P < 0.05). The maximum F-score was similar in both groups, but the dose to suppress NAS was higher in the MO group (0.6-0.5 mg/day; total dose 61.6-42.7 mg of morphine). The duration of the therapy was longer in the MO than in the TO group (37.5-32.4 days). On the other hand the weight gain was better in the MO group than in the TO group (25-19 g/day), but was reduced in both groups compared with healthy newborns. CONCLUSIONS: Morphine is suitable to treat NAS in a similar manner as tincture of opium, but avoids unwanted effects of the alcoholic extracts with various alkaloids in the tincture of opium and allows better weight gain of the newborns.

Neurobehavioral effects of treatment for opiate withdrawal.

A partially randomised, controlled trial was performed to test the hypothesis that opiate exposed infants treated with diluted tincture of opium (DTO) and phenobarbital would have better neurobehavioral scores than infants treated with DTO alone. Compared with those treated with DTO alone (n = 15), infants treated with DTO and phenobarbital (n = 17) were more interactive, had smoother movements, were easier to handle, and less stressed. Dual treatment results in improved neurobehavioral organisation during the first three weeks of life, which may indicate a more rapid recovery from opiate withdrawal.

Clinical effects of parenteral narcotics in hospitalized medical patients.

Of 38,221 hospitalized medical patients monitored by a drug surveillance program, 1821 (4.8 per cent) received morphine, 504 (1.3 per cent) received codeine, 493 (1.3 per cent) received papaveretum, 115 (0.3 per cent) received hydromorphone, and 101 (0.3 per cent) received methadone parenterally. Hydromorphone had an unusually high adverse reaction rate (18 per cent); therefore, it probably should not be used since other equally effective strong analgesics are available. Adverse reactions occurred in 2 per cent of papaveretum recipients, in 4 per cent of methadone and codeine recipients, and in 6 per cent of morphine recipients. Gastrointestinal reactions (primarily nausea, vomiting, and constipation) were most common. Central nervous system disturbances (primarily respiratory depression, drowsiness, and confusion) were second most common. Adverse reactions occurred more often with higher doses of morphine and codeine; the dose-response relationship could not be evaluated for the other three drugs. Life-threatening adverse reactions were reported in 28 patients. Respiratory depression was the most common life-threatening reaction. Most patients with these reactions were seriously ill, and many received other drugs that may have contributed to the event.

Diazepam abuse in pregnant women on methadone maintenance. Implications for the neonate.

The authors found that the course and treatment of narcotic withdrawal in two neonates was complicated by prenatal exposure to high doses of diazepam, or Valium (Roche Laboratories, Nutley, NJ). Both of the mothers were on methadone maintenance for narcotic dependency prior to the diagnosis of pregnancy. The authors documented maternal intake of diazepam in the range of 40-60 mg/day for a duration of 4-27 weeks prior to delivery. Both infants initially responded well to medical therapy for narcotic withdrawal, but at 7-14 days of age, withdrawal symptoms intensified, requiring an increase in the dosages of Paregoric (UDL Laboratories, Rockford, IL) and opium tincture in both infants and the addition of phenobarbital therapy in one infant. Both infants continued on medical therapy until they reached 1 month of age. Diazepam use by pregnant women can be associated with a later presentation of withdrawal symptoms in the neonate than that induced by the use of other drugs. Close follow-up during the first month of life is warranted for infants exposed to diazepam prenatally.

Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial.

OBJECTIVE: To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome. METHODS: Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation. RESULTS: The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age. CONCLUSIONS: In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.

Neonatal abstinence syndrome, pharmacotherapy and developmental outcome.

The majority of infants born to drug-dependent women undergo neonatal abstinence syndrome (NAS) and often require pharmacotherapy for the treatment of withdrawal symptoms. Phenobarbital, paregoric, and diazepam have been recommended for the treatment of the syndrome. While some investigators have examined the efficacy of these agents in treating NAS, there are no data regarding the use of specific pharmacologic agents and developmental outcome. This study evaluated 85 infants born to drug-dependent women who were maintained on methadone during pregnancy. Severity of infant withdrawal was assessed with the neonatal abstinence scoring system. Infants who required pharmacotherapy were randomly assigned to one of four treatment regimens: paragoric, phenobarbital (titration), phenobarbital (loading), and diazepam. When treatment was not successful with the assigned agent, one of the other agent(s) was used. At 6 months of age, the developmental status of infants was assessed with the Bayley Scales of Mental Development. Based on NAS treatment, four groups were defined: paregoric (n = 21); phenobarbital (n = 17); more than one agent (n = 31); and no treatment (n = 16). Data for the phenobarbital loading and titration groups were combined since analysis revealed no differences between groups. All infants who initially received diazepam were included in group III since diazepam as a single agent was not successful. Results of one way analysis of variance revealed no differences in developmental status between groups (p greater than 0.10, F = 0.25). Scores for all groups were well within the normal range of development.(ABSTRACT TRUNCATED AT 250 WORDS)

Narcotic addiction in the newborn: differences in behavior generated by methadone and heroin.

The nutritive sucking performance of congenitally addicted infants undergoing narcotic withdrawal was used to provide objective measures of adaptive behavior in a series of 50 infants born to mothers addicted either to heroin or methadone. Sucking rates as well as average pressures developed during sucking were significantly reduced for the addicted infants relative to a control group born to normal mothers and a second control group born to toxemic mothers. The subgroup of infants born to methadone-addicted mothers was significantly more depressed with regard to sucking behavior than the infants of heroin-addicted mothers. Furthermore, infants treated with paregoric (an opiate) for symptoms of the narcotic withdrawal syndrome showed significantly less depression of the sucking response than those treated with sedatives such as phenobarbital.

Diluted tincture of opium (DTO) and phenobarbital versus DTO alone for neonatal opiate withdrawal in term infants.

OBJECTIVE: The purpose of this study was to test the hypothesis that treatment of neonatal opiate withdrawal (NOW) in the term infant with diluted tincture of opium (DTO) and phenobarbital was superior to treatment with DTO alone. STUDY DESIGN: This was a partially randomized, controlled trial in which 20 term infants exposed to methadone and/or heroin in utero were studied. The severity of NOW was assessed by using the Finnegan scoring system. Infants were assigned to either DTO and placebo (n = 10) or DTO and phenobarbital (n = 10) when medication was required. The primary outcome variable was the duration of hospitalization. Severity of withdrawal and hospital cost were secondary outcome variables. RESULTS: There were no significant differences in the gestational age, growth variables, maternal methadone dose, or age at enrollment between the 2 groups. The duration of hospitalization was reduced by 48% (79-38 days) (P <.001) and hospital cost per patient reduced by $35,856 (P <.001) for the DTO and phenobarbital group. Furthermore, these infants spent less time with severe withdrawal (P <.04), more time with mild withdrawal (P <.03), and required a lower maximum daily DTO dose (P <.009) when compared with the DTO-only group. The average duration of outpatient phenobarbital use was 3.5 months. CONCLUSIONS: The combined use of DTO and phenobarbital resulted in a shorter duration of hospitalization, less severe withdrawal, and reduced hospital cost. This combination may be a preferred regimen for the treatment of NOW.