High-dose Methadone Research Articles

Prenatal administration of methadone using the osmotic minipump: Effects on maternal and offspring toxicity, growth, and behavior in the rat

Two doses of methadone were administered by osmotic minipump from day 8 of gestation through parturition. A pair-fed control group received saline via minipump and was allowed to eat and drink only the amount consumed by the high dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Naloxone challenge of the dams after parturition showed that drug treatment produced physical dependence. Methadone treatment reduced maternal weight gain but had no effect on either the frequency of resorptions or birthweight. Both doses of methadone increased perinatal mortality but only the high dose produced a decrement in postnatal growth. To examine the effects of methadone on the rest-activity cycle of the offspring, groups of three littermates from each of the treated and control groups were tested for an 8 h observation period on electronic activity monitors at 22 days of age. No behavioral effects were observed for either control group or the low dose methadone group. The high dose methadone offspring, however, spent less time resting, showed disrupted rhythmicity, and poor state regulation. These findings are discussed in relation to earlier studies using once per day methadone administration as well as clinical descriptions of infants undergoing opiate abstinence.

Sexual Dysfunction and Psychological Distress in Methadone Maintenance

We administered the Derogatis Sexual Functioning Inventory to 25 methadone maintenance patients who had been on a stable dose of methadone for at least 2 months, and obtained ratings of depression and anxiety, levels of sex hormones, and liver function tests. Five subjects with significantly lower Global Sexual Satisfaction Index scores (p < .0001) had more psychological symptoms, higher methadone doses, poorer body image, and less sexual drive and satisfaction, but normal fund of sexual information and lifetime experience. Sexual dysfunction among methadone maintenance patients may be due to coexisting psychiatric problems rather than caused by opiates. Methadone patients presenting with sexual dysfunction should receive psychiatric evaluation.

High-dose methadone and the need for drug measurements in plasma

We report a case of high-dose methadone prescribed to a heroin addict for pain control. The patient was prescribed methadone during convalescence from surgery and subsequently for maintenance treatment. Dosing was started at 360 mg of methadone per day and reduced over 12 days to an 80 mg/day maintenance dose. Although the patient was drowsy on the initial dose, his recovery was uneventful. However, there were complaints of pain and withdrawal discomfort when the plasma concentration decreased to less than 1 mg/L. Measurements of methadone in plasma were helpful for monitoring the recovery of this patient after surgery and are likely to prove useful in similar cases.

Inadequate plasma concentrations in some high-dose methadone maintenance patients.

The author studied 18 heroin addicts who had been maintained on 80 mg/day of methadone and who abused drugs or alcohol. His findings suggest that in some cases of aberrant methadone metabolism, the dose can be raised to achieve plasma concentrations adequate to eliminate drug and alcohol abuse.

Chronic opiate use during methadone detoxification: Effects of a dose increase treatment

The effects of administering high methadone doses during detoxification treatment were examined on illicit opiate use and treatment retention in chronic opiate supplementors. Twenty-six applicants to a 90-day outpatient detoxification program who delivered 50% or more opiate-positive urine samples during treatment weeks 2 and 3 were randomly assigned to receive a constant 30-mg dose through treatment week 10 or an increase to 60 mg in week 4 with gradual reduction to 30 mg by week 10. Dosage for both groups was reduced to 0 mg during weeks 11–13. Treatment retention was better for experimental (median = 86 days) than for control (median = 41 days) subjects, but the difference was not statistically significant. In the dose increase group, percent opiate-positive urines decreased from 80% to 62% during the first two weeks of dose increase ( t = 2.39, P < 0.05); opiate positive rates for the control group remained above 80%. A 20% between group difference in percent of opiate positive urine tests persisted through study week 10 in subjects ( N = 5 control, 7 experimental) who remained in treatment this long. Although the blind dose increase did improve treatment outcome, we concluded that the magnitude of the effect in this population of chronic opiate supplementors was insufficient to judge the procedure clinically useful.

In utero exposure to methadone produces a stable decrease of the cortex 5-HT transport system in rats

Female rats were made dependent to high doses of morphine (400 mg/kg per day) or methadone (60–80 mg/kg per day) and subsequently exposed to adult males. None of the morphine-dependent rats became pregnant while there were no differences in the gestation time and number of young in the litter born to each rat in the methadone and the control groups. The values for muscarninic, serotonergic and opiate receptors measured in the whole brain of the offspring at 1 and 7 days after birth were similar in the control and in the methadone-exposed animals. Brain β-receptors were lower in rats exposed in utero to methadone at 1 and 7 days. [ 3H]IMI binding sites were steadily and significantly lower in the whole brain of rats born to methadone-dependent animals than in the brain of controls. In 2 month old animals, the decrease of [ 3H]IMI binding capacity was associated with a decrease of [ 3H]5HT uptake. In the light of these findings the authors propose a unifying hypothesis to explain the altered reactivity to morphine of animals treated with opiates during gestation.

Sustained attention in methadone patients.

Sustained attention was examined in chronic, high-dose (70-120 mg) methadone patients with a modified Continuous Performance Test (Rosvold et al., 1956) 45 min in duration. Working and nonworking patient groups, and drug-free ex-addict and opiate-naive comparison groups were tested at high, moderate, and low signal rates. Groups did not differ overall in accuracy, response latencies, or commission errors. The working patients, however, performed better at the high than at the lower signal rates, and had poorer accuracy and longer latencies at the low rate than the comparison groups. The nonworking patients had different results; they made more commission errors at the high signal rate than the other three groups.

Methadone Patients: Dosage, Psychopathology, and Research Participation

High and low dose methadone patients from a private methadone clinic were studied to determine whether severity of psychopathology is correlated with methadone dosage. It was found that methadone dosage was not positively correlated with psychopathology, but that diffuse nonspecific psychopathology was observed in all participants. Despite financial incentives it was very difficult to obtain the participation of many individuals in the clinic, and those who agreed to participate saw the research as a means to obtain personal psychiatric treatment. This differential participation based on viewing the research as "therapeutic" must be considered in future evaluation of methadone treatment.

Methadone Dose and Human Sexual Behavior

Among 31 male and 17 female former addicts in methadone maintenance or drug-free treatment, the frequency of sexual behaviors was determined by questionnaires administered at least weekly over several weeks. Daily methadone dose (mg/kg) correlated significantly with frequency of genital contacts (r = -.54) and organs (-.43) among females, and with frequency of ejaculation (-.31) among males. Although open and nonblind, the study suggests that higher doses of methadone may suppress human sexual behavior.

Maintenance Dosage as a Critical Factor in Methadone Maintenance Treatment*

AbstractThis study concentrates on methadone dosage as a critical factor influencing abuse of other psychoactive drugs (including alcohol) by patients maintained on methadone. The study population were patients who remained on methadone for at least two years. The effects of dosage level on a group of 46 patients (low dosage n=27, ×= 48.32; high dosage n = 19, ×= 86.43) is reported. Significant increases (p &lt; 0.01) were found in the abuse of barbiturates, ataractics, and alcohol for the low dosage group. Dosage level had no significant relationship with heroin and amphetamine abuse. These results suggest that higher doses of methadone may provide the patients with a generalized central nervous system depressive effect.

Digit-symbol performance in methadone-treated ex-heroin addicts

The digit-symbol substituion task (DSST) of the WAIS was given to working (MW) and nonworking (MNW) patients on high-dose methadone maintenance and to two comparison groups to assess the function of attention in these patients. Mean DSST scores were significantly lower for the MNW group than for the other three groups, which did not differ. However, the scores for the MNW group were within the normal range. DSST scores and lenght of methadon treatment (range: 11 months to 8 years) were positively correlated, providing no evidence of deterioration with increasing duration of treatment.

Long-term methadone maintenance therapy: effects on liver function.

To determine whether chronic high-dose (80 to 120 mg/day) methadone treatment would exert hepatotoxic effects on patients with or without liver disease, the first 214 patients admitted for maintenance therapy were studied prospectively; 129 were still in treatment after 3 or more years. There were no significant changes in tests of liver function with time and, therefore, no evidence of methadone hepatotoxicity. Of the group 23% had a history of hepatitis, and 25% were moderate to heavy users of ethanol. Minimal to moderate abnormalities of liver function tests were present in 57% at admission and in 51% after 3 or more years of treatment. Up to 49% had abnormalities in some protein tests throughout. The liver function abnormalities may be caused by chronic persistent or, less frequently, chronic aggressive hepatitis and, in some, by excessive usage of ethanol. Protein abnormalities may be owing to liver disease and altered immune status caused by injection of foreign substances.