[Use of a new drug in the treatment of heroin addicts should not be obstructed by political dogmatism].
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Biomedical subjects
Publications and source records attributed to L Grönbladh.
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OBJECTIVE: To test the hypothesis that opiate addiction in adults might stem partly from an imprinting process during birth when certain drugs are given to the mother. DESIGN: Retrospective study by logistic regression of opiate addicts with siblings as controls. SETTING: Stockholm, Sweden. SUBJECTS: 200 Opiate addicts born in Stockholm during 1945-66, comprising 41 identified during interviews of probands for an earlier study; 75 patients whose death from opiate addiction had been confirmed during 1978-88; and 84 accepted for the methadone programme. 262 Siblings (controls) born in Stockholm during the same period, 24 of whom were excluded for drug addiction or being brought up outside the family. Birth records were unavailable for eight, leaving 230 siblings and 139 corresponding probands. MAIN OUTCOME MEASURES: Administration of opiates, barbiturates, and nitrous oxide (for greater than 1 h) to mothers of all subjects during labour within 10 hours before birth as a risk factor for adult opiate addiction. RESULTS: In subjects who had subsequently become addicts a significant proportion of mothers had received opiates or barbiturates, or both, compared with unmatched siblings (25% v 16%, chi 2 = 5.83, df = 1, p = 0.02), and these mothers had received nitrous oxide for longer and more often. After controlling for hospital of birth, order of birth, duration of labour, presentation other than vertex, surgical intervention, asphyxia, meconium stained amniotic fluid, and birth weight the relative risk for offspring subsequently becoming an adult opiate addict increased with the number of administrations of any of the three drugs. When the addicts were matched with their own siblings the estimated relative risk was 4.7 (95% confidence interval 1.8 to 12.4, p for trend = 0.002) for three administrations compared with when no drug was given. CONCLUSIONS: The results are compatible with the imprinting hypothesis. Therefore, for obstetric pain relief methods are preferable that do not permit substantial passage of drugs through the placenta.
The mortality within a cohort of 115 street heroin addicts was studied for 5-8 years using the Kaplan-Meier survival estimate technique. This differed markedly from the relatively low mortality of 166 comparable heroin addicts given methadone maintenance treatment (MT). The street addicts' mortality rate was 63 times that expected, compared with official statistics for a group of this age and sex distribution. When 53 patients in MT were involuntarily expelled from treatment, due to violation of programme rules, they returned to the high mortality of street addicts (55 times that expected). A group of 34 rehabilitated patients who left MT with medical consent retained the low mortality of MT patients (their mortality rate was 4 times that expected). Despite this great improvement in survival, even patients in MT showed a moderately elevated mortality (8 times that expected), mainly due to diseases acquired before entering the treatment programme. It is concluded that MT exerts a major improvement in the survival of heroin addicts.
During its first 20 years of existence a national Swedish methadone maintenance programme received 174 heroin addicts. Programme policy, with a massive emphasis on vocational rehabilitation, and outcome data are described. In 75% of the cases the subjects abandoned their drug abuse behaviour and took up work while 25% were expelled from the programme due to violation of rules. The stability of the programme was established by 14 yearly check-ups of the percentage working and studying, which remained about 80%. The tendency towards maturing out of addiction was low in Swedish heroin addicts (6%) as evidenced by a special study including a 6-year follow-up of 34 subjects fulfilling admission criteria. Half of this group received methadone, while the other half were randomly assigned controls. The death rate among controls was at least 73 times the expected for the age group studied (20-24 years), while 81% of those receiving methadone became free of drug abuse and vocationally rehabilitated. The control group also showed a high rate of drug abuse-related morbidity. Among 34 female heroin addicted prostitutes 71% abandoned drugs and street prostitution and took up regular work.
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Deuterated methadone (M-d3) and GC-MS analysis were used to study the steady state pharmacokinetics of methadone (M) in eight patients reported as therapeutic failures in a methadone maintenance treatment programme. The patients were compared to an unselected group of 12 patients stabilized on M for 25 days. During one dosage interval a pulse dose of M-d3 was administered intravenously instead of the oral M-dose (M-d0). The pharmacokinetic parameters, half-life in the beta-phase (t1/2 beta), volume of distribution during the postdistributive phase (Vd beta) and during steady state (Vdss) were determined as well as the body (ClS) and renal (ClR) clearances of M. Pronounced differences in Vd beta and Vdss were found between the two groups. The therapeutic failures had a smaller Vd beta and Vdss 3.09 +/- 0.96 1/kg and 2.74 +/- 0.96 1/kg vs 4.56 +/- 1.00 1/kg and 4.20 +/- 0.78 1/kg in the control group. The differences were due to changes between the groups in the volume of the central compartment. Differences between the groups were also found in t1/2 beta - 24.5 +/- 2.6 h in the therapeutic failures and 34.0 +/- 7.0 h (p less than 0.001) in the comparison group. However, the change in t1/2 beta was probably a consequence of the change in Vd beta, as the body clearance of M was similar in the two groups - 104 +/- 36 ml/min vs 111 +/- 36 ml/min. The smaller volume of distribution could lead to unacceptably high fluctuation of M in the central compartment, and withdrawal symptoms during the latter part of the dosage interval.(ABSTRACT TRUNCATED AT 250 WORDS)
Thirty-four drug addicts, aged 20 - 24 years, with a history of 4 - 8 years of intravenous heroin abuse, were randomly assigned either to a methadone maintenance treatment (MMT) (17) or to an untreated group (17). The untreated controls could not apply for entrance to the program until two years later. It was found that after two years 12 MMT patients had abandoned their drug habits and begun work, whereas 5 had recurrent drug abuse problems. Of the controls, one was drug-free and gainfully employed, 12 were continuously abusing heroin (3 of these had incurred potentially fatal diseases in consequence), 2 were in prison and 2 had diet. Two to seven years after their first visit to the Psychiatric Research Center 8 of the original control group have been accepted into the program. At present 19 (out of 25 admitted) are gainfully employed and no longer abusing drugs. Among the remaining controls 4 are dead, 3 are in prison, one in spite of a serious heart condition abuses heroin and one is drug-free. The rehabilitation rate was thus 76 per cent in the program as compared to 6 per cent among the control group. In addition, MMT obviously reduced the high morbidity and mortality rates found in a selection of heroin addicts who fulfilled the admittance criteria of the Swedish program.
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