The Leeds Dependence Questionnaire (LDQ) has been developed as part of a treatment evaluation package. The LDQ is a 10-item, self completion questionnaire designed to measure dependence upon a variety of substances; it has been shown to be understood by users of alcohol and opiates. The questionnaire was designed to be sensitive to change over time and to be sensitive through the range from mild to severe dependence; the follow-up data are insufficient to demonstrate change over time, but are encouraging. It is expected that both clinicians and researchers will find it useful to have a single measure relating to substance use, but not limited by specific substances. All items are scored 0-1-2-3; there are no normative data. The procedure for establishing content validity is described and estimates of concurrent, discriminant and convergent validities are reported; these validities are thought to be satisfactory. A principal components analysis produced a single factor accounting for 64% of the variance. Cronbach's alpha was 0.94. Test-retest reliability was found to be 0.95.
This paper is an interim report describing the development of a 15-item, self-completion questionnaire designed to measure Alcohol Dependence. Some measures of reliability are also presented.
The client's personal drinking goals should be discussed in assessment at treatment entry and as a basis for negotiation. Clinicians should be prepared to identify and support goal change as an unexceptional part of the treatment process that need not jeopardize good outcome.
The implications of these findings for service delivery are best considered in conjunction with findings from a companion paper reporting treatment outcomes associated with each goal preference.
Aims Although methadone is widely used to treat opiate dependence, guidelines for its dosage are poorly defined. There is increasing evidence to suggest that a strategy based on plasma drug monitoring may be useful to detect non-compliance. Therefore, we have developed a population-based pharmacokinetic (POP-PK) model that characterises adaptive changes in methadone kinetics. Methods Sparse plasma rac-methadone concentrations measured in 35 opiate-users were assessed using the P-Pharm software. The final structural model comprised a biexponential function with first-order input and allowance for time-dependent change in both clearance (CL) and initial volume of distribution ( V ). Values of these parameters were allowed to increase or decrease exponentially to an asymptotic value. Results Increase in individual values of CL and increase or decrease in individual values of V with time was observed in applying the model to the experimental data. Conclusions A time-dependent increase in the clearance of methadone is consistent with auto-induction of CYP3A4, the enzyme responsible for much of the metabolism of the drug. The changes in V with time might reflect both up-and downregulation of a 1 -acid glycoprotein, the major plasma binding site for methadone. By accounting for adaptive kinetic changes, the POP-PK model provides an improved basis for forecasting plasma methadone concentrations to predict and adjust dosage of the drug and to monitor compliance in opiate-users on maintenance treatment.
Aims There is some evidence that monitoring methadone plasma concentration may be of benefit in dosage adjustment during methadone maintenance therapy for heroin (opiate) dependence. However, the kinetics of oral methadone are incompletely characterized. We attempted to describe the latter using a population approach combining intensive 57 h sampling data from healthy subjects with less intensive sparse 24 h data from opiate users.
Methods Single oral doses of rac‐methadone were given to 13 drug‐naive healthy subjects (7 men and 6 women) and 17 opiate users beginning methadone maintenance therapy (13 men and 4 women). Plasma methadone concentrations were measured by h.p.l.c. Kinetic analysis was performed using the P‐Pharm software.
Results Comparison of kinetic models incorporating mono‐ or biexponential disposition functions indicated that the latter best represented the data. The improvement was statistically significant for the data from healthy subjects whether the full 57 h or truncated 24 h profiles were used (P<0.031 and P<0.024, respectively), while it was of borderline significance for the more variable data from opiate users (P=0.057) or for pooled (healthy subjects and opiate users) data (P=0.066). The population mean oral clearance of methadone was 6.9±1.5 s.d. l h−1 (5.3±1.2 s.d. l h−1 using 0–24 h data) in the healthy subjects. The results of separate analyses of the data from opiate users and healthy subjects were in contrast with those obtained from pooled data analysis. The former indicated a significantly lower clearance for opiate users (3.2±0.3 s.d. l h−1, P<0.001); 95% CI for the difference=−3 to −6 l h−1 and no difference in the population mean values of V /F (212±27 s.d. l and 239±121 s.d. l, P=0.15), while according to the latter analysis addiction was a covariate for V /F but not for oral clearance. A slower absorption of methadone in opiate users was indicated from the analysis of both pooled and separate data. The median elimination half‐life of methadone in healthy subjects was 33–46 h depending on the method used to calculate this parameter.
Conclusions Estimates of the long terminal elimination half‐life of methadone (33–46 h in healthy subjects and, possibly, longer in opiate users) indicated that accurate measurement of this parameter requires a duration of sampling longer than that used in this study. Our analysis also suggested that parameters describing plasma concentrations of methadone after a single oral dose in healthy subjects may not be used for predicting and adjusting dosage in opiate users receiving methadone maintenance therapy unless coupled with feedback concentration monitoring techniques (for example Bayesian forecasting).
The evidence for the unitary nature of alcohol dependence is discussed and the usefulness of existing instruments to measure dependence is reviewed. Three separate studies are presented that support the validity of SADD. Several measures of construct and concurrent validity are investigated including comparison with the SADQ and EADS. Attention is drawn to the discriminating characteristics of SADD in the mild/moderate dependence range.
General Practitioners and hospital doctors should recognise the significant benefits of prescribing methadone for heroin-dependent women during pregnancy. We recommend that if a pregnant opioid user complains of methadone withdrawal symptoms (i.e. that the methadone dose does not "hold" them) the prescribing clinician takes this observation seriously and considers a more detailed assessment. Further work on key factors undergoing changes during pregnancy accounting for differences in methadone metabolism in the mother, fetus and neonate are required.
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