A six-year evaluation of methadone prescribing practices at a substance misuse treatment centre in the UK.

OBJECTIVES: To document changes in prescribing practice at a specialized substance misuse service in the UK occurring since the introduction of the 1999 UK National Guidelines on the management of drug misuse, and to explore a possible link between the length of time spent in methadone maintenance therapy (MMT) and the dosage prescribed. METHODS: A retrospective analysis of a computerized prescription database between 1996 and 2002 obtained from Sheffield Care Trust Substance Misuse Service was performed. The relationship between various measures of dosage and the length of time spent in MMT was investigated. RESULTS: In accordance with the 1999 UK National Guidelines, the proportion of injectable methadone prescribed decreased from 22% to 16%. This was offset by an increase in the prescribing of methadone elixir from 74% to 79%. The 'maximum dose' of methadone prescribed correlated significantly with patient retention, explaining 14% of the variation in time spent in MMT. CONCLUSIONS: Our findings indicate that publication of the UK National Guidelines had a measurable effect on prescribing practice at the Service. We found that a higher methadone dose is associated with increased patient retention in MMT. However, as only a maximum of 14% of the variation in the length of stay is related to methadone dose, the importance of other aspects of treatment such as counselling and rehabilitation programmes, should be considered for the successful treatment of opioid abusers.

A discordance between cytochrome P450 2D6 genotype and phenotype in patients undergoing methadone maintenance treatment.

AIMS: To assess CYP2D6 activity and genotype in a group of patients undergoing methadone maintenance treatment (MMT). METHODS: Blood samples from 34 MMT patients were genotyped by a polymerase chain reaction-based method, and results were compared with CYP2D6 phenotype (n = 28), as measured by the molar metabolic ratio (MR) of dextromethorphan (DEX)/dextrorphan (DOR) in plasma. RESULTS: Whereas 9% of patients (3/34) were poor metabolizers (PM) by genotype, 57% (16/28) were PM by phenotype (P < 0.005). Eight patients, who were genotypically extensive metabolizers (EM), were assigned as PM by their phenotype. The number of CYP2D6*4 alleles and sex were significant determinants of CYP2D6 activity in MMT patients, whereas other covariates (methadone dose, age, weight) did not contribute to variation in CYP2D6 activity. CONCLUSIONS: There was a discordance between genotype and in vivo CYP2D6 activity in MMT patients. This finding is consistent with inhibition of CYP2D6 activity by methadone and may have implications for the safety and efficacy of other CYP2D6 substrates taken by MMT patients.

The profile of C-reactive proteins in functional psychotic states in a cohort in Nigeria.

Based on the findings of previous work involving the measurement of 8 acute-phase proteins in 8 subjects receiving electroconvulsive therapy, we assayed the levels of C-reactive proteins (CRP) in 40 functional psychotic subjects, 37 of whom were consecutive admissions at the psychiatric ward. From 16 subjects, a second sample of blood for assay of CRP was collected 6 weeks after discharge from hospital, when the patients were no longer experiencing psychotic symptoms. The patients and controls were screened for tissue injury, inflammatory conditions and other diseases. We found that 14 (35%) of the psychiatric patients and only one (2%) of 50 normal control subjects had detectable levels of CRP. At follow-up, none of the 7 patients in whom CRP had been earlier detectable had measurable levels of CRP in the non-psychotic state. The presence of CRP was not related to biochemical indexes of nutritional status (total proteins and albumin), nor did clinical variables such as type of psychosis, pacing in acutely disturbed patients, use of intramuscular injections or diet and drugs distinguish the two groups of patients. It is suggested that the presence of CRP in the psychotic state is probably a state-dependent expression of nonspecific humoral immune alteration in subjects in whom more specific tests could reveal some immune alteration.