Pharmacokinetic-pharmacodynamic modeling of mood and withdrawal symptoms in relation to plasma concentrations of methadone in patients undergoing methadone maintenance treatment.

The aims of the present study were to characterize the relationship between plasma racemic methadone and its enantiomers' concentrations with respect to their pharmacodynamic effects and to investigate the influence of potential covariates on the pharmacodynamic parameters in patients on methadone maintenance treatment (MMT). Eighty-eight regular subjects at the Sheffield Care Trust Substance Misuse Services were studied. Samples of blood and urine were collected before the daily dose of methadone.

Contribution of the activities of CYP3A, CYP2D6, CYP1A2 and other potential covariates to the disposition of methadone in patients undergoing methadone maintenance treatment.

Aims: To investigate the influence of different cytochrome P450 (CYP) activities and other potential covariates on the disposition of methadone in patients on methadone maintenance therapy (MMT).

Methods: Eighty-eight patients (58 male; 21-55 years; 84 White) on MMT were studied. CYP2D6 activity [3 h plasma metabolic ratio of dextromethorphan (DEX) to dextrorphan (DOR)] was determined in 44 patients (29 male; 24-55 years), CYP1A2 activity (salivary caffeine elimination half-life) in 44 patients (21 male; 24-55 years) and CYP3A activity (oral clearance of midazolam) in 49 patients (33 male; 23-55 years).

Post-treatment outcomes of buprenorphine detoxification in community settings: a systematic review.

A systematic review was undertaken to examine studies of buprenorphine detoxification that has included post-treatment outcomes as well as more immediate aspects of progress. Studies were required to report details of buprenorphine withdrawal regime and post-treatment outcomes including abstinence rates. Only five studies met these criteria, with buprenorphine regimes lasting 3 days to several weeks, and with variable follow-up.

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.

Personality disorder and drug use: a review.

The concept of personality disorder (PD) is more relevant in the clinical management of drug users than other approaches to personality assessment. A problem in diagnosis is separating behaviours inherent in the activity of drug misuse from true evidence of PD, especially the anti-social type (ASPD), and rating instruments vary in their ability to do this. Nevertheless, the available evidence suggests that approximately two-thirds of drug users in treatment have PD, with ASPD the most common.

Can saliva replace plasma for the monitoring of methadone?

The aims of this study were to determine the relationship between saliva and plasma methadone concentrations and the influence of variability in saliva pH. Saliva and plasma samples were taken before the daily dose of methadone in 60 patients undergoing methadone maintenance treatment (MMT). Saliva pH was measured immediately after sampling, and concentrations of (RS)-, (R)-, and (S)-methadone in saliva and plasma were assayed by LC/MS.

Prevalence of personality disorder in alcohol and drug services and associated comorbidity.

Aims: To compare the prevalence of personality disorder in alcohol and drug populations with special attention to its impact on psychopathology and service characteristics.

Design: Cross-sectional survey.

Setting: Three alcohol and four drug services in four urban UK centres.

Comorbidity of substance misuse and mental illness in community mental health and substance misuse services.

Background: Improved management of mental illness and substance misuse comorbidity is a National Health Service priority, but little is known about its prevalence and current management.

Aims: To measure the prevalence of comorbidity among patients of community mental health teams (CMHTs) and substance misuse services, and to assess the potential for joint management.

Method: Cross-sectional prevalence survey in four urban UK centres.

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.

Prescribing to drug misusers in practice--often effective, but rarely straightforward.

Many reviews describe the effectiveness of methadone treatment in reducing illicit drug use and associated behaviours among opiate misusers. The strongest evidence includes social outcomes such as reduced debt and crime, and relates overwhelmingly to maintenance rather than detoxification treatment. Drug clinics are often dominated by individuals unable to withdraw fully from methadone, while the "harm reduction" model accepts some ongoing drug use, with attendant risks.

Cocaine misuse treatment in England.

Three methods were used to identify the treatments given to cocaine misusers in England, and to make a preliminary assessment of effectiveness. First, a postal survey of all known drug misuse treatment services ascertained approximate numbers of cocaine misusers presenting and receiving a specified range of treatments. Secondly, staff at selected services were interviewed regarding treatment policies, and asked to subjectively rate short-term and long-term effectiveness.

Longitudinal study of the influence of life events and personality status on diagnostic change in three neurotic disorders.

It has been known for many years that diagnosis within the neurotic spectrum of disorders is temporally unstable and also that life events can be major precipitants of change in symptoms. Reasons for this instability could include inherent inadequacy of current diagnostic practice, the influence of life events as an agent of diagnostic shift, and an innate course of disorder with features dependent on the stage at which disorder presents (e.g.

Can methadone maintenance for heroin-dependent patients retained in general practice reduce criminal conviction rates and time spent in prison?

A retrospective analysis was made of the criminal records of 57 patients successfully retained in methadone maintenance at two general practices in Sheffield. Their criminal conviction rates and time spent in prison per year were compared for the periods before and after the start of their methadone programme. Overall, patients retained on methadone programmes in the general practices studied had significantly fewer convictions and cautions, and spent significantly less time in prison than they had before the start of treatment.

Long-term outcome of hypochondriacal personality disorder.

Hypochondriacal personality disorder diagnosed according to the Personality Assessment Schedule, a structured clinical interview, was related to outcome after 2 years and 5 years in a randomized, controlled trial of treatment of generalized anxiety, panic, and dysthymic disorders. Seventeen individuals (9%) from a population of 181 patients had hypochondriacal personality disorder and they experienced a significantly worse outcome than other patients, including those with other personality disorders, in terms of symptomatic change and health service utilization. This lack of improvement was associated with persistent somatization in hypochondriacal personality disorder.

The Nottingham Study of Neurotic Disorder: influence of cognitive therapists on outcome.

Background: In previously published papers from the Nottingham Study of Neurotic Disorder a short treatment package of cognitive-behaviour therapy was no more effective than placebo drug treatment after 10 weeks' assessment in a cohort of 210 patients with neurotic disorders. This paper examines the outcome over two years of the patients treated by cognitive-behaviour therapy separated into two therapist groups, those who were competent in administering treatment and those of uncertain competence.

Method: The therapists (mainly community psychiatric nurses) of 70 patients with an original DSM-III diagnosis of either dysthymic, panic or generalised anxiety disorder were separated into two groups on the basis of their perceived competence by their supervisor (DK).

Withdrawal symptoms from high dose benzodiazepines in poly drug users.

Among poly drug users attending a treatment service, 33 subjects were identified who had experienced withdrawal symptoms from high dose benzodiazepines (median diazepam equivalent 140 mg/day) at a time uncomplicated by simultaneous cessation of other drugs. Symptoms were rated using the Benzodiazepine Withdrawal Symptom Questionnaire (Tyrer et al. (1990) The Benzodiazepine Withdrawal Symptom Questionnaire.

The Nottingham study of neurotic disorder. Effect of personality status on response to drug treatment, cognitive therapy and self-help over two years.

Repeated assessments of psychopathology, together with personality status, were made over two years on 181 psychiatric out-patients with generalised anxiety disorder (59), panic disorder (66), or dysthymic disorder (56) diagnosed using an interview schedule for DSM-III. Patients were randomly allocated to drug treatment, cognitive and behaviour therapy, or a self-help treatment programme. Although there were no overall differences in compliance rate and efficacy between the three modes of treatment, the psychological treatment methods, particularly self-help, were more effective in patients without personality disorder, and those with personality disorder responded better to drug treatment, primarily antidepressants.