Comorbidity is highly prevalent in CMHT, drug and alcohol treatment populations, but may be difficult to manage by cross-referral psychiatric and substance misuse services as currently configured and resourced.

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The validity of the general neurotic syndrome, a combination of anxiety, depression and dependent personality disorder, was examined in a 2-year study of outpatients with dysthymic, panic and generalized anxiety disorder diagnosed using a structured interview schedule. The general neurotic syndrome, found in a third of the patients, was associated with greater mental disorder and a significantly worse outcome than patients without the syndrome. It did not, however, predict response to treatment. Further analysis revealed that the general neurotic syndrome was a better predictor of short- and long-term outcome than any other variable apart from initial psychopathology score. It is argued that the syndrome may represent a personality diathesis that makes the individual more vulnerable to both anxiety and depressive symptoms.

In both alcohol and drug service populations, personality disorder is associated with significantly increased rates of psychopathology and social morbidity that worsens with increasing severity of the disorder. Despite this, personality disorder is poorly identified by clinical staff. The PAS-Q may be useful as a clinical assessment tool in the substance misuse population for the early identification and management of patients with personality disorder.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Several cytochromes P450 (CYPs) have been implicated in the metabolism of methadone, but there is no consensus on their relative contributions to overall disposition and hence variability in response. WHAT THIS STUDY ADDS• Variability in CYP3A4 activity has statistically significant but nonetheless modest influence on the oral clearance of methadone and its enantiomers. • However, CYPs 1A2 and 2D6 appear to have no impact at all. AIMSTo 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). METHODSEighty-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). Data on all three CYPs were obtained from 32 subjects. Total plasma concentrations of (RS)-methadone and total and unbound plasma concentrations of both enantiomers were measured by LC/MS. Population pharmacokinetics and subsequent multiple regression analysis were used to calculate methadone oral clearance and to identify its covariates. RESULTSBetween 61 and 68% of the overall variation in total plasma trough concentrations of (RS)-, (R)-and (S)-methadone was explained by methadone dose, duration of addiction before starting MMT, CYP3A activity and illicit morphine use. CYP3A activity explained 22, 16, 15 and 23% of the variation in unbound (R)-, unbound (S)-, total (RS)-and total (S)-methadone clearances, respectively. Neither CYP2D6 nor CYP1A2 activity was related to methadone disposition. CONCLUSIONSCYP3A activity has a modest influence on methadone disposition. Inhibitors and inducers of this enzyme should be monitored in patients taking methadone.