Worsening of obsessive-compulsive symptoms under methadone tapering.

There is data supporting the hypothesis that the endogenous opioid system may play a role in the pathophysiology of Obsessive Compulsive Disorder (OCD). The authors report a case of worsening of OCD during methadone tapering, which seems to confirm the role of the opioid system in the pathophysiology of OCD. The possible involvement of the cortico-limbic-basal-ganglia-thalamic circuit in the observed phenomenon is discussed.

[Medical management of drug addicts in the prison system in Vaud]. / Prise en charge médicale des personnes toxicodépendantes dans le système pénitentiaire vaudois.

Despite the improvement and the diversification of the circuits for care in the city, the number of drug addicts sentenced to prison sentences in the Canton of Vaud in Switzerland has not decreased in recent years. It is therefore imperative for the Prison Medicine and Psychiatry Service (SMPP) to provide a medical follow up which respects as closely as possible the principle of the equivalence of care with the outside environment. This article presents the way in which the SMPP takes its place in the continuity of the therapeutic assistance which drug dependent individuals can take advantage of. In this way, the range of therapeutic protocols in force in the different regimes of detention (preventive detention, custody and the execution of sentence) are examined, whether initial treatment, drug weaning or substitution therapies.

Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone.

BACKGROUND AND OBJECTIVES: Cytochrome P450 (CYP) 3A4 is the main CYP isozyme involved in methadone metabolism. We investigated the influence of grapefruit juice, which contains inhibitors of intestinal CYP3A, on the steady-state pharmacokinetics of methadone. METHODS: For 5 days, 8 patients undergoing methadone maintenance treatment received 200 mL water or grapefruit juice 30 minutes before and again together with their daily dose of methadone. Blood sampling for R-, S-, and R,S-methadone plasma determination was performed over a 24-hour period. CYP3A activity was determined by measuring the plasma 1'-hydroxymidazolam/midazolam ratio. RESULTS: A decrease in the midazolam ratio was measured in all patients after grapefruit juice (mean +/- SD before grapefruit juice, 9.3 +/- 5.9; mean +/- SD after grapefruit juice, 3.9 +/- 1.2; P <.05). Grapefruit juice led to a mean 17% increase in the area under the curve extrapolated to 24 hours for both enantiomers of methadone (range, 3% to 29% [P <.005]; range, -4% to 37% [P <.05]; and range, 1% to 32% [P <.01]; for R-, S-, and R,S-methadone, respectively). A similar increase in peak level and decrease in apparent clearance were measured with grapefruit juice, whereas time to peak level, terminal half-life, and apparent volume during the terminal phase of R-, S-, and R,S-methadone were not affected by grapefruit juice. No symptom of overmedication was either detected by the clinical staff or reported by the patients. CONCLUSIONS: Grapefruit juice administration is associated with a modest increase in methadone bioavailability, which is not expected to endanger patients. However, it cannot be excluded that a much stronger effect may occur in some patients, and thus grapefruit juice intake is not recommended during methadone maintenance treatment, in particular in patients initiating such a treatment.