Multidimensional family therapy reduces problematic gaming in adolescents: A randomised controlled trial.

BACKGROUND AND AIMS: Social variables including parental and family factors may serve as risk factors for Internet Gaming Disorder (IGD) in adolescents. An IGD treatment programme should address these factors. We assessed two family therapies - multidimensional family therapy (MDFT) and family therapy as usual (FTAU) - on their impact on the prevalence of IGD and IGD symptoms. METHODS: Eligible for this randomised controlled trial comparing MDFT (N = 12) with FTAU (N = 30) were adolescents of 12-19 years old meeting at least 5 of the 9 DSM-5 IGD criteria and with at least one parent willing to participate in the study. The youths were recruited from the Centre Phénix-Mail, which offers outpatient adolescent addiction care in Geneva. Assessments occurred at baseline and 6 and 12 months. RESULTS: Both family therapies decreased the prevalence of IGD across the one-year period. Both therapies also lowered the number of IGD criteria met, with MDFT outperforming FTAU. There was no effect on the amount of time spent on gaming. At baseline, parents judged their child's gaming problems to be important whereas the adolescents thought these problems were minimal. This discrepancy in judgment diminished across the study period as parents became milder in rating problem severity. MDFT better retained families in treatment than FTAU. DISCUSSION AND CONCLUSIONS: Family therapy, especially MDFT, was effective in treating adolescent IGD. Improvements in family relationships may contribute to the treatment success. Our findings are promising but need to be replicated in larger study. TRIAL REGISTRATION NUMBER: ISRCTN 11142726.

Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval.

BACKGROUND: Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. METHODS: To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R)-methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. RESULTS: The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). CONCLUSIONS: Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death.

Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study.

PURPOSE: To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics. METHODS: Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose. RESULTS: Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4. CONCLUSION: Cannabis use and higher methadone doses in MMT could in part be a response to-or a cause of-more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT.

Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment.

BACKGROUND: Genetic variations of the dopamine and opioid receptors could influence the response to methadone maintenance treatment (MMT). METHODS: We included 238 MMT patients according to their response to treatment and methadone dosing, along with 217 subjects without substance dependence. All were genotyped for polymorphisms of the dopamine D1, D2, micro-opioid and delta-opioid receptor genes. RESULTS: The polymorphisms of the micro-opioid (118A>G), delta-opioid (921T>C), dopamine D1 (DdeI) and D2 (TaqI A) receptor genes were not associated with response to MMT and methadone dosing, whereas an association was found with the dopamine D2 receptor (DRD2) 957C>T polymorphism. The 957CC carriers were more frequently non-responders to treatment (OR=2.4; p=0.02) and presented a fourfold shorter period of negative urine screening (p=0.02). No significant differences in allele frequencies were observed between the MMT patients and the control group, suggesting no association of the analyzed polymorphisms with opioid dependence. CONCLUSIONS: These results suggest that DRD2 genotype may contribute to the understanding of the interindividual variability to the response to MMT.

ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment.

BACKGROUND AND OBJECTIVE: The in vivo implication of various cytochrome P450 (CYP) isoforms and of P-glycoprotein on methadone kinetics is unclear. We aimed to thoroughly examine the genetic factors influencing methadone kinetics and response to treatment. METHODS: Genotyping for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, ABCB1, and UGT2B7 polymorphisms was performed in 245 patients undergoing methadone maintenance treatment. To assess CYP3A activity, the patients were phenotyped with midazolam. RESULTS: The patients with lower CYP3A activity presented higher steady-state trough (R,S)-methadone plasma levels (4.3, 3.0, and 2.3 ng/mL x mg for low, medium, and high activity, respectively; P = .0002). As previously reported, CYP2B6*6/*6 carriers had significantly higher trough (S)-methadone plasma levels (P = .0001) and a trend toward higher (R)-methadone plasma levels (P = .07). CYP2D6 ultrarapid metabolizers presented lower trough (R,S)-methadone plasma levels compared with the extensive or intermediate metabolizers (2.4 and 3.3 ng/mL x mg, respectively; P = .04), whereas CYP2D6 poor metabolizer status showed no influence. ABCB1 3435TT carriers presented lower trough (R,S)-methadone plasma levels (2.7 and 3.4 ng/mL . mg for 3435TT and 3435CC carriers, respectively; P = .01). The CYP1A2, CYP2C9, CYP2C19, CYP3A5, and UGT2B7 genotypes did not influence methadone plasma levels. Only CYP2B6 displayed a stereoselectivity in its activity. CONCLUSION: In vivo, CYP3A4 and CYP2B6 are the major CYP isoforms involved in methadone metabolism, with CYP2D6 contributing to a minor extent. ABCB1 genetic polymorphisms also contribute slightly to the interindividual variability of methadone kinetics. The genetic polymorphisms of these 4 proteins had no influence on the response to treatment and only a small influence on the dose requirement of methadone.

[New Drugs: Ectasy and Gamma-Hydroxy-Butyrate (GHB)]. / Nuevas drogas: Extasis y Gamma-Hidroxi-Butirato (GHB).

For several years the "raves" and "tecno" parties are accompanied of a growing consumption of such substances as Ecstasy and Gamma-Hidroxi-Butirato (GHB). In this article, their authors describe the secondary and toxic effects of those drugs. These data should alert about the risk of considering this new way of substance abuse as a banal fact.

Nuevas drogas: Extasis y Gamma-Hidroxi-Butirato (GHB) / [New Drugs: Ectasy and Gamma-Hydroxy-Butyrate (GHB)]

For several years the [quot ]raves[quot ] and [quot ]tecno[quot ] parties are accompanied of a growing consumption of such substances as Ecstasy and Gamma-Hidroxi-Butirato (GHB). In this article, their authors describe the secondary and toxic effects of those drugs. These data should alert about the risk of considering this new way of substance abuse as a banal fact.

Nuevas drogas: Extasis y Gamma-Hidroxi-Butirato (GHB). / [New Drugs: Ectasy and Gamma-Hydroxy-Butyrate (GHB)]

For several years the [quot ]raves[quot ] and [quot ]tecno[quot ] parties are accompanied of a growing consumption of such substances as Ecstasy and Gamma-Hidroxi-Butirato (GHB). In this article, their authors describe the secondary and toxic effects of those drugs. These data should alert about the risk of considering this new way of substance abuse as a banal fact.