Sleep Quality and Duration in Children That Consume Caffeine: Impact of Dose and Genetic Variation in ADORA2A and CYP1A.

Caffeine is the most consumed drug in the world, and it is commonly used by children. Despite being considered relatively safe, caffeine can have marked effects on sleep. Studies in adults suggest that genetic variants in the adenosine A2A receptor (ADORA2A, rs5751876) and cytochrome P450 1A (CYP1A, rs2472297, rs762551) loci are correlated with caffeine-associated sleep disturbances and caffeine intake (dose), but these associations have not been assessed in children. We examined the independent and interaction effects of daily caffeine dose and candidate variants in ADORA2A and CYP1A on the sleep quality and duration in 6112 children aged 9-10 years who used caffeine and were enrolled in the Adolescent Brain Cognitive Development (ABCD) study. We found that children with higher daily caffeine doses had lower odds of reporting > 9 h of sleep per night (OR = 0.81, 95% CI = 0.74-0.88, and p = 1.2 × 10-6). For every mg/kg/day of caffeine consumed, there was a 19% (95% CI = 12-26%) decrease in the odds of children reporting > 9 h of sleep. However, neither ADORA2A nor CYP1A genetic variants were associated with sleep quality, duration, or caffeine dose. Likewise, genotype by caffeine dose interactions were not detected. Our findings suggest that a daily caffeine dose has a clear negative correlation with sleep duration in children, but this association is not moderated by the ADORA2A or CYP1A genetic variation.

Pharmacogenetic Testing Knowledge and Attitudes among Pediatric Psychiatrists and Pediatricians in Alberta, Canada.

OBJECTIVE: To assess knowledge, attitudes, and barriers as well as ethical, legal and social concerns towards pharmacogenetic (PGx) testing among pediatric psychiatrists and pediatricians in Alberta, Canada. METHOD: An anonymous electronic survey was sent to pediatric psychiatrists (n = 49) and pediatricians (n = 93) in Alberta. RESULTS: A total of 20 surveys were completed (response rate = 14%). Respondents agreed that PGx testing is clinically useful and a majority believed testing had the potential to aid in medication selection, dosing, switching, augmentation, and deprescribing, particularly among children with treatment-resistant conditions. However, most respondents could not identify an appropriate lab to perform testing, did not have the necessary training to interpret PGx results, and did not have access to experts that could assist them in interpreting results. CONCLUSION: The findings suggest additional PGx education and training is required to boost self-efficacy and uptake of PGx testing among pediatric psychiatrists and pediatricians in Alberta, Canada. In addition, local and global efforts to develop clinical practice guidelines, provide clear legal guidance, and ensure equitable access to testing may facilitate the implementation of PGx-informed prescribing.

OBJECTIF: Évaluer les connaissances, les attitudes, et les obstacles ainsi que les préoccupations éthiques, légales et sociales à l'égard des tests pharmacogénétiques (PGx) chez les psychiatres pédiatriques et les pédiatres d'Alberta, Canada. MÉTHODE: Un sondage anonyme électronique a été envoyé à des psychiatres pédiatriques (n = 49) et des pédiatres (n = 93) en Alberta. RÉSULTATS: En tout, 20 sondages ont été remplis (taux de réponse = 14 %). Les répondants convenaient que les tests PGx sont cliniquement utiles et une majorité croyait que les tests avaient le potentiel d'aider à la sélection des médicaments, au dosage, au changement, à l'augmentation et à la déprescription, particulièrement chez les enfants ayant des maladies réfractaires au traitement. Toutefois, la plupart des répondants ne pouvaient pas identifier un laboratoire approprié pour exécuter les tests, n'avaient pas la formation nécessaire pour interpréter les résultats des PGx, et n'avaient pas accès à des experts qui pourraient les aider à interpréter les résultats. CONCLUSION: Les résultats suggèrent qu'il faut plus d'éducation et de formation sur les PGx pour stimuler l'auto-efficacité et l'utilisation des tests PGx chez les psychiatres pédiatriques et les pédiatres de l'Alberta, Canada. En outre, les initiatives locales et mondiales en vue d'élaborer des guides de pratique clinique, d'offrir un guide juridique clair, et d'assurer un accès équitable aux tests peuvent faciliter la mise en œuvre de la prescription éclairée des PGx.

Perspectives on the Clinical Use of Pharmacogenetic Testing in Late-Life Mental Healthcare: A Survey of the American Association of Geriatric Psychiatry Membership.

OBJECTIVE: To assess perspectives on pharmacogenetic (PGx) testing among members of the American Association of Geriatric Psychiatry (AAGP). DESIGN: Cross-sectional survey. PARTICIPANTS: Members of the AAGP. MEASUREMENTS: Anonymous web-based survey consisting of 41 items covering experiences, indications, barriers, facilitators and ethical, legal and social implications for PGx testing. RESULTS: A total of 124 surveys were completed (response rate = 13%). Most respondents (60%) had used PGx testing but an equal proportion (58%) was uncertain about the clinical usefulness of PGx testing in late-life mental health. Despite self-reported confidence in the ability to order and interpret PGx testing, 60% of respondents felt there was not enough clinical evidence for them to use PGx testing in their practice. This was compounded by uncertainties related to their ethical obligation and legal liability when interpreting and using (or not using) PGx testing results. Respondents strongly affirmed that clinical and legal guidelines for PGx testing in older adults are needed and would be helpful. CONCLUSION: The findings suggest additional PGx research and physician education in late-life mental healthcare settings is required to reconcile uncertainties related to the clinical efficacy and ethico-legal aspects of PGx testing as well as address current knowledge barriers to testing uptake. These efforts would be further facilitated by the development of clinical practice guidelines to ensure equitable access to testing and standardized implementation of PGx-informed prescribing in older adults.

Use of antidepressants with pharmacogenetic prescribing guidelines in a 10-year depression cohort of adult primary care patients.

OBJECTIVE: To describe the usage patterns of antidepressants with published CYP2D6- and CYP2C19-based prescribing guidelines among depressed primary care patients and estimate the proportion of patients taking antidepressants not recommended for them based on their CYP2C19 and CYP2D6 genotype-predicted metabolizer status. METHODS: Medication use and pharmacogenetic testing results were collected on 128 primary care patients enrolled in a 10-year depression cohort study. At each 12-month interval, we calculated the proportion of patients that: (1) reported use of one or more of the 13 antidepressant medications (i.e. amitriptyline, citalopram, escitalopram, clomipramine, desipramine, doxepin, fluvoxamine, imipramine, nortriptyline, paroxetine, sertraline, trimipramine, venlafaxine) with published CYP2D6- and CYP2C19-based prescribing guidelines, (2) were taking an antidepressant that was not recommended for them based on their CYP2C19 and CYP2D6 genotype-predicted metabolizer phenotype, and (3) switched medications from the previous 12-month interval. RESULTS: The annual proportion of individuals taking an antidepressant with a CYP2D6- and CYP2C19-based prescribing guidelines ranged from 45 to 84%. The proportion of participants that used an antidepressant that was not recommended for them, based on available CYP2D6 and CYP2C19 metabolizer phenotype, ranged from 18 to 29% and these individuals tended to switch medications more frequently (10%) compared to their counterparts taking medication aligned with their metabolizer phenotype (6%). CONCLUSION: One-quarter of primary care patients used an antidepressant that was not recommended for them based on CYP2D6- and CYP2C19-based prescribing guidelines and switching medications tended to be more common in this group. Studies to determine the impact of CYP2D6 and CYP2C19 genotyping on reducing gene-antidepressant mismatches are warranted.