The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition that globally affects an average of around 5% of children and is associated with several adverse life outcomes. Comorbidity with autism spectrum disorder (ASD) is highly prevalent. Pharmacological treatment for ADHD symptoms has been shown to be effective. However, the prevailing perception is that children with ADHD and concomitant ASD symptoms report poorer efficacy and more side effects. This has been supported by studies on this population, but prospective studies directly comparing children with ADHD and different levels of ASD symptoms are lacking. We aimed to assess if children with ADHD and concomitant ASD symptoms differ regarding effects and side-effects of pharmacological ADHD treatment compared to children with ADHD without ASD traits. This is to our knowledge the second study to directly compare the effect of ADHD medication between ADHD patients with different levels of ASD symptoms. METHODS: In a non-randomized, observational, prospective cohort study, 323 patients aged 6 to 17 years who were diagnosed with ADHD and starting pharmacological treatment were divided into two groups: one with high level of ASD symptoms (ASD group, N=71) and one with low level of ASD symptoms (non-ASD group, N = 252). Treatment outcome was measured as ADHD symptoms, and evaluated using the Swanson, Nolan and Pelham Teacher and Parent ADHD rating scale-version IV (SNAP-IV). Side-effects were evaluated using the Pediatric Side Effects Checklist (P-SEC), at 3 months follow-up. RESULTS: From baseline to 3 months, there was no significant difference in neither treatment effect nor number of clinically significant adverse events experienced between the ASD group and the non-ASD group. CONCLUSIONS: Our results did not implicate that ADHD patients with concomitant ASD symptoms have decreased treatment effect of ADHD medication than patients with ADHD without concomitant ASD symptoms. Neither did the results support that ADHD patients with ASD symptoms experienced significantly more side-effects than ADHD patients without ASD symptoms. Although, we did not analyze different medications separately, this is in line with the only previous study directly comparing methylphenidate treatment in children with or without ASD. TRIAL REGISTRATION: NCT02136147 , May 12, 2014.

How does a real-world child psychiatric clinic diagnose and treat attention deficit hyperactivity disorder?

AIM: To investigate child and adolescent psychiatrists' (CAPs) attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) diagnoses and treatments in real-world clinical practice. METHODS: The medical records of 69 ADHD children (mean age = 9.5 years), newly referred to the ADHD clinic, were reviewed for their scores of parent- and teacher-reported Vanderbilt ADHD Diagnostic Rating Scales (VADRSs), CAPs' diagnoses of ADHD and ODD, and CAPs' treatment recommendations. Among 63 ADHD subjects who completed both parent and teacher VADRSs, we examined the agreement of the parent and teacher VADRSs. We also examined the concurrent validity of CAPs' ODD diagnoses against the results from the VADRSs. In addition, we compared CAPs' treatment recommendations against established ADHD and ODD guidelines. RESULTS: Among 63 ADHD subjects, the majority of the subjects (92%) met full ADHD diagnostic criteria at least in one setting (parent or teacher) on the VADRSs. Nearly half of the patients met full ADHD diagnostic criteria in two settings (parent and teacher). Relatively low agreement between the parent and teacher VADRSs were found (95%CI: -0.33 to 0.14). For 29 children who scored positive for ODD on the rating scales, CAPs confirmed the ODD diagnosis in only 12 of these case-positives, which is considered as a fair agreement between CAPs and VADRSs (95%CI: 0.10-0.53). For 27 children with no ODD diagnosis made by either CAP or VADRS, more than half of them were recommended for medication only. In contrast, where CAPs made the diagnosis of ODD, or where the parent or teacher VADRS was positive for ODD, almost all of the patients received recommendations for medication and behavior therapy. CONCLUSION: CAPs' ADHD diagnoses have strong concurrent validity against valid rating scales, but ADHD's most common comorbid condition - ODD - may be under-recognized.

Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine.

This study examines the relationship between blood concentrations of venlafaxine and its active metabolite, O-desmethyl venlafaxine (ODV), and genetic variants of the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human subjects. Trough blood concentrations were measured at steady state in patients treated with venlafaxine extended release in a clinical practice setting. CYP2D6 and CYP2C19 genotypes were converted to activity scores based on known activity levels of the two alleles comprising a genotype. After adjusting for drug dose and gender effects, higher CYP2D6 and CYP2C19 activity scores were significantly associated with lower venlafaxine concentrations (P < 0.001 for each). Only CYP2D6 was associated with the concentration of ODV (P < 0.001), in which genotypes with more active alleles were associated with higher ODV concentrations. The sum of venlafaxine plus ODV concentration showed the same pattern as venlafaxine concentrations with CYP2D6 and CYP2C19 genotypes with higher activity scores being associated with a lower venlafaxine plus ODV concentration (2D6 P = 0.01; 2C19 P < 0.001). Because allelic variants in both CYP2D6 and CYP2C19 influence the total concentration of the active compounds venlafaxine and ODV, both CYP2D6 and CYP2C19 genotypes should be considered when using pharmacogenomic information for venlafaxine dose alterations.