Background:Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also... Show moreBackground:Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations.Objective:The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience.Method:A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD.Results:After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n= 4), risk of developing SUD (n= 3), screening and diagnosis (n= 7), psychosocial treatment (n= 5), pharmacological treatment (n= 11), and complementary treatments (n= 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion.Conclusion:This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD. Show less
Özgen, H.; Spijkerman, R.; Noack, M.; Holtmann, M.; Schellekens, A.S.A.; Glind, G. van de; ... ; Hendriks, V. 2020
This randomized clinical trial examines whether sildenafil reduces the risk of perinatal mortality or morbidity vs placebo in children of pregnant women with severe early onset fetal growth... Show moreThis randomized clinical trial examines whether sildenafil reduces the risk of perinatal mortality or morbidity vs placebo in children of pregnant women with severe early onset fetal growth restriction.Question Does sildenafil reduce the risk of perinatal mortality or morbidity in children of pregnant women with severe early onset fetal growth restriction? Findings In this randomized clinical trial including 216 pregnant women, perinatal mortality or major morbidity was not statistically different and occurred in the offspring of 60.2% of participants allocated to sildenafil vs 54.2% of those allocated to placebo. Pulmonary hypertension occurred in 18.8% of neonates in the sildenafil group compared with 5.1% of neonates in the placebo group, which was statistically significantly different. Meaning These findings suggest that treatment of severe early onset fetal growth restriction by maternal sildenafil did not reduce the risk of perinatal mortality or major neonatal morbidity, but increased neonatal pulmonary hypertension was observed.Importance Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes. Objective To determine whether sildenafil reduces perinatal mortality or major morbidity. Design, Setting, and Participants This placebo-controlled randomized clinical trial was conducted at 10 tertiary referral centers and 1 general hospital in the Netherlands from January 20, 2015, to July 16, 2018. Participants included pregnant women between 20 and 30 weeks of gestation with severe fetal growth restriction, defined as fetal abdominal circumference below the third percentile or estimated fetal weight below the fifth percentile combined with Dopplers measurements outside reference ranges or a maternal hypertensive disorder. The trial was stopped early owing to safety concerns on July 19, 2018, whereas benefit on the primary outcome was unlikely. Data were analyzed from January 20, 2015, to January 18, 2019. The prespecified primary analysis was an intention-to-treat analysis including all randomized participants. Interventions Participants were randomized to sildenafil, 25 mg, 3 times a day vs placebo. Main Outcomes and Measures The primary outcome was a composite of perinatal mortality or major neonatal morbidity until hospital discharge. Results Out of 360 planned participants, a total of 216 pregnant women were included, with 108 women randomized to sildenafil (median gestational age at randomization, 24 weeks 5 days [interquartile range, 23 weeks 3 days to 25 weeks 5 days]; mean [SD] estimated fetal weight, 458 [160] g) and 108 women randomized to placebo (median gestational age, 25 weeks 0 days [interquartile range, 22 weeks 5 days to 26 weeks 3 days]; mean [SD] estimated fetal weight, 464 [186] g). In July 2018, the trial was halted owing to concerns that sildenafil may cause neonatal pulmonary hypertension, whereas benefit on the primary outcome was unlikely. The primary outcome, perinatal mortality or major neonatal morbidity, occurred in the offspring of 65 participants (60.2%) allocated to sildenafil vs 58 participants (54.2%) allocated to placebo (relative risk, 1.11; 95% CI, 0.88-1.40; P = .38). Pulmonary hypertension, a predefined outcome important for monitoring safety, occurred in 16 neonates (18.8%) in the sildenafil group vs 4 neonates (5.1%) in the placebo group (relative risk, 3.67; 95% CI, 1.28-10.51; P = .008). Conclusions and Relevance These findings suggest that antenatal maternal sildenafil administration for severe early onset fetal growth restriction did not reduce the risk of perinatal mortality or major neonatal morbidity. The results suggest that sildenafil may increase the risk of neonatal pulmonary hypertension. Show less
Aiello, S.; Akrame, S.E.; Ameli, F.; Anassontzis, E.G.; Andre, M.; Androulakis, G.; ... ; Zúñiga, J. 2019
