Attention-deficit/hyperactivity Disorder Medication Use Research Articles

Assessment of Attention Deficits in Adolescent Offspring Exposed to Maternal Type 1 Diabetes.

ObjectiveThe aim of this study was to examine the potential association between intrauterine exposure to maternal diabetes and attention deficits in the offspring.Research design and methodsAdolescent offspring of a prospectively followed cohort of women with type 1 diabetes (n = 269) and a control group from the background population (n = 293) participated in a follow-up assessment in 2012–2013. We used scores from Conners Continuous Performance Test II to assess attention and based on a principal component analysis we evaluated scores on five different attention factors: focused attention, vigilance, hyperactivity/impulsivity, sustained attention and response style.ResultsA higher frequency of the exposed offspring had a parent/self-reported use of Attention Deficit Hyperactivity Disorder (ADHD) medication compared to the control group (2.2% vs. 0.0%, p = 0.01). Clinical significant differences between adolescents exposed to maternal diabetes and unexposed controls were not found in either single scores on Conners Continuous Performance Test or on any of the five attention factors identified.ConclusionsExposure to maternal type 1 diabetes did not seem to increase the risk of attention deficits in the adolescent offspring. However, a higher self-reported use of ADHD medication in the exposed group could suggest a difference in attention not revealed by the applied test.

Organisation of services for managing ADHD.

There is considerable variation in practice, both between and with different countries in the management of attention deficit hyperactivity disorder (ADHD). Whilst there is no one optimal model of service organisation there are general principles of care that can be introduced to reduce this variability. There are frequent debates and discussions about which professional group is best placed to manage ADHD at different points in the life cycle. Who delivers care is however less important than ensuring that training schemes provide adequate exposure, training and experience to both the core and non-core skills required to provide a comprehensive package of care. Most evidence-based guidelines recommend a multi-modal, multi-professional and multi-agency approach. Many also promote the use of both stepped care and shared care approaches for the management of ADHD. As most of those with ADHD continue to have ADHD-related problems into adulthood, it is important to consider how best to transition care into adulthood and think about who should deliver care to adults with ADHD. Young people with ADHD should generally be transferred to adult mental health services if they continue to have significant symptoms of ADHD or other coexisting conditions that require treatment. Unfortunately services for adults with ADHD remain relatively scarce across much of the world and some adult psychiatrists remain unsure of the diagnosis and uncertain about the appropriate use of ADHD medications in adults, but there is a strong case for increased services for adults. ADHD is on the one hand easy to treat; it is much more difficult to treat well. Although optimised care for ADHD requires routine measurement of outcomes, this often does not happen in routine clinical practice. Focusing on optimising symptoms and minimising adverse effects can significantly improve both short- and long-term outcomes.

Attention-deficit hyperactivity disorder medication use: factors involved in prescribing, safety aspects and outcomes

While treatment of patients with attention-deficit hyperactivity disorder (ADHD) is based on a multimodal approach that combines medication with specific psychological interventions, pharmacotherapy alone is generally considered an essential and cost-effective element. This paper aims to comprehensively and critically review factors involved in prescribing and medication use in individuals diagnosed with ADHD, focusing on the difficulties facing patients with ADHD seeking treatment, as well as the safety and tolerability aspects of ADHD pharmacotherapies, with particular attention on the cardiovascular adverse events and the potential risk of misuse or diversion of ADHD medications. A comprehensive and systematic literature search of PubMed/MEDLINE database was conducted to identify studies published in peer-reviewed journals until 1 August 2016. Children, adolescents and adults often encounter significant difficulties in the process of accessing specialist assessment and treatment for ADHD as a consequence of disparities in service organization and available treatment provision. Despite the well-established efficacy and overall safety profile, ADHD medications are not exempt from adverse events. The cardiovascular safety of pharmacotherapies used for treating individuals with ADHD has raised particular concerns; however there is little evidence of serious cardiovascular adverse events, including no serious corrected QT (QTc) abnormalities associated with stimulants, atomoxetine or α2-adrenergic receptor agonists. Although the abuse of prescription stimulant drugs, particularly, short-acting stimulants is a prevalent and growing problem, nonmedical use of prescription stimulants within the clinical context is very limited. In addition, nonstimulant ADHD medications lack any reinforcing effects and consequently any abuse potential.

Attention deficit hyperactivity disorder medications in children with heart disease

Attention deficit hyperactivity disorder (ADHD) is quite common in the general pediatric population, Its incidence is thought to be even higher in the population of patients with congenital heart disease, especially in those patients with complex disease and who have had cardiac surgical interventions early in life. There has been controversy as to the safety of ADHD medications, especially in the latter population of patients. This compendium is meant to review the effects of the ADHD medications and the safety of these medications in patients with either known or undiagnosed congenital heart disease. The concern with regard to the use of ADHD medications has been as a result of the reports of sudden unexpected deaths among patients taking stimulant drugs for ADHD. Therefore, the question of whether or not stimulant drugs increase the risk of adverse cardiovascular events has led to a discussion of the appropriate use of these drugs in patients with known cardiovascular disease, as well as a discussion as to the appropriate evaluation in order to identify undiagnosed 'at-risk' patients with congenital heart disease or arrhythmias. This article will review and amplify these discussions, as well as the conclusions that have come forth as a result of these discussions. Currently available data suggest that there is no evidence for serious adverse cardiovascular complications in children with known cardiovascular diseases including patients of congenital heart disease who are treated with stimulant medications. Despite this, if the patient does have known cardiac disease, or if the history and physical examination is suggestive of cardiac disease, it is suggested that consultation/evaluation with a pediatric cardiologist occur. It is extremely unlikely that stimulant medications would be contraindicated in almost any condition that falls under this category. However, a few specific cardiac conditions might tailor the choice of the specific ADHD medication. Therefore the coordination of care between the primary care physician, the ADHD medication-prescribing physician, and the pediatric cardiologist may be very important in this circumstance.

Attention-deficit hyperactivity disorder comorbidity and antidepressant resistance among patients with major depression: A nationwide longitudinal study

The comorbidity between attention deficit hyperactivity disorder (ADHD) and major depression is common. However, the influence of ADHD comorbidity in the response or resistance to antidepressants remains unknown among patients with major depression. 1891 patients with major depression and ADHD and 1891 age-/sex-matched patients with major depression only were enrolled and followed for 1 year in our study. Use of antidepressants and ADHD medications during 1-year follow-up period were assessed. Antidepressant resistance was defined as treatment failure in two or more than two different antidepressants for adequate treatment dose and duration. Patients with major depression and ADHD had an increased risk of treatment resistance to antidepressants (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.63–3.32) compared with patients with major depression only after adjusting for demographic characteristics and other psychiatric comorbidities. Regular treatment for ADHD would reduce this risk (OR: 1.76, 95% CI: 0.72–4.27). Anxiety (OR: 3.15, 95% CI: 2.24–4.44) and substance use (OR: 2.45, 95% CI: 1.16–5.17) disorders were also associated with an elevated likelihood of resistance to antidepressants during the follow-up. Patients who had dual diagnoses of major depression and ADHD were more likely to have treatment resistance to antidepressants compared with patients with major depression only. Prompt and regular treatment for ADHD would reduce this risk.

Use of psychotropic drugs in patients with autism spectrum disorders: a systematic review.

The objective of this review was to examine prevalence and patterns of psychopharmacotherapy in individuals with autism spectrum disorder (ASD). A systematic literature search in PubMed, CINAHL, and PsycINFO was performed, including articles published up to November 18, 2015. A total of 47 studies (data collection: 1976-2012), encompassing >300000 individuals with ASD, were included. The prevalence of psychopharmacotherapy ranged from 2.7% to 80% (median (overall): 45.7%; median (children): 41.9%; median (adults): 61.5%), with psychotropic polypharmacy occurring in 5.4-54% (median: 23.0%). Regarding drug classes, antipsychotics were most frequently used, followed by attention-deficit/hyperactivity disorder (ADHD) medication and antidepressants. Both older age and psychiatric comorbidity were associated with higher prevalences of psychopharmacotherapy and psychotropic polypharmacy. There were no time trends in psychopharmacotherapy prevalence observable. Despite a lack of pharmacological treatment options for ASD core symptoms, the prevalence of psychopharmacotherapy and polypharmacy in ASD patients is considerable, which is probably due to the treatment of non-core ASD symptoms and psychiatric comorbidities. While there is some evidence for the use of antipsychotics and ADHD medication for these indications, the use of antidepressants should be limited to selected cases.

Racial and Ethnic Disparities in ADHD Diagnosis and Treatment.

We examined racial/ethnic disparities in attention-deficit/hyperactivity disorder (ADHD) diagnosis and medication use and determined whether medication disparities were more likely due to underdiagnosis or undertreatment of African-American and Latino children, or overdiagnosis or overtreatment of white children. We used a population-based, multisite sample of 4297 children and parents surveyed over 3 waves (fifth, seventh, and 10th grades). Multivariate logistic regression examined disparities in parent-reported ADHD diagnosis and medication use in the following analyses: (1) using the total sample; (2) limited to children with an ADHD diagnosis or symptoms; and (3) limited to children without a diagnosis or symptoms. Across all waves, African-American and Latino children, compared with white children, had lower odds of having an ADHD diagnosis and of taking ADHD medication, controlling for sociodemographics, ADHD symptoms, and other potential comorbid mental health symptoms. Among children with an ADHD diagnosis or symptoms, African-American children had lower odds of medication use at fifth, seventh, and 10th grades, and Latino children had lower odds at fifth and 10th grades. Among children who had neither ADHD symptoms nor ADHD diagnosis by fifth grade (and thus would not likely meet ADHD diagnostic criteria at any age), medication use did not vary by race/ethnicity in adjusted analysis. Racial/ethnic disparities in parent-reported medication use for ADHD are robust, persisting from fifth grade to 10th grade. These findings suggest that disparities may be more likely related to underdiagnosis and undertreatment of African-American and Latino children as opposed to overdiagnosis or overtreatment of white children.

Association between medication prescription for atopic diseases and attention-deficit/hyperactivity disorder

BackgroundData on the association between atopic diseases and attention-deficit/hyperactivity disorder (ADHD) have been inconclusive. ObjectiveTo assess whether children with drug-treated ADHD are more likely to receive treatment for asthma, allergic rhinitis, or eczema before the start of ADHD medication use compared with controls and to examine the effect of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. MethodsWe conducted a retrospective nested case-control study among children (6-12 years of age) using the Groningen University prescription database. Cases were defined as children with at least 2 prescriptions of methylphenidate within 12 months. For each case, 4 controls were matched on age, sex, and regional area code. Parental prescription data were linked to cases and controls to assess the influence of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. ResultsWe identified 4257 cases and 17,028 matched controls. Drug treatment for asthma, allergic rhinitis, and eczema was more common in cases than controls (adjusted odds ratios [aORs], 1.4 [95% confidence interval (CI), 1.3-1.6], 1.4 [95% CI, 1.1-1.8], and 1.3 [95% CI, 1.1-1.5], respectively). Medication for allergic rhinitis and asthma among parents was associated with ADHD treatment in their children (aORs, 1.3 [95% CI, 1.1-1.5] and 1.2 [95% CI, 1.1-1.3], respectively). ConclusionThis study provides further evidence to support the hypothesis that atopic diseases are associated with ADHD. The parental-offspring association suggests a possible genetic and/or environmental component.

Is attention deficit/hyperactivity disorder among men associated with initiation or escalation of substance use at 15-month follow-up? A longitudinal study involving young Swiss men.

Background and AimsYoung adults with attention deficit/hyperactivity disorder (ADHD) show higher substance use disorder (SUD) prevalence relative to non‐ADHD controls; few longitudinal studies have examined the course of substance use with reference to conduct disorder (CD). We compared initiation and escalation of substance use at 15‐month follow‐up in men screened positive or negative for ADHD (ADHD+ versus ADHD–), controlling for CD presence in early adolescence.DesignParticipants were recruited during August 2010 and November 2011 from the census of all young men who have to pass mandatory army conscription from three of six Swiss Army recruitment centres. A two‐wave data collection was performed via questionnaires at baseline and 15‐month follow‐up as a part of the longitudinal Cohort Study on Substance Use Risk Factors.SettingRecruitment centres in Lausanne, Windisch and Mels, responsible for 21 cantons in German‐ and French‐speaking areas of Switzerland.ParticipantsConsecutive sample of 5103 male Swiss Army conscripts who provided informed consent and responded to questionnaires at baseline and 15‐month follow‐up. Their mean age was 20.0 (standard deviation = 1.21) years at baseline.MeasurementsADHD and CD were assessed using the adult ADHD Self‐Report Scale and the MINI International Neuropsychiatric Interview Plus, respectively, at baseline, and substance use was measured via self‐administered substance use questionnaires at baseline and follow‐up.FindingsCompared with the ADHD– group, the ADHD+ group (n = 215, 4.2%) showed heavier baseline substance use and increased likelihood of alcohol (χ2 = 53.96; P < 0.001), tobacco (χ2 = 21.73; P < 0.001) and cannabis use disorders (χ2 = 48.43; P < 0.001). The extent of alcohol, tobacco and cannabis use in the two groups remained stable from baseline to follow‐up (no escalation). The ADHD+ group was more likely to initiate substance use compared with the ADHD– group (higher initiation rates), particularly with amphetamines [odds ratio (OR) = 3.81; 95% confidence interval (CI) = 2.20–6.60; P < 0.001] and non‐medical use of ADHD medication (OR = 4.45; 95% CI = 2.06–9.60; P < 0.001). CD was associated with initiation of substance use but did not mediate the associations between ADHD and substance use, revealing that the impact of ADHD on substance use was independent of CD.ConclusionsFor men in their early 20s, attention deficit/hyperactivity disorder is a risk factor for continued heavier but not escalating use of alcohol, tobacco and cannabis when already consuming these substances, compared with young men with no ADHD. It is also a risk factor for initiating the use of cannabis, stimulants, hallucinogens and sedatives, independent of conduct disorder in early adolescence.

Effects Of Attention-Deficit/Hyperactivity Disorder Medications On Resistance-Exercise-Induced Hypoalgesia, Perceived Exertion, Heart Rate, And Blood Lactate

PURPOSE:An increase in prescribed stimulant medication for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) has led to treatment misuse as a result of the ability of these medications to improve concentration and decrease fatigue. Although they provide cognitive benefits, the effects of stimulant treatment for ADHD during physical activity are fairly unknown. The primary goal of this study was to investigate the effects of ADHD medications on resistance exercise-induced pain perception, perceived exertion, heart rate, and blood lactate concentrations. METHODS:Thirty college-age students (10 no ADHD diagnosis, 10 ADHD diagnosis, and 10 ADHD diagnosis with medications) completed 2 sessions: 1) a maximal testing session and 2) an experimental session consisting of 3 consecutive dynamic resistance exercise circuits. Each circuit was comprised of 12 repetitions of 9 resistance exercises at 60% of 1-repetition maximum using a 1:1 work to rest ratio. Pain and blood lactate concentrations were measured pre- and post-exercise using a pressure algometer and lactate meter, respectively. Heart rate and perceived exertion were measured during the exercise bout. RESULTS:Participants displayed exercise-induced hypoalgesia ([INCREMENT]17.8% ± 5.2, p = 0.002) 1-min post-exercise, accompanied by an increase in blood lactate (12.47 ± 0.66mM, p = 0.000). Moreover, participants displayed significant elevations in heart rate (p = 0.000) and perceived exertion (p = 0.000) for the duration of the exercise bout. These findings for pain tolerance, lactate, heart rate, and perceived exertion were similar regardless of condition (no ADHD diagnosis vs. ADHD without medications vs. ADHD with medications). CONCLUSIONS:Dynamic resistance exercise produces increases in pain tolerance, perceived exertion, heart rate, and blood lactate. The effects of resistance exercise are not altered by ADHD diagnosis or psychostimulant medication use for ADHD. These findings are intriguing given the known ergogenic and analgesic effects of caffeine, a less potent stimulant.

Use of acetaminophen (paracetamol) during pregnancy and the risk of attention-deficit/hyperactivity disorder in the offspring.

Prenatal exposure to acetaminophen may result in compromised neurodevelopment through inflammatory and immunologic mechanisms, through predisposition to oxidative stress, and through endocrine, endogenous cannabinoid, and other mechanisms. Several small and large prospective studies have found an association between gestational acetaminophen exposure and attention-deficit/hyperactivity disorder (ADHD)-like behaviors, use of ADHD medication, and ADHD diagnoses in offspring during childhood; the only negative study was a small investigation that examined only one aspect of attention as an outcome. Creditably, most of the studies adjusted analyses for many (but not all) confounds associated with ADHD risk. Importantly, one pivotal study also adjusted for pain, infection, inflammation, and fever to reduce confounding by indication; this study found a dose-dependent risk. In the light of the finding of a single study that infection and fever during pregnancy by themselves do not raise the ADHD risk, it appears possible that the use of acetaminophen during pregnancy is itself responsible for the increased risk of ADHD. This suggests that acetaminophen may not be as safe in pregnancy as is widely believed. However, since fever during pregnancy may itself be associated with adverse gestational outcomes, given the present level of uncertainty about the ADHD risk with acetaminophen, it is suggested that, until more data are available, the use of acetaminophen in pregnancy should not be denied in situations in which the need for the drug is clear.

Effective treatment of attention-deficit hyperactivity disorder also helps control symptoms of comorbid oppositional defiant disorder

The most common comorbidity of attention-deficit hyperactivity disorder (ADHD) is oppositional defiant disorder (ODD), and children with this combination have increased symptom severity and impairment. Treatment strategies include education, behavioural management therapy approaches, providing school and academic supports, and the use of stimulant or non-stimulant ADHD medications, depending on symptom severity and consideration of child and parental wishes. Effective ADHD treatment is also helpful for comorbid ODD symptoms.

Impact of a Step Therapy for Guanfacine Extended-Release on Medication Utilization and Health Care Expenditures Among Individuals Receiving Treatment for ADHD.

While step therapy (ST) policies are generally effective at reducing cost through the managed utilization of targeted medications, the clinical implications of ST policies are not clear and may vary across therapeutic areas. Guanfacine extended-release (GXR) is approved by the FDA for the treatment of attention-deficit/hyperactivity disorder (ADHD) as both monotherapy and adjunctive to stimulant treatment. At the introduction of GXR to the market, Humana implemented an ST policy on GXR requiring the documentation of previous treatment, intolerance, or contraindication to generic clonidine or guanfacine. To examine the impact of a GXR ST coverage determination (i.e., approved vs. denied) on medication utilization and health care costs among members of a commercial health plan with an ST policy for GXR. This study was a retrospective cohort study of administrative claims data. Humana commercial members prescribed GXR who had an ST coverage determination review were identified. All members included in this analysis were required to be aged 6-17 years, have a diagnosis of ADHD or be receiving stimulant medication, have an ST coverage determination (index event) between September 1, 2009, and May 30, 2012, and have 6 months of pre- and post-index continuous enrollment. Members were assigned to either the approved or denied group based on the outcome of the ST coverage determination. Medical and pharmacy claims data were used to measure baseline demographic and clinical characteristics and to measure medication utilization and health care costs. Outcomes assessed during follow-up included ADHD medication use, proportion of days covered (PDC) with any ADHD medication treatment, time to first observed post-index ADHD treatment, and all-cause and mental health (MH)-related health care costs. Administrative costs associated with the coverage determination process were also estimated. Bivariate and multivariable adjusted analyses were conducted to compare medication utilization and health care costs between the approved and denied groups. A total of 642 members were included in the analysis (denied group n = 395 [61.5%], approved group n = 247 [38.5%]). The approved and denied groups were similar in terms of baseline demographics, provider characteristics, and baseline MH diagnoses, with the exception of anxiety disorders being more prevalent in the approved group compared with the denied group (18.2% vs. 10.6%, P = 0.006). A denied GXR coverage determination was associated with a greater percentage of members receiving no ADHD treatment post-index (13.9% vs. 3.2%, P less than 0.001), greater mean [SD] number of days between index and first observed post-index ADHD medication claim (44.5 [59.6] vs. 17.6 [33.4], P less than 0.001), and lower mean [SD] PDC with any ADHD medication post-index (0.59 [0.33] vs. 0.75 [0.26], P less than 0.001). These findings remained statistically significant in multivariable regression models. Unadjusted pre-index median total health care costs and MH-related costs were greater among the approved group compared with the denied group (total health care: $1,582 vs. $1,465, P = 0.033; MH-related: $993 vs. $981, P = 0.020). Likewise, post-index median total health care and MH-related costs were greater among the approved group compared with the denied group (total: $2,056 vs. $1,420, P less than 0.001; MH-related: $1,543 vs. $946, P less than 0.001). After adjustment for potentially confounding covariates including pre-index costs, there were no statistically significant differences between the approved and denied groups in all-cause total health care (P = 0.393) or MH-related health care costs (P = 0.054). The current study found that GXR coverage denial was associated with lower rate of ADHD medication utilization, greater delay in receiving ADHD medication, and lower PDC with ADHD medication. There were no differences observed between the approved and denied group in terms of all-cause total health care or MH-related total health care costs after controlling for potentially confounding variables. Prior to implementation in the ADHD therapeutic area and others, payers should consider the potentially unintended consequences of ST policies, including delay in treatment and undertreatment.

Real-World Dosing Patterns of Atomoxetine in Adults with Attention-Deficit/Hyperactivity Disorder.

SummaryAimsThe aim was to investigate the dosing patterns of atomoxetine monotherapy in adult patients with attention‐deficit/hyperactivity disorder (ADHD) in a retrospective analysis.MethodsAdult (≥18 years) patients with ADHD newly initiated on atomoxetine with ≥1 outpatient pharmacy claim for atomoxetine between January 2006 and December 2011 were selected from the Truven Health MarketScan® Commercial database. After a 30‐day titration period, dosing patterns of atomoxetine monotherapy were analyzed in the 12 months following initiation. In addition, patient demographic and clinical characteristics were compared to identify characteristics associated with suboptimal versus recommended dosing.ResultsOf the 12,412 adult patients with ADHD newly initiated on atomoxetine, 4548 (36.6%) were suboptimally dosed, whereas 3323 (26.7%) were treated at recommended dose. Overall, study patients were treated at a mean (standard deviation [SD]) dose of 68.5 (44.9) mg/day. The suboptimal dosing cohort included significantly more females (54% vs. 44%, P < 0.001) and had fewer patients with pre‐index use of other ADHD medications (17% vs. 20%, P < 0.001) compared with the recommended dosing cohort.ConclusionsAdult patients with ADHD receiving atomoxetine therapy in a real‐world setting are often dosed suboptimally. Increasing the awareness on optimal dosing strategy among clinicians and patients is warranted to maximize the therapeutic benefits of atomoxetine among adult patients with ADHD.

Geographic analysis of the variation in the incidence of ADHD in a country with free access to healthcare: a Danish cohort study.

BackgroundThe prevalence of citizens diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) has risen dramatically over the past decades in many countries, however, with large variations. Countries such as Denmark with centrally organized well fare systems, free access to health services and individual tracking based on unique personal identification may in particular contribute to our understanding of the reasons for this increase. Based on Danish registers we aimed to examine the geographical patterns of the distribution of ADHD diagnosis and medication use and explore the association with access to diagnostic services, diagnostic culture, neighbourhood socioeconomic status and municipal spending on health care for children.MethodsWe combined information on registered diagnosis of ICD-10 Hyperkinetic Disorder and ADHD medication use in a Danish register-based cohort of children born between 1990 and 2000. We mapped incidence proportions of diagnoses and medication use within the 98 Danish Municipalities. Global and local clustering of ADHD was identified using spatial analysis. Information on contextual factors in the municipalities was obtained from national registers. The associations between the incidence of ADHD and contextual factors were analysed using Bayesian spatial regression models.ResultsWe found a considerable variation in the incidence of ADHD across the municipalities. Significant clustering of both high and low incidence of ADHD was identified and mapped using the local Moran’s I. Clustering of low incidence of diagnosis and medication use was observed in less populated areas with limited diagnostic resources and in contrast clustering of high incidence in densely populated areas and greater diagnostic resources. When considering the spatial autocorrelation between neighbouring municipalities, no significant associations were found between ADHD and access to diagnostic services, different diagnostic culture, socioeconomic status at municipality level or the municipal spending on health care for children.ConclusionsA large geographical variation of ADHD in the municipalities was observed despite tax-financed and free access to healthcare. Although not statistically significant, results indicate that accessibility to diagnostic resources might explain some of the variation in ADHD incidence. In contrast to US studies the observed variation was not statistically associated to contextual factors in terms of SES, municipal spending on health care for children or differences in diagnostic practices.

Med Check

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessMed CheckVabren WattsVabren WattsSearch for more papers by this authorPublished Online:6 Aug 2015https://doi.org/10.1176/appi.pn.2015.8a12Ketamine Effects Sustained Over Two MonthsAnother small-scale clinical trial for ketamine has catapulted the drug back into headlines of some major news outlets, suggesting that the effectiveness of the NMDA-receptor antagonist can be sustained with help from other pharmacoagents. Researchers from Columbia University administered various doses of lurasidone, olanzapine/fluoxetine, or quetiapine to eight patients with treatment-resistant bipolar depression for one month before infusing the patients with a one-time dose of ketamine (0.5 mg/kg) for 60 minutes, immediately followed by 300 to 1,000 mg daily doses of the tuberculosis drug D-cyclosporine, another NMDA antagonist, for eight weeks.The researchers observed a 50 percent reduction in depression and a 75 percent reduction in suicidality among participants over one to two weeks, which is not unusual when ketamine is administered alone or with FDA-approved antipsychotics for bipolar depression. What was unique, the researchers noted, was that these effects lasted up to two months in the presence of D-cyclosporine. While the authors of the study noted more studies are needed to assess D-cycloserine’s independent efficacy and safety in bipolar depression, the study received much praise from NeuroRX, a small biotech company that is developing a ketamine/lurasidone/D-cyclosporine combo treatment for bipolar depression. The company was not involved with this study.According to a statement released by NeuroRX, “This is the first clinical report showing that the ketamine effect can potentially be sustained for two months with additional agents.” Kantrowitz J, Halberstam B, Gangwisch J. Single-Dose Ketamine Followed by Daily D-Cycloserine in Treatment-Resistant Bipolar Depression. J Clin Psychiatry. 2015. 76(6):737-8.Pristiq Fails in Pediatric TrialsPfizer’s Pristiq ER was recently found to be no more effective in children than placebo, according to the company. This selective serotonin and norepinephrine reuptake inhibitor (SNRI) received approval by the FDA in 2008 for the treatment of major depressive disorder in adults.The phase 3 trial, which involved 340 youth aged 7 to 17 with major depressive disorder, was the first of four phase 3 pediatric trials being conducted as part of an FDA postmarketing commitment under the Pediatric Research Equity Act, which requires pharmaceutical companies to conduct pediatric studies with recently approved drugs for the same use for which those drugs were approved in adults.Lundbeck and Otsuku Set to Launch New AntipsychoticIn July, the FDA approved the Lundbeck and Otsuku co-developed drug Rexulti (brexpiprazole), which is intended to treat schizophrenia and major depressive disorder. The drug is a dopamine D2 and serotonin 5-HT1A partial agonist.The effectiveness of the new compound was shown in a multisite international study published April 17 in AJP in Advance. In the study, patients administered 2 mg and 4 mg of brexpiprazole for six weeks had significantly lower scores on the Positive and Negative Syndrome Scale than those who took placebo, with no clinically significant changes in baseline lipid and glucose levels and extrapyramidal symptom ratings (Psychiatric News, May 15, 2015).In a press statement, Lundbeck noted that in most trials concerning Rexulti, more than 90 percent of participants completed treatment protocols, making the drug one of the “best-in-class” for tolerability. The company expects that the drug could be on the market as soon as the end of this month.Adults Take More ADHD Meds Than Children Children are no longer the prime market for medicines used to treat attention-deficit/hyperactivity disorder (ADHD) in the United States, according to a recent report by Shire Pharmaceuticals. According to Shire, which manufactures the top-selling ADHD medication Vyvanse (lisdexamfetamine), compiled data from a national database on prescription drugs revealed that 53 percent of prescriptions for ADHD medications in 2014 (63 million prescriptions) were for adults, up from 39 percent in 2007. Children aged 6 to 17 accounted for 47 percent of such prescriptions in 2014, down from 61 percent in 2007.A report in Bloomberg suggests the market shift may be due to growing evidence that the disorder can persist into adulthood and findings that show that more parents of children with ADHD are being diagnosed with the condition amid the growing awareness that ADHD can be inherited.During a conference call with analysts, Shire’s CEO Flemming Ornskov said that the company “has shifted more efforts into the adult ADHD market” and will be directing sales representatives to spend more time telling physicians about studies concerning adult use of ADHD medications. ■ ISSUES NewArchived

Long-QT Syndrome and Therapy for Attention Deficit/Hyperactivity Disorder.

Stimulants are the mainstay therapy for attention deficit/hyperactivity disorder (ADHD) and are associated with adrenergic side effects. There are limited data on the clinical course of patients treated for ADHD who have long-QT syndrome (LQTS), for which β-blockade is the goal of therapy. LQTS patients from the Rochester-based LQTS Registry (open-enrollment between 1979 and 2003; follow-up from 1979 to present) treated with stimulant or nonstimulant ADHD medications (n = 48) were compared to a 2:1 age-, gender-, and QTc-duration matched LQTS control group not exposed to ADHD medications (n = 96). Kaplan-Meier and Cox proportional hazards regression analyses were used to evaluate risk of cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) in LQTS patients treated with ADHD medications. During a mean follow-up of 7.9 ± 5.4 years after initiation of ADHD medication at a mean age 10.7 ±7.3 years, there was a 62% cumulative probability of cardiac events in the ADHD treatment group compared to 28% in the matched LQTS control group (P < 0.001). Time-dependent use of ADHD medication was associated with an increased risk for cardiac events (HR = 3.07; P = 0.03) in the multivariate Cox model adjusted for time-dependent β-blocker use and prior cardiac events. Subgroup gender analyses showed that time-dependent ADHD medication was associated with an increased risk in male LQTS patients (HR = 6.80, P = 0.04). LQTS patients treated with ADHD medications have increased risk for cardiac events, particularly syncope, and this risk is augmented in males. The findings highlight the importance of heightened surveillance for LQTS patients on ADHD medications.

Attention Deficit Hyperactivity Disorder Medication Use Among Teens and Young Adults

PurposeThe purpose of this study was to determine rates of stimulant/atomoxetine use among teens (aged 12–17 years) and young adults (aged 18–23 years) and to investigate associations in medication use before and after the transition from teen to young adult. MethodsRepeated cross-sectional analyses using the nationally representative Medical Expenditure Panel Survey. The sample included all teens and young adults between 2003 and 2012. Within this group, a staggered sample of individuals between 2006 and 2012 born during a 5-year range was used to minimize false positive findings due to temporal trends. The primary outcome was attention deficit hyperactivity disorder (ADHD) medication use (two or more prescriptions and ≥60 tablets). A multivariable logistic regression was utilized to determine associations between ADHD medication use and race/ethnicity and other sociodemographic factors. ResultsA total of 62,699 individuals were included between 2003 and 2012. Rates of ADHD medication use increased for both teens (4.2%–6.0%) and young adults (1.2%–2.6%) between 2003–2004 and 2011–2012. In adjusted analysis, blacks, Hispanics, and Asians had lower rates of use compared with whites. The decrease in use among young adults was more pronounced among blacks compared with whites. A usual source of care and health insurance were less common among young adults, and both were associated with ADHD medication use. ConclusionsAlthough there has been an increase in the use of ADHD medications in both teens and young adults, we found a drop-off in levels of ADHD treatment among young adults when compared with teens. A portion of this decrease appears to be related to race/ethnicity, usual source of care, and health insurance status.

Treatment of Childhood Oppositional Defiant Disorder

Oppositional defiant disorder (ODD) is a common behavioral disorder of childhood which can be described as a learned pattern of behavior reinforced by caregivers’ responses. Behavioral modification for ODD, particularly in preschool and school-aged children, should primarily focus on teaching caregivers to reinforce positive behaviors, discourage negative behaviors, and ultimately interrupt the cycle of argumentativeness and deliberate attention-seeking behavior. Unfortunately, children who are referred for behavioral therapy for ODD often do not receive evidence-based treatments that target the root cause of the disorder. There is some role for the use of psychopharmacology in the treatment of ODD, though primarily in the treatment of underlying and comorbid disorders. The core symptoms of ODD are not amenable to pharmacotherapy, and behavioral modification is the mainstay of intervention. Attention-deficit hyperactivity disorder (ADHD) frequently occurs with ODD. Poor impulse control is a core feature of ADHD, and appropriate use of stimulant and/or non-stimulant ADHD medications can help children with ODD make better behavioral choices and be more successful with behavior modification programs. There is some evidence for the effectiveness of atypical antipsychotics in disruptive behavior disorders (DBDs), but the target symptoms of explosive and aggressive behaviors are seen only in children with more severe ODD who progress to conduct disorder (CD). Pediatric providers should understand the evidence-based behavioral interventions and targeted psychiatric medications that will achieve the best outcomes for children with ODD.

Adverse pregnancy outcomes after exposure to methylphenidate or atomoxetine during pregnancy.

ObjectiveTo determine if prenatal exposure to methylphenidate (MPH) or atomoxetine (ATX) increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD).Materials and methodsThis was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers.ResultsWe identified 989,932 pregnancies, in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation) (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03–2.36). The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11–2.20). The aRR of Apgar scores <10 was increased among exposed women (aRR 2.06, 95% CI 1.11–3.82) but not among unexposed women with ADHD (aRR 0.99, 95% CI 0.48–2.05).ConclusionMPH/ATX was associated with a higher risk of SA, but our study indicated that it may at least partly be explained by confounding by indication. Treatment with MPH/ATX was however associated with low Apgar scores <10, an association not found among women with ADHD who did not use MPH/ATX.