Attention-deficit/hyperactivity Disorder Pharmacotherapy Research Articles

Lisdexamfetamine Dimesylate: A Review in Paediatric ADHD.

Lisdexamfetamine dimesylate (lisdexamfetamine; Elvanse®; Tyvense®), an orally-active dexamfetamine prodrug, is indicated in the EU for the treatment of attention-deficit hyperactivity disorder (ADHD) in children aged ≥ 6years (including adolescents) when the response to previous methylphenidate (MPH) treatment is clinically inadequate. The original approval of the drug was based on the results of phase III trials in children and adolescents with ADHD who had an inadequate response to previous pharmacotherapy (e.g. MPH) or were treatment naïve. In these studies, short-term treatment with flexibly-dosed lisdexamfetamine demonstrated greater efficacy than atomoxetine, based on a prospective comparison, and osmotic-release oral system (OROS)-MPH, based on a post hoc comparison. Improvements in ADHD symptoms were accompanied by improvements in health-related quality of life and functioning that were maintained as long as treatment with lisdexamfetamine was continued in a long-term extension of one of these trials. In subsequent phase IV head-to-head studies in adolescents with ADHD and an inadequate response to previous pharmacotherapy, lisdexamfetamine demonstrated greater efficacy than OROS-MPH when both medications were force-titrated, but not when they were flexibly-titrated. Lisdexamfetamine was generally well tolerated, with an adverse event profile (e.g. decreased appetite, headache, weight reduction, insomnia and irritability) typical of that reported for other stimulants. Thus, lisdexamfetamine provides an alternative option for the treatment of children and/or adolescents with ADHD who have not responded adequately to previous ADHD pharmacotherapies.

Attention deficit hyperactivity disorder pharmacotherapy in Slovenian adults: a population-based study.

Background Pharmacotherapy is the first line treatment for adult attention deficit hyperactivity disorder (ADHD) and the percentage of treated patients may indicate the quality of treatment of adult ADHD. The main aim of this study was to investigate the rates of pharmacological treatment for adult ADHD in Slovenia from 2003 to 2015.Methods The number of prescriptions per patient was obtained for three different age groups (18-24, 25-49, 50+age group). The national consumption rates were obtained from the national database. The only drugs that were available and were included in this study were methylphenidate (MPH) and atomoxetine (ATX).Results Between 2003 and 2015 the rate of patients aged 18-24 who were treated with MPH increased from 0.8 per 10,000 people aged 18-24 to 8.9 per 10,000 people, while the increase in the other two age groups was less substantial (25-49, 50+age group). The rate of patients aged 18-24 treated with ATX in 2015 was 7.3 per 10,000 people and 2.2 per 10,000 people in the 25-49 age category and 0.28 in the 50+age group category.Conclusion Prescription rates of ADHD medication have increased dramatically in the study period. The high proportion of ADHD patients treated with ATX can be explained by low adherence to treatment guidelines. This is the first study to compare ADHD pharmacotherapy across different adult age groups in this part of Europe, so the results could be widely relevant.

Diagnoses of Cardiovascular Disease or Substance Addiction/Abuse in US Adults Treated for ADHD with Stimulants or Atomoxetine: Is Use Consistent with Product Labeling?

BackgroundAmong US adults, utilization of pharmacotherapy for attention-deficit hyperactivity disorder (ADHD) has increased more than ninefold since 1995–1996. Potential contraindications to ADHD pharmacotherapy include serious cardiovascular disease (CVD) and, for stimulants, addictions and bipolar disorder (BPD).ObjectiveTo assess the prevalence of potential contraindications among adults treated with ADHD pharmacotherapy.MethodsA retrospective cohort analysis was performed using the Truven Health MarketScan® database. Subjects filled ≥ 1 prescription for atomoxetine or ≥ 1 stimulant in 2014–2015, were aged 18–64 years, commercially insured throughout observation, and diagnosed with ADHD on two or more medical claims. Diagnoses and medical procedures were measured in the 12 months prior to pharmacotherapy initiation. Metrics included serious CVD (cardiomegaly, cardiomyopathy, cerebrovascular occlusion, congestive heart failure, myocardial infarction, pacemaker, or valvular disorder) and any CVD (serious CVD, other atherosclerotic CVD, arrhythmia, congenital heart anomaly, or hypertensive heart disease). Rates of substance addiction or abuse were measured in a range to address nonspecific diagnostic coding.ResultsOnly 2.0% of treated adults (n = 91,588) had one or more diagnosis indicating serious CVD. CVD prevalence increased monotonically with age. Of patients aged 55–64 years (n = 5,237), 7.2% had serious CVD; 15.9% had any CVD; and 1.9% had been hospitalized with one or more CVD. Of patients treated with stimulants (n = 87,167), 11.3–18.5% were diagnosed with addiction/abuse and 4.1% with BPD.ConclusionsCVD prevalence is generally low among adults using ADHD medication but increases with age. Although difficult to estimate precisely, the rate of addiction/abuse among stimulant-treated patients appears unexpectedly high. Further research should assess cardiovascular events and other potential harms associated with contraindicated use in high-risk adults.Electronic supplementary materialThe online version of this article (10.1007/s40801-017-0129-2) contains supplementary material, which is available to authorized users.

Racial-Ethnic Differences in Patterns of Discontinuous Medication Treatment Among Medicaid-Insured Youths With ADHD.

This study examined the association between race-ethnicity and patterns of medication gaps and discontinuities among Medicaid-insured children initiating pharmacotherapy for attention-deficit hyperactivity disorder (ADHD). Medicaid claims data from nine states were used to identify racial-ethnic differences in patterns of ADHD medication treatment among 102,669 children initiating ADHD medication. Multinomial logistic regression with state indicators was used to estimate these differences, with adjustment for individual and contextual confounders. Approximately three-fifths of the sample did not receive continuous medication treatment as defined by HEDIS guidelines; among them, one-fifth discontinued treatment with no subsequent reinitiation (early termination), less than one-tenth reinitiated pharmacotherapy following a single medication gap, more than three-tenths experienced discontinuous pharmacotherapy with two gaps, and more than four-tenths experienced discontinuous pharmacotherapy with three or more gaps. Compared with white children, black children had a 25% relative increase in the likelihood of early termination and Hispanic children had a 21% relative increase (p<.001); their relative increases in the likelihood of two medication gaps were 41% and 29%, respectively (p<.001), and for three or more gaps they were 56% and 40%, respectively (p<.001). Black and Hispanic children were much more likely than white children to be classified as discontinuing ADHD medication treatment, according to HEDIS. The differences predominantly occurred because youths from minority groups were more likely to experience multiple medication gaps, rather than complete discontinuation. Future studies should examine reasons for these multiple gaps to inform interventions to improve ADHD treatment continuity.

Do Pharmaceuticals Improve Driving in Individuals with ADHD? A Review of the Literature and Evidence for Clinical Practice.

Attention-deficit/hyperactivity disorder (ADHD) is defined as a disorder of impaired attention and/or behavioral control. Studies suggest that the condition can dispose individuals to a higher risk of automobile accidents. ADHD symptoms respond to pharmacotherapy in a majority of uncomplicated cases. Evidence on how pharmacotherapies for ADHD impact driving behavior or outcomes could allow clinicians to support on-road safety rationally. We therefore undertook a review to identify the evidence base to date indicating positive or negative effects of pharmacotherapies on driving behavior in individuals with ADHD. Further, we evaluated the level of evidence for these effects, their specificity to ADHD, and how they may inform clinical care. We identified studies involving pharmacotherapy for ADHD that evaluated driving-related activities or outcomes. We then categorized these studies by the mode of measurement used and by the ADHD specificity of the driving behaviors measured. Finally, we extracted themes of interest to clinical practice in pharmacologic intervention. In total, 14 studies, involving 2-61 subjects diagnosed with ADHD, looked at computer-measured, observer-measured, or self-reported driving behavior correlates of pharmacotherapy during simulation or on-road driving. Of these studies, 13 involved psychostimulant agents and two used atomoxetine. All but three investigations (one of methylphenidate, one of mixed amphetamine salts, and one of atomoxetine) found favorable changes in measures such as steering and braking behaviors or reaction to unexpected events. One study found adverse effects on driving at hour 17 following mixed amphetamine salt administration. Four studies compared two pharmacotherapies, and each found differences in measured driving behavior between the therapies. One study explored impact on ADHD-specific driving impairments, and the same study was the only one to explore correlation of clinical measures (ADHD symptoms and self-reported driving behavior) with medication-associated changes-finding dissociation between changes in ADHD symptoms and changes in measured driving measures. While data to date are limited on the ADHD-specific effects of pharmacotherapies used for ADHD on driving, it is clear from our review that these agents have effects on driving-relevant behaviors. Further research is urgently needed to develop an evidence base for clinically predictable effects of pharmacotherapy on driving safety in individuals with ADHD. If possible, clinicians should evaluate the positive and negative effects of pharmacotherapy on driving in their clients.

The Clinical Pharmacokinetics of Amphetamines Utilized in the Treatment of Attention-Deficit/Hyperactivity Disorder.

Amphetamine (AMP), an indirectly acting psychostimulant approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults, is among the most long-standing therapeutic agents in all of clinical psychopharmacology. This review focuses on AMP absorption, metabolism, and elimination brought to bear on comparative pharmacokinetics in its various formulations. A comprehensive search of the published literature was conducted using MEDLINE (PubMed) and Google Scholar databases through April 2017 to retrieve all pertinent in vitro and human studies for review and synthesis. Additionally, Food and Drug Administration (FDA) databases were accessed for otherwise unavailable data when possible. Initially available as racemic (dl)-AMP, this drug was later supplanted by enantiopure (d)-AMPH or enantioenriched (75:25 dl)-AMP formulations; although racemic AMP returned as an approved drug to treat ADHD in 2014. Presently, there are several immediate-release (IR) formulations available, including d-AMP, dl-AMP, and mixed amphetamine salts, which are neither racemic nor the pure d-enantiomer (i.e., a 3:1 mixture of d-AMP and l-AMP). Furthermore, new modified-release AMP formulations, including an oral suspension and an orally disintegrating tablet, are now available. A lysine-bonded prodrug form of d-AMP also serves as a treatment option. Oral AMP is rapidly absorbed, with high absolute bioavailability, followed by extensive metabolism involving multiple enzymes. Some metabolic pathways exhibit stereoselective biotransformations favoring the l-isomer substrate. Drug exposure exhibits dose-proportional pharmacokinetics. Body weight is a fundamental determinant of differences in observed AMP plasma concentrations. IR formulations typically provide a Tmax from 2 to 3 hours. In replicated studies, children exhibit a shorter plasma T1/2 (∼7 hours) relative to adults (∼10 to 12 hours). There are few documented pharmacokinetic drug interactions of clinical significance beyond influences of drug-induced alteration of urinary pH. The array of AMP formulations addressed in this review offer flexibility in dosing, drug onset, and offset to assist in individualized pharmacotherapy of ADHD.

Nuevos tratamientos farmacológicos en el TDAH. A propósito de un caso clínico

El Trastorno por Déficit de Atención/Hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo más prevalentes en la infancia que frecuentemente se mantiene en la adolescencia y edad adulta. Los psicoestimulantes son generalmente el tratamiento farmacológico de primera línea para el TDAH, aunque alguno de estos pacientes no consiguen una remisión sintomática completa, especialmente los que tienen comorbilidad con el Trastorno Negativista Desafiante (TND). En estos casos, hay cada vez una mayor evidencia de que la combinación de psicoestimulantes y medicamentos no específicos para manejar el TDAH puede ser útil. La Guanfacina de liberación prolongada (GXR, Guanfacine Extended Release), un nuevo fármaco no psicoestimulante que actúa como agonista alfa 2 adrenérgico, ha sido aprobado recientemente por la Agencia Europea de Medicamentos como un nuevo tratamiento para el TDAH. En España se ha empezado a comercializar a finales de enero 2017. El objetivo de este estudio es evaluar la eficacia y tolerabilidad de la GXR administrada conjuntamente con dimesilato de lisdexanfetamina en un paciente con Trastorno por Déficit de atención e Hiperactividad (TDAH) y Trastorno Negativista Desafiante(TND).

Effects of stimulants and atomoxetine on emotional lability in adults: A systematic review and meta-analysis

BackgroundEmotional lability (EL) is an associated feature of attention-deficit/hyperactivity disorder (ADHD) in adults, contributing to functional impairment. Yet the effect of pharmacological treatments for ADHD on EL symptoms is unknown. We conducted a systematic review and meta-analysis to examine the effects of stimulants and atomoxetine on symptoms of EL and compare these with the effects on core ADHD symptoms. MethodsA systematic search was conducted on the databases Embase, PsychInfo, and Ovid Medline® and the clinicaltrials.gov website. We included randomised, double-blind, placebo-controlled trials of stimulants and atomoxetine in adults aged 18–60 years, with any mental health diagnosis characterised by emotional or mood instability, with at least one outcome measure of EL. All identified trials were on adults with ADHD. A random-effects meta-analysis with standardised mean difference and 95% confidence intervals was used to investigate the effect size on EL and compare this to the effect on core ADHD symptoms. ResultsOf the 3,864 publications identified, nine trials met the inclusion criteria for the meta-analysis. Stimulants and atomoxetine led to large mean weighted effect-sizes for on ADHD symptoms (n=9, SMD=−0.8, 95% CI:−1.07 to −0.53). EL outcomes showed more moderate but definite effects (n=9, SMD=−0.41, 95% CI:−0.57 to −0.25). ConclusionsIn this meta-analysis, stimulants and atomoxetine were moderately effective for EL symptoms, while effect size on core ADHD symptoms was twice as large. Methodological issues may partially explain the difference in effect size. Reduced average effect size could also reflect heterogeneity of EL with ADHD pharmacotherapy responsive and non-responsive sub-types. Our findings indicate that EL may be less responsive than ADHD symptoms overall, perhaps indicating the need for adjunctive psychotherapy in some cases. To clarify these questions, our findings need replication in studies selecting subjects for high EL and targeting EL as the primary outcome.

The Impact of Pharmacotherapy on Substance Use in Adolescents With Attention-Deficit/Hyperactivity Disorder: Variations Across Subtypes

ABSTRACTObjective: The primary purpose of this study was to investigate the impact of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy on the risk of substance use within each ADHD subtype. Methods: The study used data from the National Comorbidity Survey-Adolescent supplement, a nationally representative sample of US adolescents (ages 13–18) collected from 6,483 adolescent-parent interviews conducted between 2001 and 2004. ADHD was categorized into three subtypes: ADHD-predominantly hyperactive-impulsive type (ADHD-H); ADHD-predominantly inattentive type (ADHD-I); and ADHD-combined type (ADHD-C) using Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Substance use information was obtained from the adolescents’ interview. The impact of ADHD-pharmacotherapy on substance use was examined using multivariable logistic regression analysis. Results: Among the adolescents with ADHD, ADHD pharmacotherapy significantly associated with reduced risk of substance use (OR = 0.53, 95%CI [0.31–0.90]); with regards to ADHD subtypes, ADHD pharmacotherapy is negatively associated with substance use in adolescents with ADHD-C (OR = 0.53, 95%CI [0.24–0.97]) and those with ADHD-H (OR = 0.23, 95% CI [0.07–0.78]), but it did not have statistically significant effect on risk of substance use in those with ADHD-I subtype (OR = 0.49, 95%CI [0.17–1.39]). Among the group who never received ADHD-pharmacotherapy before the interview, individuals with ADHD-H and ADHD-C had a similar risk of substance use compared to adolescents with ADHD-I (ADHD-C: OR = 1.5, 95%CI [0.77–2.95] and ADHD-H: OR = 2.10, 95%CI [0.87–4.95]). Conclusions: Adolescents with ADHD were equally susceptible to future substance use disregard their ADHD subtypes. Receipt of pharmacotherapy could decrease risk of substance use in adolescents with ADHD-H and ADHD-C, but it may not affect risk of substance use among individuals with ADHD-I.

Pharmacological Treatment of ADHD in Addicted Patients: What Does the Literature Tell Us?

After participating in this activity, learners should be better able to:• Evaluate pharmacologic treatment of attention deficit/hyperactivity disorder (ADHD) in patients with substance use disorder (SUD) • Assess the causes of the diminished efficacy of ADHD medication in patients with comorbid SUD OBJECTIVE: Substance use disorder (SUD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur, and the presence of ADHD complicates the treatment of the addiction. Pharmacotherapy is a potent intervention in childhood and adult ADHD, but findings have been mixed in adolescent and adult ADHD patients with SUDs. This review focuses on several contributing factors and possible explanations, with implications both for future research and for clinical practice. This systematic review examined all randomized, placebo-controlled trials of pharmacotherapy for ADHD in adult and adolescent SUD patients. The number of studies is limited, and several studies are hampered by qualitative flaws. The results, in general, are inconclusive for most medications studied, but more recent trials using psychostimulants in robust dosing have demonstrated significantly positive results. In reviewing these trials, possible explanations relating to the particular characteristics and problems of this complex patient group are discussed. Several factors, including ADHD symptom severity, psychiatric comorbidity, persistent drug use, choice of medication, and concomitant psychosocial intervention, influence study results. Taking these factors into account may improve the likelihood of detecting significant effects in future research, as the recent positive trials have indicated, and may help in the appropriate selection of pharmacotherapy in clinical practice.

Access to diagnosis, treatment, and supportive services among pharmacotherapy-treated children/adolescents with ADHD in Europe: data from the Caregiver Perspective on Pediatric ADHD survey.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders and negatively impacts caregivers’ lives. Factors including barriers to accessing care, dissatisfaction with support services, and lack of caregiver resources may contribute to this.ObjectivesTo report caregivers’ experiences of ADHD diagnosis, behavioral therapy (BT), and supportive care for children/adolescents with ADHD.MethodsThe Caregiver Perspective on Pediatric ADHD (CAPPA) survey included caregivers of children/adolescents (6–17 years) from ten European countries who were currently receiving/had received ADHD pharmacotherapy in the previous 6 months. Caregivers reported experiences of obtaining an ADHD diagnosis, access to BT, availability of caregiver resources, and level of health care/school support. Pan-EU and country-specific descriptive statistics are reported; responses were compared across countries.ResultsOf 3,616 caregivers, 66% were female. Mean age of children/adolescents was 11.5 years; 80% were male. Mean time from the first doctor visit to diagnosis was 10.8 (95% confidence interval 10.2, 11.3) months; 31% of caregivers reported the greatest degrees of difficulty in obtaining an ADHD diagnosis; 44% of children/adolescents did not receive BT. Forty-seven percent of caregivers reported that sufficient resources were available, 44% were “very satisfied”/“satisfied” with medical care, and 50% found health care providers “very supportive”/“somewhat supportive”. Mainstream schools were attended by 82% of children/adolescents. Of those, 67% of caregivers thought schools could help more with the child/adolescent’s ADHD and 48% received extra help/special arrangement. Results varied significantly between countries (P<0.001, all parameters).ConclusionAlmost a third of caregivers reported a high degree of difficulty in obtaining an ADHD diagnosis for their child/adolescent, less than half felt that sufficient resources were available, and gaps in support from health care providers/schools were identified. Findings underscore the need to improve access to diagnosis and provision of supportive services to enable better standards of care, and potentially reduce the impact of child/adolescent ADHD on caregivers’ lives.

Factors associated with caregiver burden among pharmacotherapy-treated children/adolescents with ADHD in the Caregiver Perspective on Pediatric ADHD survey in Europe.

BackgroundBurden on caregivers of children/adolescents with attention-deficit/hyperactivity disorder (ADHD) is multidimensional, but incompletely understood.ObjectiveTo analyze caregiver burden across the concepts of work, social/family life, and parental worry/stress, in relation to selected contributing factors.MethodsThe online Caregiver Perspective on Pediatric ADHD survey was fielded in ten European countries. Analysis included children/adolescents (6–17 years) who were receiving/had received ADHD pharmacotherapy in the previous 6 months. Caregivers recorded their child’s/adolescent’s symptoms “on”/“off” medication (ie, when the caregiver reported that the child/adolescent forgot/chose not to take medication, before the onset of medication effect, or medication worn off). Effects of ADHD severity, comorbidities, and medication adherence on each burden outcome were assessed (multiple regression models).ResultsIn total, 2,326 caregivers were included (children/adolescents’ mean age: 11.5 years, 80% male). Caregivers reported missed/altered work, avoiding social activity, increased parental worry/stress, and strain on family life, despite using ADHD pharmacotherapy. Child/adolescent comorbidities and ADHD severity were significantly related to all burden concepts measured; the strongest comorbidity associations were with altered work (odds ratios [ORs] =1.68 [95% confidence interval {CI} 1.33, 2.12], 1.87 [1.37, 2.54], 3.47 [2.51, 4.78] for 1, 2, 3+ comorbidities, respectively) and planning the day around the child/adolescent (OR =1.42 [95% CI 1.17, 1.72], 1.73 [1.33, 2.15], 2.65 [1.99, 3.53]); the strongest severity associations were: quitting a job (OR =1.41 [95% CI 1.26, 1.59]) and planning a day around the child/adolescent (OR =1.26 [95% CI 1.20, 1.32]). Increased medication adherence was most associated with reducing the caregiver burden for altered work (OR =0.57 [95% CI 0.45, 0.72]), worrying about how they are being perceived as a parent (OR =0.68 [0.56, 0.83]), and avoiding social activity (OR =0.56 [0.45, 0.68]), but not family or stress burden.ConclusionBurdens related to work, social activity, family life, and parental worry/stress were experienced by the caregivers of children/adolescents with ADHD, despite using ADHD pharmacotherapy. Better understanding of clinical/treatment characteristics most associated with the components of caregiver burden may help improve ADHD management and may ease caregiver burden.

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.

Treatment Controversies in Adult ADHD.

Treatment Controversies in Adult ADHD.

Seasonal Patterns of Medications for Treating Attention-Deficit/Hyperactivity Disorder: Comparison of Methylphenidate and Atomoxetine

PurposeMedication is a first-line effective treatment for attention-deficit/hyperactivity disorder (ADHD). Currently, immediate-release methylphenidate (IR-MPH), the osmotic, controlled-release formulation of methylphenidate (OROS-MPH), and atomoxetine (ATX) are the only 3 medications approved in Taiwan for the treatment of ADHD. Short-term discontinuation of ADHD treatment is often seen among patients undergoing drug therapy. The goal of this study was to evaluate potential seasonal patterns in ADHD prescriptions and compare the seasonal changes of IR-MPH, OROS-MPH, and ATX use. MethodsTaiwan’s National Health Insurance database was used to gather information on patients diagnosed with ADHD (N = 145,269) from January 2000 to December 2011. The monthly data regarding person-days and receipt of treatment with IR-MPH, OROS-MPH, and ATX were analyzed. Time series analyses and autoregressive integrated moving average models were used to examine the seasonal patterns in person-days receiving ADHD pharmacotherapy. A general linear model with a post hoc test was used to determine the differences in monthly consumption of ADHD medications. FindingsThis study comprised 145,269 patients (mean age: 7.7 years; 78.6% were boys) diagnosed with ADHD. The prescriptions of IR-MPH (seasonal autoregressive: estimate [SE], 0.92 [0.04], t = 22.87, P < 0.001) and OROS-MPH (estimate [SE], 0.84 [0.09], t = 9.41, P < 0.001) both showed significant seasonal patterns, but ATX prescriptions did not (estimate [SE], 0.50 [0.55]; t = 0.90; P = 0.373). IR-MPH and OROS-MPH prescriptions shared similar seasonal trends. The mean person-days of consumption in July were lower than in other months, with the exception of February and August. Meanwhile, for ATX, the person-days of consumption in February were the lowest. The mean person-days in February were significantly lower than in March and May but did not differ from those in other months. ImplicationsThe seasonal patterns of IR-MPH and OROS-MPH use coincide with school holidays. These findings suggest that discontinuing a drug during the holiday period may be popular for people undergoing ADHD pharmacotherapy, especially with regard to methylphenidate prescriptions. However, additional research is necessary to determine whether temporary discontinuation of drug therapy is related to patient outcomes.

Treatment of Comorbid Substance Use Disorders and ADHD in Youth

There has been great interest in the overlap between attention-deficit hyperactivity disorder (ADHD) and substance use disorder (SUD). Studies have shown that ADHD increases the risk of SUD and that 25–40 % of adults and adolescents with SUD have ADHD. The mechanism linking these disorders probably encompasses various behavioral, biologic, and genetic factors. Early pharmacotherapy of ADHD does not increase SUD and in fact, appears to reduce cigarette smoking and SUD. In individuals with ADHD and SUD, stabilization of SUD is recommended initially with consideration of adjunct non-stimulant and extended-release stimulant medications. More research on the mechanisms of overlap between the disorders, preventive effects of early ADHD treatment on SUD, and concurrent treatments for ADHD and SUD are necessary.

Clinical Presentation, Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in Older Adults: A Review of the Evidence and its Implications for Clinical Care.

Although previously considered a disorder of childhood, studies in the last decade have demonstrated that attention-deficit hyperactivity disorder (ADHD) continues to impair function into adulthood and responds to pharmacotherapy. Due to age-specific changes in roles and challenges, it is possible that presentation and response to intervention may differ between older and younger adults. A literature search for papers that identified older adults with ADHD, including papers describing its epidemiology, manifestation, and treatment, was the basis for this paper. There is a paucity of data on ADHD in older adults; however, small observational studies have characterized the presence, impact, and treatment of ADHD in adults over the age of 50years, and larger epidemiologic studies have demonstrated that ADHD symptoms exist in older adulthood. Optimal criteria for diagnosis of ADHD and methods of treating ADHD in older individuals have not been systematically explored. In light of the limited data, this review discusses considerations for differential diagnosis and safe pharmacotherapy of ADHD in older adults.

Guanfacine Extended Release: A New Pharmacological Treatment Option in Europe.

Children/adolescents with attention-deficit/hyperactivity disorder (ADHD) may have a poor or inadequate response to psychostimulants or be unable to tolerate their side-effects; furthermore, stimulants may be inappropriate because of co-existing conditions. Only one non-stimulant ADHD pharmacotherapy, the noradrenaline transporter inhibitor atomoxetine, is currently approved for use in Europe. We review recent advances in understanding of the pathophysiology of ADHD with a focus on the roles of catecholamine receptors in context of the α2A-adrenergic receptor agonist guanfacine extended release (GXR), a new non-stimulant treatment option in Europe. Neuroimaging studies of children/adolescents with ADHD show impaired brain maturation, and structural and functional anomalies in brain regions and networks. Neurobiological studies in ADHD and medication response patterns support involvement of monoaminergic neurotransmitters (primarily dopamine and noradrenaline). Guanfacine is a selective α2A-adrenergic receptor agonist that has been shown to improve prefrontal cortical cognitive function, including working memory. The hypothesized mode of action of guanfacine centres on direct stimulation of post-synaptic α2A-adrenergic receptors to enhance noradrenaline neurotransmission. Preclinical data suggest that guanfacine also influences dendritic spine growth and maturation. Clinical trials have demonstrated the efficacy of GXR in ADHD, and it is approved as monotherapy or adjunctive therapy to stimulants in Canada and the USA (for children and adolescents). GXR was approved recently in Europe for the treatment of ADHD in children and adolescents for whom stimulants are not suitable, not tolerated or have been shown to be ineffective. GXR may provide particular benefit for children/adolescents who have specific co-morbidities such as chronic tic disorders or oppositional defiant disorder (or oppositional symptoms) that have failed to respond to first-line treatment options.

Attention-deficit hyperactivity disorder, its pharmacotherapy, and the risk of developing bipolar disorder: A nationwide population-based study in Taiwan

In this study, we aimed to evaluate the relationship between attention-deficit/hyperactivity disorder (ADHD) during childhood and subsequent diagnoses of bipolar disorder (BD), as well as to determine whether the pharmacotherapy for ADHD (methylphenidate and atomoxetine) influence the risks of developing BD. A nationwide cohort of patients newly diagnosed with ADHD (n = 144,920) and age- and gender-matching controls (n = 144,920) were found in Taiwan's National Health Insurance database from January 2000 to December 2011. Both patients and controls were observed until December 31, 2011. To determine the effect that the duration of methylphenidate and atomoxetine exposure had on BD, the difference in the risk of developing BD was compared among non-users, short-term users (≤365 days), and long-term users (>365 days). In comparison to the control group, the ADHD group showed a significantly increased risk of developing BD (ADHD: 2.1% vs. controls: 0.4%; aHR: 7.85, 95% CI: 7.09–8.70), and had a younger mean age at the time of first diagnosis (ADHD: 12.0 years vs. controls: 18.8 years). Compared to ADHD patients that had never taken methylphenidate, patients with long-term use of methylphenidate were less likely to be diagnosed with BD (aOR: 0.72, 95% CI: 0.65–0.80). However, the duration of exposure to atomoxetine did not have a significant relationship to a BD diagnosis. The results suggested that a previous diagnosis of ADHD was a powerful indicator of BD, particularly juvenile-onset BD. Nevertheless, the exact mechanisms of the relationships among ADHD, its pharmacotherapy, and BD require further clarification in the future.

Long-Term Treatment Outcome in Adult Male Prisoners With Attention-Deficit/Hyperactivity Disorder: Three-Year Naturalistic Follow-Up of a 52-Week Methylphenidate Trial.

Despite high rates of attention-deficit/hyperactivity disorder (ADHD) among adult lawbreakers, particularly the long-term effects of ADHD pharmacotherapy remain unclear, not the least because of ethical challenges with preventing control subjects in randomized controlled trials from receiving medication over prolonged time. We followed up adult male prisoners with ADHD who completed a 5-week randomized, double-blind, placebo-controlled trial followed by a 47-week open-label extension of osmotic-release oral system methylphenidate in a Swedish high-security prison from 2007 to 2010 (ClinicalTrials.gov: NCT00482313). Twenty-five trial completers were prospectively followed up clinically 1 year (24/25, 96% participated fully or in part) and 3 years (20/25, 80% participation) after trial regarding ADHD symptoms (observer and self-reports), psychosocial functioning, substance misuse, and criminal reoffending. Methylphenidate-related improvements in ADHD symptoms and psychosocial functioning obtained during the 52-week trial were maintained at 1- and 3-year follow-ups. Specifically, after 3 years, 75% (15/20) of the respondents had been released from prison, and 67% of these (10/15) had employment, usually full time. In contrast, nonmedicated respondents at the 3-year follow-up (5/20) reported more ADHD symptoms, functional impairment, and substance misuse compared with currently medicated respondents (15/20). Further, 40% of the respondents self-reported reoffending, indicating a substantially lower relapse rate than expected (70%-80%).In summary, although these observations need validation from new and larger samples, positive effects were maintained after 4 years of methylphenidate treatment. Most study completers were employed and had no relapse in substance misuse or criminality. These results suggest that motivational support and continued medication are important for improved outcome in adult criminal offenders with ADHD.