Attention-deficit/hyperactivity Disorder Pharmacotherapy Research Articles

First-Time Users of ADHD Medication Among Children and Adolescents in Germany: An Evaluation of Adherence to Prescribing Guidelines Based on Claims Data.

Background: Drug utilization studies based on real-world data are vital for the identification of potentially needed improvements to rational prescribing. This is particularly important for the pharmacological treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD) due to the associated potential side effects and the frequent use. Whereas prevalent use is well-characterized, studies on first-time use of ADHD medication are scarce. This study aimed to evaluate off-label prescribing in first-time users of ADHD medication among children and adolescents in Germany based on three criteria: (i) lack of a documented ADHD diagnosis; (ii) first-time pharmacological treatment with a second-line drug; and (iii) patient age below 6 years.Methods: Based on German claims data, we included children and adolescents aged 0–17 years with a first-time dispensation of any ADHD medication in the period 2015–2017. These first-time users were characterized with regard to sex, age, specialty of the prescribing physician, documentation of an ADHD diagnosis, psychiatric hospitalization, psychiatric comorbidities, and history of other psychopharmacological drugs at first-time use.Results: The study population comprised 18,703 pediatric first-time users of ADHD medication. Of these, 9.8% had no documented ADHD diagnosis. Most of the ADHD drug users received first-line ADHD pharmacotherapy (methylphenidate, atomoxetine), whereas 2.6% were prescribed second-line ADHD medication (lisdexamfetamine, guanfacine, dexamfetamine, multiple ADHD drugs) as first drug. Overall, 1.2% of first-time users were aged below 6 years. A total of 12.7% of the study population met any off-label criterion.Conclusions: About 13% of pediatric first-time users of ADHD medication in Germany received an off-label pharmacotherapy at first-time use. Prescribing ADHD medication without a confirmed ADHD diagnosis was the most common of the three assessed off-label criteria. Off-label prescribing regarding drug choice and age of patients only occurred in a small percentage of initial pharmacological ADHD treatment. Our results suggest the need for improvement in rational prescribing, especially with regard to diagnostic requirements.

Disruption of Pharmacotherapy During the Transition from Adolescence to Early Adulthood in Patients with Attention-Deficit/Hyperactivity Disorder: A Claims Database Analysis Across the USA.

Background and ObjectiveAttention-deficit/hyperactivity disorder (ADHD) treatment rates in adults are low, possibly owing to discontinuation of pediatric care due to various circumstances (including inadequate health insurance coverage, poor disease insight, and patient/family resistance, as well as those who manage their ADHD independent of pharmacologic intervention) during the transition from adolescence to adulthood. To improve the understanding of treatment patterns during this transition, this study characterized pharmacotherapy use in patients with ADHD aged 16–21 years.MethodsA retrospective claims analysis of the IBM® MarketScan® Commercial Databases, which represent all census regions of the USA, included patients aged 16–21 years with two or more ADHD diagnoses between 1/1/2008 and 12/31/2017 (one or more diagnoses during the year of age 17) who were continuously enrolled from ages 16–21 years and prescribed ADHD medication for ≥ 6 months at age 17 years. Pharmacotherapy use was assessed longitudinally. Comparisons between ages were conducted using Wilcoxon signed-rank tests and McNemar tests. Treatment discontinuation was estimated using Kaplan–Meier analyses.ResultsThe analysis included 10,292 patients. The overall percentage of patients receiving pharmacotherapy significantly decreased (p < 0.001, regardless of treatment type and presence of co-occurring psychiatric disorders) as patients aged, with a median time to treatment discontinuation of 2.94 years. Among patients using pharmacotherapy at the age of 17 years, more than 30% were no longer using pharmacotherapy at age 21 years. As patients aged, the percentage using long-acting amphetamines or methylphenidates decreased, and the percentage receiving no treatment increased. The percentage of patients with disrupted treatment from age 18 to 21 years ranged from 17.9 to 24.1%. After transitioning to disrupted treatment or no treatment, low percentages of patients returned to pharmacotherapy use (disrupted treatment: 15.7–21.5% per year; no treatment, 2.7–3.8% per year). Across all age groups, statistically significantly greater (p < 0.05) percentages of patients with co-occurring psychiatric disorders used lisdexamfetamine, dextroamphetamine-amphetamine mix short acting, and non-stimulants compared with patients without co-occurring psychiatric disorders. Patients with co-occurring psychiatric disorders remained on ADHD pharmacotherapy longer and switched or augmented their pharmacotherapy more frequently than patients without co-occurring psychiatric comorbidities.ConclusionsPatients rarely reinitiated treatment after pharmacotherapy was disrupted or discontinued, emphasizing the need for increased focus on the management of ADHD as patients transition from adolescence to adulthood.

Pharmacotherapy for Preschool Children with Attention Deficit Hyperactivity Disorder (ADHD): Current Status and Future Directions.

In this review, we consider issues relating to the pharmacological treatment of young children with attention deficit hyperactivity disorder (ADHD). ADHD in preschool-age children has a profound impact on psychosocial function and developmental trajectory. Clinical studies on pharmacotherapies for ADHD in young children have expanded rapidly in the past 2 decades, providing some evidence of efficacy for both psychostimulant and non-psychostimulant medications. However, preschool children may be more susceptible to adverse effects of medications, including growth reduction and cardiovascular side effects. Many questions remain regarding the long-term safety and effectiveness of these interventions; thus more research is needed to help clinicians evaluate the risk-benefit ratio for preschoolers with ADHD. As this body of knowledge grows, providers should consider the level of impairment caused by current symptoms in the risk-benefit analysis. Families should be educated not just about potential effects of medication but known complications of untreated ADHD; parents will likely not fully appreciate the long-term psychological effects of chronic behavioral problems and underachievement on a young child. A blanket "wait and see" approach should be avoided, in order to prevent a permanent loss of self-esteem and motivation that may affect some children throughout their lifespan.

Pharmacotherapy for Attention-Deficit/Hyperactivity Disorder and Retention in Outpatient Substance Use Disorder Treatment: A Retrospective Cohort Study.

To assess the relationship between short- and longer-term retention in outpatient substance use disorder (SUD) treatment and pharmacotherapy for comorbid attention-deficit/hyperactivity disorder (ADHD). In this retrospective cohort study conducted in a single addiction psychiatry clinic, electronic health record data from July 14, 2014, through January 15, 2020, were queried for clinical ADHD diagnosis (DSM-5 criteria), ADHD pharmacotherapy, treatment duration, demographic variables, comorbid psychiatric and SUD diagnoses, and buprenorphine therapy. Individuals with ADHD (n = 203) were grouped by ADHD pharmacotherapy status (171 receiving medication compared to 32 receiving none). Kaplan-Meier and Cox proportional hazards regression analyses were performed and assessed for significance. ADHD was clinically diagnosed in 9.4% of outpatients and was associated with younger age, comorbid cocaine use, and private insurance (P < .001). Individuals receiving no ADHD pharmacotherapy were younger than those receiving medication (P = .003). Compared to no ADHD medication, ADHD pharmacotherapy was associated with greater long-term retention, with apparent group half-lives of 9 months and 36 months, respectively (P < .001). Individuals receiving no ADHD medication had a 4.9-fold increased likelihood of attrition within 90 days (P = .041). Regression analysis showed only ADHD pharmacotherapy to be significantly associated with treatment retention (hazard ratio = 0.59; 95% CI, 0.40-0.86; P = .008). ADHD pharmacotherapy is robustly associated with improved short- and longer-term retention in outpatient SUD treatment. The retrospective, nonrandomized naturalistic study design limits causal inference. Further studies addressing unmeasured covariates and associated risks of treatment in adults with ADHD and SUD are necessary.

Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Lisdexamfetamine in Healthy Adults.

Viloxazine extended-release is a novel nonstimulant under investigation as a potential treatment for attention-deficit/hyperactivity disorder (ADHD). Given the potential for viloxazine extended-release to be co-administered with stimulant ADHD pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine extended-release + lisdexamfetamine dimesylate (lisdexamfetamine) versus viloxazine extended-release and lisdexamfetamine alone. In this single-center, cross-over, open-label trial, healthy, non-ADHD adults received single oral doses of 700 mg viloxazine extended-release alone, 50 mg lisdexamfetamine alone, and a combination of viloxazine extended-release (700 mg) + lisdexamfetamine (50 mg), with blood samples collected over 4 days postadministration. The active drug in viloxazine extended-release (viloxazine) and primary metabolite of lisdexamfetamine (d-amphetamine) were measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events, vital signs, echocardiograms, and clinical laboratory evaluations. Thirty-six adults were enrolled, and 34 completed the trial. The least squares geometric mean ratios are reported as [combination / single drug (90% confidence intervals)]. Viloxazine extended-release: Cmax = 95.96% (91.33-100.82), area under the concentration-time curve from 0 to the last measurable time (AUC0-t) = 99.19% (96.53-101.91), and area under the concentration-time curve from 0 to infinity (AUCinf) = 99.23% (96.61-101.93). Lisdexamfetamine: Cmax = 112.78% (109.93-115.71), AUC0-t = 109.64% (105.25-114.22), and AUCinf = 109.52% (105.19-114.03). All reported adverse events, except 1 (moderate vomiting), were mild in severity. Co-administration of viloxazine extended-release and lisdexamfetamine did not impact the pharmacokinetics of viloxazine or d-amphetamine relative to administration of either drug alone. After single dose administration, the combination appeared to be safe and well tolerated.

Review of Questions Concerning Clinical Drug Interactions in ADHD Treatment From Physicians in Norway.

Pharmacological treatment of attention deficit hyperactivity disorder (ADHD) is challenging due to a wide age span among patients, risk of reduced adherence, and comorbidities like psychiatric disorders and drug addiction. Drugs used for ADHD are associated with risk of interactions and adverse drug reactions due to their potent pharmacological effect. In this brief report we aimed to describe real-world problem areas concerning interactions in pharmacotherapy of ADHD. We reviewed questions to a Norwegian drug information center from physicians concerning drug-drug interactions involving ADHD drugs in the last 10-year period. Questions were retrieved by a combination of indexed and Boolean database searches, in addition to manual inspection. ADHD drugs and interacting drugs were defined according to the Anatomical Therapeutic Chemical (ATC) classification system. Interactions were classified by use of Stockley’s Interactions Checker (SIC). Answers were examined with regard to whether the advice from the drug information center was more restrictive, similar or more liberal than SIC when assessing drug combinations. We retrieved 61 questions that included assessment of 96 drug combinations, and found 33 potential interactions according to SIC. Methylphenidate was involved in more than 50% of the interactions, and interacting drugs were in nearly 70% of the cases from ATC-group N (Nervous system) with antidepressants most frequently involved. Seventy percent of the interactions were pharmacodynamic, and interactions were frequently described as potentially severe although they were based on theoretical evidence. All the 33 interactions could be handled with monitoring or adjusting dose or with informative measures, and none was contraindicated according to SIC. More than 90% of the questions came from physicians in hospitals or outpatient specialist practice, and questions mainly concerned adults. In 75% of the drug combinations that involved ADHD drugs, we found similar advice from SIC and the drug information center. Our results suggest that future drug information efforts in ADHD treatment to clinicians, including specialists in the field, should focus on psychotropic interactions.

Are non-abstinent reductions in World Health Organization drinking risk level a valid treatment target for alcohol use disorders in adolescents with ADHD?

IntroductionAbstinence from drinking represents the primary treatment target for alcohol use disorders (AUD) in youth, but few adolescents who engage in problematic drinking seek treatment. A reduction in World Health Organization (WHO) drinking risk level has been established as valid and reliable non-abstinent treatment target for AUD in adults but remains unstudied in youth. MethodsThe present study used data from the NIDA-CTN-0028 trial to examine associations between reductions in WHO drinking risk level and changes in global functioning and attention-deficit hyperactivity disorder (ADHD) symptoms during treatment in a sample of adolescents (ages 13–18 years) with ADHD and comorbid substance use disorder (SUD) (n = 297, 61% with AUD) receiving a 16-week intervention that combined ADHD pharmacotherapy (OROS-methylphenidate vs. placebo) and drug-focused cognitive-behavioral therapy. ResultsShifts in drinking risk level during treatment were highly variable in adolescents treated for ADHD/SUD, and influenced by AUD diagnostic status. In the total sample, 15% of participants had a 2-level or greater reduction in WHO drinking risk level, with 59% and 24% showing no change or an increase in risk-level during treatment respectively. Achieving at least a 2-level change in WHO drinking risk level during treatment was associated with greater reduction in ADHD symptoms and better functional outcomes. ConclusionsThese findings parallel the adult AUD literature and provide preliminary support for the use 2-level reductions in WHO risk levels for alcohol use as a clinically valid non-abstinent treatment outcome for youth with ADHD and comorbid AUD.

Prevalence and characteristics of South African treatment-seeking patients with substance use disorder and co-occurring attention-deficit/hyperactivity disorder

ABSTRACT Background Attention-Deficit/Hyperactivity Disorder (ADHD) constitutes a significant risk factor for the development of Substance Use Disorders (SUDs). Individuals with both conditions use more substances, and the pattern of substance use seems to differ between individuals with and without ADHD. Research aim and objectives To establish the prevalence of ADHD symptoms in adult South African treatment-seeking patients with SUD, and the pattern of substance use and presence of previous ADHD diagnoses and pharmacotherapy. Methods Adult patients (N = 360) were recruited from rehabilitation facilities and screened using the ADHD Self-Report Scale Symptom Checklist (ASRS-v1.1). Questions included demographics, substance consumption and current/historical use of ADHD-indicated medication. Results A third (36.0%) of patients with SUD screened positive for ADHD – 14.6% had been diagnosed with ADHD prior to admission, and indicated pharmacotherapy, while 68.5% of those screened positive were not hitherto diagnosed with ADHD (p < 0.001). A statistical difference was found for polysubstance use with the ADHD group significantly being treated more frequently for use of more than one substance (p = 0.04). Conclusions and implications High rates of untreated and unrecognized ADHD were found among treatment-seeking SUD patients. Preventative strategies are crucial to reduce substance use and the development of SUD in individuals affected by ADHD.

Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis.

BackgroundAttention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD.MethodsWe searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane’s Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework.ResultsEighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration.ConclusionsOverall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs.RegistrationPROSPERO no. CRD 42015026049

The female side of pharmacotherapy for ADHD-A systematic literature review.

This comprehensive review examined sex differences in prescription rates and efficacy or effectiveness of pharmacotherapy treatment in girls and women with attention deficit hyperactivity disorder (ADHD), while identifying gaps in the scientific knowledge on this topic. A rigorous electronic database search was carried out in order to identify all published studies on female-specific effects of stimulants and non-stimulants in the treatment of ADHD. In total, 2672 studies were screened of which 21 studies (seven on prescription rates, 14 on effects of pharmacotherapy) met the inclusion criteria and were included for analysis. In all seven studies on ADHD prescription rates, girls received significantly less prescriptions than boys, a difference however no longer seen in adults with the exception of one study. Each of the 14 studies on effectiveness / efficacy found at least one sex-difference in the effects of ADHD pharmacotherapy. Several sex-differences are demonstrated in the prescription, usage and efficacy /effectiveness of both stimulant and non-stimulant ADHD pharmacotherapy. A single daily use of MPH may possibly not be optimal for girls with ADHD and ATX may be a promising medication for girls and women with ADHD. The robustness of this result requires further investigation.

Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis.

Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta-analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation. We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha-2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random-effects model. Twenty-five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent-rated: standardized mean difference [SMD]=-.63, 95%CI=-.95,-.30; teacher-rated: SMD=-.81, 95%CI=-1.43,-.19) and inattention (parent-rated: SMD=-.36, 95%CI=-.64,-.07; teacher-rated: SMD=-.30, 95%CI=-.49,-.11). Atomoxetine reduced inattention (parent-rated: SMD=-.54, 95%CI = -.98,-.09; teacher/investigator-rated: SMD=-0.38, 95%CI=-0.75, -0.01) and parent-rated hyperactivity (parent-rated: SMD=-.49, 95%CI=-.76,-.23; teacher-rated: SMD=-.43, 95%CI=-.92, .06). Indirect evidence for significant reductions in hyperactivity with second-generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events. Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long-term continuation is undertaken to help guide clinical decision-making regarding treatment of co-occurring ADHD symptoms in children and youth with ASD.

Pharmacotherapy of attention-deficit hyperactivity disorder: common quandaries, dilemmas and challenges.

Multiple studies have shown that pharmacologic treatments for attention-deficit hyperactivity disorder (ADHD), especially stimulants, are generally effective. There is yet a paucity of empirical data, however, for some common clinical conditions overlooked in the ADHD treatment guidelines. Some examples include: in cases of first line treatment failure, it is unclear whether switching from one type of stimulant to another is beneficial. In cases of comorbid ADHD and severe aggressive/disruptive behavior in children, it is unclear whether the best first-line treatment is stimulants or atypical antipsychotics like risperidone. In cases of ADHD with comorbid anxiety disorders, there is no clear evidence regarding optimal treatment. The objectives of this article are to review these issues and propose possible answers for such clinical dilemmas.

Practical guide and some recommendations for the diagnosis and management of Attention deficit hyperactivity disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD) is described as the most common neurobehavioral condition of childhood. Symptoms include difficulty concentrating, hyperactivity and poorly controlled impulsivity. ADHD always manifests in childhood, children with the syndrome rush around the room, switch their attention from one to the other, cannot calm down and take lessons or reading. ADHD may persist into adulthood causing disruptions to both professional and personal life. The pharmacotherapy of ADHD is cost-effective, but treatment should be individual. Main outlines of clinical practice guide on management of ADHD of Academy of Medicine and Ministry of Health of Singapore are discussed in this article. Some focus on diagnostic process and associated with ADHD problems is emphasized. It can be invaluable example for the specialists engaged in the treatment of the children with this psychiatric disorder.

Attention deficit hyperactivity disorder in childhood and adolescence : Current state of research

Attention deficit hyperactivity disorder (ADHD), defined by the core symptoms impulsiveness, inattention and motor hyperactivity, is one of the most common neurodevelopmental disorders beginning in early childhood. This article reviews the current state of research on the epidemiology, etiology, diagnostics and therapeutic interventions for ADHD in children and adolescents. A selective literature search was carried out in PubMed with reference to the German S3 clinical guidelines on ADHD in children, adolescents and adults. The epidemiological prevalence of ADHD in children is estimated to be 5.3%. The etiology is complex and heterogeneous and ahigh percentage of the phenotypic variance can be explained by genetic influences. The challenge of ADHD diagnostics is to exclude differential diagnoses while simultaneously identifying common coexisting psychiatric conditions. Treatment recommendations depend on the severity of symptoms. In severe ADHD pharmacotherapy should be considered as the first line intervention. Psychostimulants (various methylphenidate and amphetamine preparations) and the non-stimulants atomoxetine and guanfacine are approved in Germany for treatment of ADHD in children and adolescents. In milder cases as well as in preschool children, psychosocial interventions (including behavioral psychotherapy) are often sufficient.

Pharmacotherapy of attention deficit hyperactivity disorder in adults

Pharmacotherapy is acentral component in the context of an overall therapeutic concept in the treatment of adults with attention deficit hyperactivity disorder (ADHD). In this concept psychosocial interventions with psychoeducation or specific psychotherapy measures also play an important role. In adults three compounds are currently approved for the pharmacological treatment of ADHD in Germany. The long-acting stimulants retarded methylphenidate preparations and lisdexamfetamine can be prescribed. Alternatively, the adrenergic uptake inhibitor atomoxetine can be used. In several meta-analyses good effectiveness and tolerance of these drugs on ADHD psychopathology has been shown. They also improve ADHD-related disorders of emotional regulation capability and disorganization in everyday life. Importantly, an improvement in everyday functionality and quality of life under medication could also be shown in several studies. In this review the evidence for pharmacotherapy of ADHD and its implementation into treatment of adult patients is presented.

Suicidal ideation and attempts in the United States of America among stimulant-treated, non-stimulant-treated, and untreated patients with a diagnosis of attention-deficit/hyperactivity disorder

BackgroundStudies of the association between attention-deficit/hyperactivity disorder (ADHD) drug therapy and suicidal ideation and attempts (SIA) have conflicting results. MethodsCohorts of patients with ADHD aged 6 years or older with at least one pharmacy claim for a central nervous system (CNS) stimulant or a non-stimulant, or with no claims for ADHD pharmacotherapy, were identified in the US IBM® MarketScan® Research Database from January 2008 to March 2018. Incidence density rates (IDRs) of SIA (i.e., claims for suicide and self-inflicted poisoning, suicide and self-inflicted injuries, or suicidal ideation) were calculated. Cohorts were compared (CNS stimulants vs non-stimulants; CNS stimulants vs no pharmacotherapy) using hazard ratios (HRs) estimated from Cox proportional hazards models. Inverse-probability-of-treatment weighting (IPTW) was used to control for confounding. ResultsThe study included 797,189 patients (CNS stimulants, 622,536; non-stimulants, 54,615; no pharmacotherapy, 120,038). IDRs of SIA (per 1000 patient-years) were: CNS stimulants, 5.8; non-stimulants, 10.5; and no pharmacotherapy, 10.0. The overall SIA risk was significantly lower with CNS stimulants than with non-stimulants (IPTW-adjusted HR = 0.70, 95% confidence interval = 0.61–0.81, p < 0.001) and no pharmacotherapy (0.62, 0.57–0.67, p < 0.001). LimitationsSIA assessment was based on diagnostic codes; suicidal ideation may not have been reported; completed suicides were generally not captured; and treatment was not verified. ConclusionsIn this population-based study of patients with ADHD, SIA risk was significantly lower in those receiving CNS stimulants relative to those receiving non-stimulants or no pharmacotherapy, suggesting that CNS stimulants may attenuate SIA risk.

Knowledge, Attitudes, and Practice Patterns of Health Professionals Toward Medical and Non-medical Stimulant Use by Young Adults.

The role of family physicians (FPs) and college health professionals (CHPs) in stimulant treatment and nonmedical use of stimulants is not clear. To investigate the current practices, concerns, needs, beliefs, barriers, and facilitators to appropriate pharmacological treatment of teens and young adults with attention deficit hyperactivity disorder (ADHD) and prevention of nonmedical use and diversion. A cross-sectional survey developed by the project team and experts in the field, delivered to national sample of FPs and CHPs. A total of 794 completed surveys were analyzed. The average age of respondents was 51.6 ± 10.3 years; 50.6% of the respondents were female. The majority of CHPs (80.6%) reported they spend 75% to 100% of their time with patients age 17 to 24 years and 74.0% of FPs reported they spend less than 25% of their time with this age group. The majority (91.7%) of the respondents indicated that untreated ADHD affects quality of life, and 76.4% indicated untreated ADHD is often associated with risky behaviors. More CHPs than FPs always refer out for ADHD diagnosis (70.7% vs 52.1%; P < .001). Most respondents (81.2%) were concerned with ADHD medication diversion, and 84.2% believed that diversion or abuse is a problem overall. Respondents indicated they are unprepared to provide patient education on decisions about pharmacotherapy or behavioral therapy choices for adult ADHD. There is an opportunity to enhance safety and effectiveness of ADHD management in young adults. Additional resources and interventions are needed to improve medication management, reduce misuse, and ensure safe and appropriate use of stimulants.

Enhancing the efficacy of 5-HT uptake inhibitors in the treatment of attention deficit hyperactivity disorder

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common childhood behavioural disorders, the frontline treatments for which are drugs with abuse potential. As a consequence, there is an urgent need to develop non addictive drug treatments with equivalent efficacy. Preclinical evidence suggests that selective serotonin uptake inhibitors (SSRIs) are likely to be effective in ADHD, however clinical reports suggest that SSRIs are of limited therapeutic value for the treatment of ADHD. We propose that this disconnect can be explained by the pattern of drug administration in existing clinical trials (administration for short periods of time, or intermittently) leading to inadequate control of the autoregulatory processes which control 5-HT release, most notably at the level of inhibitory 5-HT1A somatodendritic autoreceptors. These autoreceptors reduce the firing rate of 5-HT neurons (limiting release) unless they are desensitised by a long term, frequent pattern of drug administration. As such, we argue that the participants in earlier trials were not administered SSRIs in a manner which realises any potential benefits of targeting 5-HT in the pharmacotherapy of ADHD. In light of this, we hypothesise that there may be under-researched potential to exploit 5-HT transmission therapeutically in ADHD, either through changing the administration regime, or by pharmacological means. Recent pharmacological research has successfully potentiated the effects of SSRIs in acute animal preparations by antagonising inhibitory 5-HT1A autoreceptors prior to the administration of the SSRI fluoxetine. We suggest that combination therapies linking SSRIs and 5-HT1A antagonists are a potential way forward in the development of efficacious non-addictive pharmacotherapies for ADHD.

Association between pharmacotherapy for ADHD in offspring and depression-related specialty care visits by parents with a history of depression

BackgroundPharmacotherapy is effective in reducing the core symptoms of attention-deficit/hyperactivity disorder (ADHD). We aimed to investigate the concurrent association between pharmacotherapy for ADHD in offspring and depression-related specialty care visits by the parents with a history of depression.MethodsUsing data from a variety of Swedish national registers, we conducted a cohort study with 8-year follow-up of 5605 parents (3872 mothers and 1733 fathers) who had a history of depression and an offspring diagnosed with ADHD. The hazard rate for parental depression-related specialty care visits during exposed periods when the offspring was on medication for treatment of ADHD was compared with the hazard rate during unexposed periods when the offspring was off medication. Within-individual comparisons were employed to control for time-constant confounding factors.ResultsAmong mothers, the crude rates of depression-related specialty care visits during exposed and unexposed periods were 61.33 and 63.95 per 100 person-years, respectively. The corresponding rates among fathers were 49.23 and 54.65 per 100 person-years. When the same parent was compared with him or herself, fathers showed a decreased hazard rate for depression-related visits during exposed periods when the offspring was on medication for treatment of ADHD as compared to unexposed periods (hazard ratio, 0.79 [95% confidence interval, 0.70 to 0.90]). No statistically significant associations were observed in mothers.ConclusionsAmong parents with a history of depression, pharmacotherapy for ADHD in offspring is concurrently associated with a decreased rate of depression-related specialty care visits in fathers but not in mothers. Future research with refined measures of parental depression and other time-varying familial factors is needed to better understand the mechanisms underlying the association.

Evaluation and Management of Elevated Blood Pressure in Children and Adolescents with Attention Deficit Hyperactivity Disorder.

To understand the impact of attention deficit hyperactivity disorder (ADHD) and its medications on blood pressure (BP) in children and adolescents and provide recommendations for management of elevated BP in children and adolescents with ADHD. ADHD medications have cardiovascular effects including elevated BP. However, the bulk of the evidence indicates that stimulants and other ADHD medications are safe and do not cause severe cardiovascular diseases. BP should be assessed carefully at the time of ADHD diagnosis, because some behavioral changes similar to ADHD may be associated with hypertension. ADHD medications appear to be safe. However, their long-term impact on the cardiovascular system is not clearly understood and needs further investigation. BP should be monitored regularly during ADHD pharmacotherapy in order to optimize the management of both conditions.