ADHD

Stimulant Management of Attention-Deficit/Hyperactivity Disorder for the Pediatric Prescriber: A Review of Stimulant-Dosing Strategies and An Overview of New Stimulants

Author/s: 
Courtney Romba, Jasleen Singh

Pediatricians are often the first providers to assess and treat attention-deficit/hyper-activity disorder (ADHD) in youth. While a variety of pharmacological and psychosocial interventions exist for ADHD, stimulants remain the first-line medication treatment. Many stimulant formulations now exist, providing the pediatric prescriber with a diverse repertoire of treatment options. This article is tailored to the pediatric prescriber in the primary care setting and discusses stimulant management, with emphasis on dosing equivalencies, common stimulant-dosing strategies, and newer stimulants.

ADHD Pharmacotherapy and Mortality in Individuals With ADHD

Author/s: 
Lin Li, Nanbo Zhu, Le Zhang, Ralf Kuja-Halkola, Brian M D'Onofrio, Isabell Brikell, Paul Lichtenstein, Samuele Cortese, Henrik Larsson, Zheng Chang

Importance: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk.

Objective: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD.

Design, setting, and participants: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first.

Exposures: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis.

Main outcomes and measures: We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings).

Results: Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05).

Conclusions and relevance: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

Autism Spectrum Disorder: A Review

Author/s: 
Hirota, T., King, B. H.

Importance: Autism spectrum disorder (ASD), characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests, is a neurodevelopmental disorder affecting approximately 2.3% children aged 8 years in the US and approximately 2.2% of adults. This review summarizes evidence on the diagnosis and treatment of ASD.

Observations: The estimated prevalence of ASD has been increasing in the US, from 1.1% in 2008 to 2.3% in 2018, which is likely associated with changes in diagnostic criteria, improved performance of screening and diagnostic tools, and increased public awareness. No biomarkers specific to the diagnosis of ASD have been identified. Common early signs and symptoms of ASD in a child's first 2 years of life include no response to name when called, no or limited use of gestures in communication, and lack of imaginative play. The criterion standard for the diagnosis of ASD is a comprehensive evaluation with a multidisciplinary team of clinicians and is based on semistructured direct observation of the child's behavior and semistructured caregiver interview focused on the individual's development and behaviors using standardized measures, such as the Autism Diagnostic Observation Schedule-Second Edition and the Autism Diagnostic Interview. These diagnostic measures have sensitivity of 91% and 80% and specificity of 76% and 72%, respectively. Compared with people without ASD, individuals with ASD have higher rates of depression (20% vs 7%), anxiety (11% vs 5%), sleep difficulties (13% vs 5%), and epilepsy (21% with co-occurring intellectual disability vs 0.8%). Intensive behavioral interventions, such as the Early Start Denver Model, are beneficial in children 5 years or younger for improvement in language, play, and social communication (small to medium effect size based on standardized mean difference). Pharmacotherapy is indicated for co-occurring psychiatric conditions, such as emotion dysregulation or attention-deficit/hyperactivity disorder. Risperidone and aripiprazole can improve irritability and aggression (standardized mean difference of 1.1, consistent with a large effect size) compared with placebo. Psychostimulants are effective for attention-deficit/hyperactivity disorder (standardized mean difference of 0.6, consistent with a moderate effect size) compared with placebo. These medications are associated with adverse effects including, most commonly, changes in appetite, weight, and sleep.

Conclusions and relevance: ASD affects approximately 2.3% of children aged 8 years and approximately 2.2% of adults in the US. First-line therapy consists of behavioral interventions, while co-occurring psychiatric conditions, such as anxiety or aggression, may be treated with specific behavioral therapy or medication.

Attention Deficit Hyperactivity Disorder: Diagnosis and Treatment in Children and Adolescents Comparative Effectiveness Review No. 203

Author/s: 
Kemper, AR, Maslow, GR, Hill, S, Namdari, B, Allen LaPoint, NM, Goode, AP, Coeytaux, RR, Befus, D, Kosinski, AS, Bowen, SE, McBroom, AJ, Lallinger, KR, Sanders, GD

Objectives. Attention deficit hyperactivity disorder (ADHD) is a common pediatric neurobehavioral disorder often treated in the primary care setting. This systematic review updates and extends two previous Agency for Healthcare Research and Quality (AHRQ) systematic evidence reviews and focuses on the comparative effectiveness of methods to establish the diagnosis of ADHD, updates the comparative effectiveness of pharmacologic and nonpharmacologic treatments, and evaluates different monitoring strategies in the primary care setting for individuals from birth through 17 years of age.

Data sources. We searched PubMed®, Embase®, PsycINFO®, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1, 2011, through November 7, 2016.

Review methods. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects when sufficient data were available for meta-analysis.

Results. Evidence was contributed from 103 articles describing 90 unique studies. Twenty-one studies related to diagnosis, 69 studies related to treatment, and no studies were identified on monitoring. The Attention and Executive Function Rating Inventory and Childhood Executive Functioning Inventory performed better than the Cambridge Neuropsychological Test Automated Battery for the diagnosis of ADHD for ages 7–17 years (strength of evidence [SOE]=low). Evidence was insufficient on the use of electroencephalography (EEG) or neuroimaging to establish the diagnosis of ADHD for ages 7–17 years. No studies directly assessed the harms to children labeled as having ADHD. Limited additional evidence published since the original 2011 report was available on ADHD medications approved by the Food and Drug Administration (FDA) compared with placebo or compared to different FDA-approved ADHD medications (SOE=insufficient). For atomoxetine and methylphenidate, the most commonly reported adverse events were somnolence and mild gastrointestinal problems. Atomoxetine had slightly higher gastrointestinal effects than methylphenidate (SOE=low). Cognitive behavioral therapy improved ADHD symptoms (SOE=low). Child or parent training improved ADHD symptoms (SOE=moderate) but made no difference in academic performance (SOE=low). Omega-3/6 fatty acid supplementation made no difference in ADHD symptoms (SOE=moderate). Across all treatments, little evidence was reported on the risk of serious adverse events, including cardiovascular risk.

Conclusions. The 2011 AHRQ systematic review highlighted the benefit of psychostimulants for children 6–12 years of age with ADHD for up to 24 months and found that adding psychosocial/behavioral interventions to psychostimulants is more effective than psychosocial/behavioral interventions alone for children with ADHD and oppositional defiant disorder. This targeted update found insufficient evidence regarding new approaches to the diagnosis (e.g., EEGs, neuroimaging). Little is known about the impact of being labeled as having ADHD. Although cognitive behavioral therapy or child or parent training may decrease symptoms of ADHD, more information is needed regarding the relative benefit of these approaches compared to, or combined with, medication treatment. Omega-3/6 supplementation does not appear to improve ADHD outcomes. No information was identified regarding the optimal strategy for monitoring after diagnosis.

Treatment of Adult ADHD: A Clinical Perspective

Author/s: 
Geffen, Josh, Forster, Kieran

Adult attention deficit/hyperactivity disorder (ADHD) has moved from the blurred edge of clinical focus to clear recognition as a prevalent and significant disorder in its own right. It is a relatively common comorbidity which if identified and treated may open the door to better outcomes for hard-to-treat patients. Conversely, failure to identify and treat adult ADHD is linked to negative outcomes. The recognition of the importance of adult ADHD in a subset of our patients challenges us to overcome our anxiety about this diagnosis and prevent the societal marginalization of vulnerable patients. Adult ADHD responds well to integrated pharmacological and psychotherapeutic intervention. Its treatment responsiveness reduces disability and allows the comorbidity which is typically present to be addressed. Mastering this challenge can make the diagnosis and treatment of adult ADHD a rewarding experience.

The World Health Organization Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale for DSM-5

Author/s: 
Ustun, Berk, Adler, Lenard A., Rudin, Cynthia, Faraone, Stephen V., Spencer, Thomas J., Berglund, Patricia, Gruber, Michael J., Kessler, Ronald C.

IMPORTANCE:

Recognition that adult attention-deficit/hyperactivity disorder (ADHD) is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD screening scales for use in community, workplace, and primary care settings. However, these scales are all calibrated to DSM-IV criteria, which are narrower than the recently developed DSM-5 criteria.

OBJECTIVES:

To update for DSM-5 criteria and improve the operating characteristics of the widely used World Health Organization AdultADHD Self-Report Scale (ASRS) for screening.

DESIGN, SETTING, AND PARTICIPANTS:

Probability subsamples of participants in 2 general population surveys (2001-2003 household survey [n = 119] and 2004-2005 managed care subscriber survey [n = 218]) who completed the full 29-question self-report ASRS, with both subsamples over-sampling ASRS-screened positives, were blindly administered a semistructured research diagnostic interview for DSM-5 adult ADHD. In 2016, the Risk-Calibrated Supersparse Linear Integer Model, a novel machine-learning algorithm designed to create screening scales with optimal integer weights and limited numbers of screening questions, was applied to the pooled data to create a DSM-5 version of the ASRS screening scale. The accuracy of the new scale was then confirmed in an independent 2011-2012 clinical sample of patients seeking evaluation at the New York University Langone Medical Center Adult ADHD Program (NYU Langone) and 2015-2016 primary care controls (n = 300). Data analysis was conducted from April 4, 2016, to September 22, 2016.

MAIN OUTCOMES AND MEASURES:

The sensitivity, specificity, area under the curve (AUC), and positive predictive value (PPV) of the revised ASRS.

RESULTS:

Of the total 637 participants, 44 (37.0%) household survey respondents, 51 (23.4%) managed care respondents, and 173 (57.7%) NYU Langone respondents met DSM-5 criteria for adult ADHD in the semistructured diagnostic interview. Of the respondents who met DSM-5 criteria for adult ADHD, 123 were male (45.9%); mean (SD) age was 33.1 (11.4) years. A 6-question screening scale was found to be optimal in distinguishing cases from noncases in the first 2 samples. Operating characteristics were excellent at the diagnostic threshold in the weighted (to the 8.2% DSM-5/Adult ADHD Clinical Diagnostic Scale population prevalence) data (sensitivity, 91.4%; specificity, 96.0%; AUC, 0.94; PPV, 67.3%). Operating characteristics were similar despite a much higher prevalence (57.7%) when the scale was applied to the NYU Langone clinical sample (sensitivity, 91.9%; specificity, 74.0%; AUC, 0.83; PPV, 82.8%).

CONCLUSIONS AND RELEVANCE:

The new ADHD screening scale is short, easily scored, detects the vast majority of general population cases at a threshold that also has high specificity and PPV, and could be used as a screening tool in specialty treatment settings.

Keywords 
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