ADHD Prescription Medications and Their Effect on Athletic Performance: A Systematic Review and Meta-analysis

Background Stimulant medications used for the treatment of Attention Deficit-Hyperactivity Disorder (ADHD) are believed to provide a physical advantage in athletics, but several of these medications are not regulated by the World Anti-Doping Association. Given the prevalence of ADHD among the athlete population and concern for abuse of ADHD medications, this review and meta-analysis aimed to evaluate effects of ADHD medications on athletic performance, thereby appraising the validity of claims of performance enhancement. Methods A search of MEDLINE, Embase, CINAHL, and Cochrane Review databases was performed for all randomized controlled trials evaluating athletic performance after ingestion of placebo or ADHD treatment medications from August 2020 through November 2020. All RCTs identified from these search criteria were included for screening, with exclusion of any animal studies. Two reviewers (JB, CK) assessed methodological quality and risk of bias using CONSORT 2010 and Cochrane Collaboration tools. Study results were compiled with corresponding p values for each finding. Effect sizes (Cohen’s D) for athletic performance and physiological changes were aggregated for each study. Studies were further screened for homogeneity that would allow for meta-analysis. Heterogeneity was calculated using I2. Results A total of 13,033 abstracts evaluating amphetamine, methamphetamine, methylphenidate, and bupropion were screened. The final analysis included nine studies, six of which found significant improvement in athletic performance with use of stimulant medications (p < 0.05). Methylphenidate and amphetamine were consistently identified to have a performance effect. Secondary effects identified included significant increase in heart rate, core temperature, and elevation of various serum hormone levels (p < 0.05). Effect size evaluation found seven studies demonstrating small to large effects on physical performance, as well as in categories of cardiometabolic, temperature, hormone, and ratings of perceived exertion, to varying degrees. A meta-analysis was performed on two studies, demonstrating conflicting results. Conclusions Dopaminergic/noradrenergic agonist medications appear to have a positive effect on athletic performance, as well as effects on physiological parameters. Further consideration of medications currently not regulated, i.e. bupropion, is warranted given evidence of athletic performance enhancement. PROSPERO trial registration number: CRD42020211062; 10/29/2020 retrospectively registered.

Primary Care Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder in School-aged Children: Trends and Disparities During the COVID-19 Pandemic

Importance: Little is known about changes in health care in the first year of the pandemic for the large population of school-aged children with attention-deficit/hyperactivity disorder (ADHD), who were especially impacted by lockdowns, school closures, and remote learning. Objective: To assess temporal trends in rates of primary care provider (PCP) diagnosis and treatment of school-aged children with ADHD in the first year of the COVID-19 pandemic as compared to pre-pandemic years, and to investigate disparities in care. Method: We retrospectively analyzed electronic health records from all primary care visits (in-person and telehealth) of children ages 6-17 years seen between 01/2016 and 03/2021 in a community-based primary healthcare network in California (n=77,298 patients). Study Outcomes: (1) # of primary care visits, (2) # of visits with ADHD diagnosis (ADHD-related visits), (3) # of first ADHD diagnoses, (4) # of PCP prescriptions for ADHD medications (stimulants, alpha-2 agonists, atomoxetine), (5) # of first PCP prescriptions of ADHD medications. Interrupted time-series analysis evaluated changes in rates of study outcomes during 4 quarters of the pandemic year (3/15/2020-3/15/2021) compared to pre-pandemic years. Patient demographic characteristics were compared pre-pandemic to pandemic year. Results: In the first quarter (Q1) of the pandemic year, all primary care visits dropped by 62% (CI 54.9-67.2%); ADHD-related visits dropped by 33% (95% CI 22.2-43.6%). In Q2-4, while all primary care visits remained significantly below pre-pandemic rates, ADHD-related visits returned to pre-pandemic rates. Conversely, rates of first ADHD diagnoses remained at half of pre-pandemic rates throughout the year (Q1-4). ADHD medication prescription rates remained stable throughout the pandemic year. The proportion of patients living in low-income neighborhoods who received ADHD-related care (ADHD-related visits and first ADHD diagnoses) were lower during the pandemic year compared to pre-pandemic years. Females comprised a higher proportion of first ADHD diagnoses compared to pre-pandemic years (34% vs. 28%, absolute standardized difference=0.13, p=0.03). Conclusion: Ongoing treatment for school-aged children with ADHD was maintained during the pandemic, especially in children from high-income families. Socioeconomic differences in ADHD-related care emphasize the need to improve access to care for all children with ADHD in the ongoing pandemic and beyond.

Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis

There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63–2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06–1.56), guanfacine (OR = 1.43, 95% CI = 1.12–1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09–1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.

Trends in Psychotropic Medication Prescriptions in Urban China From 2013 to 2017: National Population-Based Study

Purpose: Psychotropic medications are commonly used for treating mental disorders; however, there is currently no study on how commonly they are used in China. This study reported the trends in psychotropic medications prescriptions in urban China.Methods: A national population-based study was conducted using the China Health Insurance Research Association database to estimate the period prescription prevalence of 11 major classes of psychotropic medications annually during 2013–2017. The World Health Organization Anatomical Therapeutic Chemical (ATC) classification codes were used to identify psychotropic medications.Results: The prescription prevalence of any psychotropic medication increased from 8.110% (8.106–8.114%) in 2013 to 11.362% (11.357–11.366%) in 2017. The prescription prevalence of six classes increased significantly during 2013–2017, including sedatives-hypnotics (from 3.177 to 5.388%), anxiolytics (from 1.436 to 2.200%), antiepileptic drugs (from 1.416 to 2.140%), antipsychotics (from 0.809 to 1.156%), antidepressants (from 0.891 to 1.045%), and psycholeptic polypills (from 0.682 to 0.866%). The prescription prevalence of antidementia drugs increased from 0.069 to 0.122%, and mood stabilizers increased from 0.029 to 0.037%, although not statistically significant. The prescription prevalence of nootropic drugs, attention deficit hyperactivity disorder (ADHD) medications and drugs used in the treatment of addictive disorders was largely stable. Psychotropic medication prescription increased with age for all classes except for ADHD medications and mood stabilizers.Conclusion: Increasing trends in prescription prevalence were observed for most classes of psychotropic medications in urban China, although the prevalence was still lower than that in most developed countries. Further research is warranted to explore the potential treatment gap between China and most developed countries.

Current use of attention-deficit hyperactivity disorder (ADHD) medications and clinical characteristics of child and adolescent psychiatric outpatients prescribed multiple ADHD medications in Japan

Background/aim Patients with attention-deficit hyperactivity disorder (ADHD) manifest symptoms of hyperactivity, impulsivity, and/or inattention. ADHD medications available in Japan are limited compared with those in Western countries. Prescribing status has not been sufficiently evaluated in clinical settings in Japan. This study investigated the current use of ADHD medications and characteristics of patients who received multiple ADHD medications in a clinical setting in Japan. Methods Study participants were those who visited the Department of Child and Adolescent Psychiatry, Kohnodai Hospital between April 2015 and March 2020. We investigated patients who received osmotic-controlled release oral delivery system methylphenidate, atomoxetine, or guanfacine. A retrospective case–control design was used to evaluate the characteristics of patients who received multiple ADHD medications. Patients who were given three ADHD medications were defined as the case group. Randomly sampled sex- and age-matched patients diagnosed with ADHD were defined as the control group. We compared data for child-to-parent violence, antisocial behavior, suicide attempt or self-harm, abuse history, refusal to attend school, and two psychological rating scales (the ADHD-Rating Scale and Tokyo Autistic Behavior Scale). Results Among the 878 patients who were prescribed any ADHD medications, 43 (4.9%) received three ADHD medications. Logistic regression revealed that children with severe ADHD symptoms, autistic characteristics, or tendency of child-to-parent violence were more likely to have been prescribed three medications during their treatment. Conclusions Our findings suggest the approach to prevent the use of multiple ADHD medications. A prospective study to investigate the causality between prescribing status and clinical characteristics is warranted.

censusADHD Study: An Australian-wide medication-based recruitment study for Attention-Deficit/Hyperactivity Disorder

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) affects around 5% of children and is characterised by a persistent pattern of problems with focussing or maintaining attention and/or hyperactivity-impulsivity. The censusADHD Study is a richly-phenotyped nation-wide cohort of Australian children with ADHD that aims to examine the impact of children’s attention and behavioural problems on the financial, emotional, and psychological wellbeing of parents and caregivers. Methods: Families of potential ADHD cases aged between 6 and 11 years old were identified using Pharmaceutical Benefits Scheme (PBS) prescription records for ADHD medications held by the Department of Human Services and sent a study information letter. Data were collected from 1,574 primary caregivers via online survey from June-September 2015, including the behavioural profile of the index child, the child’s medication use and experiences with side-effects, and the impact of the child’s behaviour on the caregiver. Approximately 81% of caregivers also consented to record linkage of the child’s PBS and Medicare Benefits Schedule claims.Results: Boys were diagnosed with ADHD earlier (P=0.021) and more likely to present as the combined and predominantly hyperactive subtypes (P=0.001). Boys were also at higher risk for experiencing a school suspension (P&lt;0.001) or expulsion (P=0.043). Overall, children presenting as the combined subtype had higher rates of psychiatric comorbidities (P&lt;0.001). Finally, prescription costs for each family and the PBS significantly increased in the year following ADHD diagnosis (P&lt;0.001).Conclusion: Research examining the psychosocial and financial impact of ADHD on Australian children and their families in population-representative cohorts is needed. Our findings demonstrate the importance of examining both gender and ADHD subtype presentation in future studies.