Prescribed Attention-deficit/hyperactivity Disorder Medication Research Articles

Drug survival and risk factors for ADHD medication discontinuation in adults: A Danish Nationwide Registry-based cohort study.

Attention deficit hyperactivity disorder (ADHD) medication has proven effective for treating ADHD in adults, nonetheless previous studies have shown high rates of medication discontinuation. To assess drug survival and identify risk factors associated with discontinuation of ADHD medication. A nationwide registry-based cohort study in Danish adults who redeemed a prescription for ADHD medication for the first time between 2010 and 2015. All patients were followed for 5 years from the first redeemed prescription. Discontinuation was defined as a gap of 12 months between redemptions. Logistic regression analysis with odds ratio (OR) and Kaplan Meier analysis were used to examine risk factors (sex, age, socioeconomic status, substance use disorders, and comorbidities) associated with discontinuation. Twenty three thousand nine-hundred and sixteen patients with ADHD were identified. The 5-year overall drug survival was 29% in women vs. 23.5% in men. The risk of medication discontinuation was significantly higher in men compared to women, OR 1.26 (95% CI 1.19-1.34, p < 0.001). Adults aged 31-50 years had a significantly decreased risk of medication discontinuation compared to adults aged 18-30 years, OR 0.57 (95% CI 0.53-0.61, p < 0.001). Switching ADHD medication two times or three times or more significantly decreased the risk of discontinuation; OR 0.53 (95% CI 0.49-0.56, p < 0.001) and OR 0.26 (95% CI 0.23-0.30, p < 0.001), respectively. Substance use disorders and certain comorbidities were associated with medication discontinuation. Eating disorders, OR 0.71 (95% CI 0.64-0.78, p < 0.001), intellectual disabilities, OR 0.65 (95% CI 0.59-0.73, p < 0.001) and sleep disorders, OR 0.42 (95% CI 0.37-0.49, p < 0.001) were associated with continuation of ADHD medication. The 5-year overall drug survival was longer in women compared to men. Women with ADHD; adults aged 31-50; and patients with comorbid eating disorder; intellectual disability; sleep disorder and medication switching were individually associated with continuation of ADHD medication. Various factors were associated with medication discontinuation. Discontinuation should be acknowledged as a common phenomenon in patients with ADHD and calls for increased attention from the treatment responsible prescriber or team. Moreover, our findings suggest that timely, frequent medication switching, or temporary regimens may indeed represent optimal management strategies for a significant proportion of the ADHD population.

Attention-deficit/hyperactivity disorder and subsequent diagnoses of major psychiatric disorders: a nationwide population-based study.

We evaluated the risk of being diagnosed with various psychiatric disorders after an attention-deficit/hyperactivity disorder (ADHD) diagnosis using data from South Korea's National Health Insurance Service from 2002 to 2019, which covers approximately 97% of the country's population. ADHD and control groups were selected after propensity score matching was performed for individuals diagnosed with ADHD and their age- and sex-matched counterparts from the general population. Comorbid psychiatric disorders included depressive disorder, bipolar disorder, tic disorder, and schizophrenia. The incidence of newly diagnosed psychiatric disorders was compared between the groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and adjusted for ADHD medication prescription. After matching, 353,898 individuals were assigned to each of the two groups. Compared to the control group, the ADHD group showed a significantly higher risk of being subsequently diagnosed with depressive disorder, bipolar disorder, schizophrenia, and tic disorder. The onset age of depressive disorder, bipolar disorder, and schizophrenia in the ADHD group was 16-17 years, approximately 5 years earlier than that in the control group. The risk for depression was the highest in individuals with high income levels, and that for schizophrenia was the highest among rural patients. The median length of the follow-up time until the diagnosis of each comorbid psychiatric disorder was 7.53, 8.43, 8.53, and 8.34 years for depressive disorder, bipolar disorder, schizophrenia, and tic disorder, respectively. Individuals with ADHD had an overall higher risk of being diagnosed with subsequent psychiatric disorders than did the controls. Hence, they should be carefully screened for other psychiatric symptoms from an early age and followed up for an extended duration, along with appropriate interventions for ADHD symptoms, including psychosocial treatments and educational approaches.

Sex differences in attention-deficit hyperactivity disorder diagnosis and clinical care: a national study of population healthcare records in Wales.

Population-based studies have observed sex biases in the diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD). Females are less likely to be diagnosed or prescribed ADHD medication. This study uses national healthcare records, to investigate sex differences in diagnosis and clinical care in young people with ADHD, particularly regarding recognition and treatment of other mental health conditions. The cohort included individuals diagnosed with ADHD, born between 1989 and 2013 and living in Wales between 2000 and 2019. Routine primary and secondary healthcare record data were used to derive diagnoses of ADHD and other neurodevelopmental and mental health conditions, as well as ADHD and antidepressant medications. Demographic variables included ethnicity, socioeconomic deprivation and contact with social services. There were 16,458 individuals diagnosed with ADHD (20.3% females, ages 3-30 years), with a male-to-female ratio of 3.9:1. Higher ratios (4.8:1) were seen in individuals diagnosed younger (<12 years), with the lowest ratio (1.9:1) in those diagnosed as adults (>18). Males were younger at first recorded ADHD diagnosis (mean = 10.9 vs. 12.6 years), more likely to be prescribed ADHD medication and younger at diagnosis of co-occurring neurodevelopmental conditions. In contrast, females were more likely to receive a diagnosis of anxiety, depression or another mental health condition and to be prescribed antidepressant medications, prior to ADHD diagnosis. These sex differences were largely stable across demographic groups. This study adds to the evidence base that females with ADHD are experiencing later recognition and treatment of ADHD. The results indicate that this may be partly because of diagnostic overshadowing from other mental health conditions, such as anxiety and depression, or initial misdiagnosis. Further research and dissemination of findings to the public are needed to improve awareness, timely diagnosis and treatment of ADHD in females.

Systematic review and meta-analysis:relative age in attention-deficit/ hyperactivity disorder and autism spectrum disorder.

Youngest students in their class, with birthdates just before the school entry cut-off date, are overrepresented among children receiving an Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosis or medication for this. This is known as the relative age effect. This systematic review and meta-analysis summarises the evidence on the influence of relative age on ADHD symptoms, diagnosis and medication prescribing. As no review to date has investigated the association with autism spectrum disorder (ASD) diagnosis, this is also examined. Following prospective registration with PROSPERO, we conducted a systematic review according to the PRISMA guidelines. We searched seven databases: Medline, Embase, PsycInfo, Web of Science Core Collection, ERIC, Psychology and Behavioural Sciences Collection, and Cochrane Library. Additional references were identified from manual search of retrieved reviews. We performed a meta-analysis of quantitative data. Thirty-two studies were included, thirty-one investigated ADHD and two ASD. Younger relative age was associated with ADHD diagnosis and medication, with relative risks of 1.38 (1.36-1.52 95% CI) and 1.28 (1.21-1.36 95% CI) respectively. However, risk estimates exhibited high heterogeneity. A relative age effect was observed for teacher ratings of ADHD symptoms but not for parent ratings. With regard to ASD, the youngest children in their school year were more likely to be diagnosed with ASD. This review confirms a relative age effect for ADHD diagnosis and prescribed ADHD medication and suggests that differences in teacher and parent ratings might contribute to this. Further research is needed on the possible association with ASD.

Childhood attention-deficit hyperactivity disorder: socioeconomic inequalities in symptoms, impact, diagnosis and medication.

Children from disadvantaged backgrounds are at greater risk of attention-deficit hyperactivity disorder (ADHD)-related symptoms, being diagnosed with ADHD, and being prescribed ADHD medications. We aimed to examine how inequalities manifest across the 'patient journey', from perceptions of impacts of ADHD symptoms on daily life, to the propensity to seek and receive a diagnosis and treatment. We investigated four 'stages': (1) symptoms, (2) caregiver perception of impact, (3) diagnosis and (4) medication, in two data sets: UK Millennium Cohort Study (MCS, analyticn ~ 9,000), with relevant (parent-reported) information on all four stages (until 14 years); and a population-wide 'administrative cohort', which includes symptoms (child health checks) and prescriptions (dispensing records), born in Scotland, 2010-2012 (analytic n ~ 100,000), until ~6 years. We described inequalities according to maternal occupational status, with percentages and relative indices of inequality (RII). The prevalence of ADHD symptoms and medication receipt was considerably higher in the least compared to the most advantaged children in the administrative cohort (RIIs of 5.9 [5.5-6.4] and 8.1 [4.2-15.6]) and the MCS (3.08 [2.68-3.55], 3.75 [2.21-6.36]). MCS analyses highlighted complexities between these two stages, however, those from least advantaged backgrounds, with ADHD symptoms, were the least likely to perceive impacts on daily life (15.7% vs. average 19.5%) and to progress from diagnosis to medication (44.1% vs. average 72.5%). Despite large inequalities in ADHD symptoms and medication, parents from the least advantaged backgrounds were less likely to report impacts of ADHD symptoms on daily life, and their children were less likely to have received medication postdiagnosis, highlighting how patient journeys differed according to socioeconomic circumstances.

Attention-Deficit Hyperactivity Disorder (ADHD) Medication Use Trajectories Among Women in the Perinatal Period.

An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use for women in the perinatal period have not been well described. This study aimed to describe ADHD medication use patterns from 1year before pregnancy to 1year after delivery, and to describe sociodemographic characteristics and clinical features by medication trajectories. The population-based cohort study included pregnancies in Denmark between 1997 and 2020, from the Medical Birth Register, by women who filled at least one prescription for ADHD medication from 12 months before pregnancy until 12 months after delivery. We applied group-based trajectory modeling to classify women into subgroups based on the identification of heterogeneous ADHD medication treatment patterns, and described the characteristics associated with these groups. Overall, we included 4717 pregnancies leading to liveborn singletons by 4052 mothers with a mean (standard deviation) age of 27.5 (5.6) years. We identified four treatment trajectories across pregnancy and the postpartum period: continuers (23.3%), discontinuers (41.8%), interrupters who ceased filling prescriptions during pregnancy but resumed postpartum (17.2%), and postpartum initiators (17.7%). Continuers were older at the time of conception, gave birth in more recent years, were more likely to smoke during pregnancy, and used other psychotropic medications during pregnancy. A large proportion of continuers used methylphenidate (89.1%) compared with the other groups (75.9-84.1%) and had switched ADHD medication type during the whole period (16.4% vs. 7.4-14.8%). We found that approximately 60% of women discontinued or interrupted their ADHD medication around pregnancy, and those who continued differed in sociodemographic and clinical factors that may reflect more severe ADHD.

Descriptive analysis of poisoning cases involving attention deficit hyperactivity disorder medications in Hong Kong.

The number of poisoning cases involving attention deficit hyperactivity disorder (ADHD) medications has reportedly risen with their increased use. However, there is limited relevant evidence from Asia. We analysed the characteristics of poisoning events involving these medications in Hong Kong. We retrieved data regarding ADHD medication-related poisoning cases from the Hong Kong Poison Information Centre and conducted a descriptive analysis of the demographic information and poisoning information including sources of cases, exposure reason, exposure location, and outcome. The HKPIC data were linked with the Hospital Authority Clinical Data Analysis and Reporting System (CDARS) via de-identified Accident and Emergency numbers of public hospitals to investigate clinical characteristics. We also retrieved ADHD medication prescription records from the CDARS, then compared trends between poisoning cases and ADHD medication use. We identified 72 poisoning cases involving ADHD medications between 2009 and 2019, of which approximately 70% occurred in the affected individual's residence; most were intentional poisoning events (65.3%). No statistically significant association was observed between ADHD medication prescription trends and poisoning events involving ADHD medications. Of the 66 cases (91.7%) successfully linked to CDARS, 40 (60.6%) occurred in individuals with ADHD (median age: 14 years); 26 (39.4%) occurred in individuals who lacked ADHD (median age: 33 years) but displayed higher rates of other mental disorders including depression and anxiety. No significant correlation was evident between ADHD medication prescriptions and poisoning events involving ADHD medications. However, medication management and caregiver education must be emphasised to prevent potential poisoning events.

Association of Prenatal Exposure to Benzodiazepines and Z-Hypnotics With Risk of Attention-Deficit/Hyperactivity Disorder in Childhood

Evidence is limited regarding the safety of prenatal benzodiazepine and z-hypnotic exposure and its association with long-term neurodevelopment in childhood. To quantify the associations of the timing and number of intervals of prenatal exposure to benzodiazepines and/or z-hypnotics with the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood. This cohort study used data from the 1999 to 2008 population-based Norwegian Mother, Father and Child Cohort Study, which are linked to the Medical Birth Registry of Norway, Norwegian Patient Registry, and Norwegian Prescription Database. Two populations of participants were created: a full sample and a mental health sample. The full sample included mothers and their live-born singletons, whereas the mental health sample was restricted to offspring of mothers who reported anxiety, depression, or sleeping problems during pregnancy or 6 months before pregnancy. Data were analyzed from September 2021 to February 2022. Maternal self-report of benzodiazepine and/or z-hypnotic use during pregnancy was grouped into early pregnancy exposure and middle and/or late pregnancy exposure for analysis of the association with timing of exposure, and number of 4-week intervals of exposure was classified (single [1] vs multiple [≥2]) for analysis of the association with number of exposed intervals. The outcome was ADHD, defined as time to ADHD diagnosis or filled prescription for ADHD medication. To control for confounding, inverse probability of treatment-weighted Cox proportional hazards regression models were used. Hazard ratios and 95% CIs were estimated. The weights were derived from propensity score modeling of the probability of benzodiazepine and/or z-hypnotic exposure as a function of potential confounders between the exposure and the outcome, including maternal symptoms of depression and anxiety. The full sample comprised 82 201 pregnancies, and the mental health sample included 19 585 pregnancies. In total, 681 offspring (0.8%) in the full sample and 468 offspring (2.4%) in the mental health sample were prenatally exposed to benzodiazepines and/or z-hypnotics. After weighting, exposure in early (hazard ratio, 0.74; 95% CI, 0.39-1.94) and middle and/or late (hazard ratio, 0.76; 95% CI, 0.35-1.61) pregnancy was not associated with increased risk of childhood ADHD. There was no evidence of substantial association between the number of exposed intervals during pregnancy and childhood ADHD. Results of this study suggest that there may be no increased risk of childhood ADHD associated with prenatal exposure to benzodiazepines and/or z-hypnotics, regardless of timing of exposure and number of exposed intervals. However, these findings should be interpreted with caution due to low study power.

Pediatric Off-label Antipsychotic Use for Attention-Deficit/Hyperactivity Disorder

PurposeOff-label antipsychotic use for behavioral symptoms in pediatric attention-deficit/hyperactivity disorder (ADHD) poses safety concerns, and evidence to support such use is limited. This study aims to investigate the risk of off-label antipsychotic use associated with comorbid disruptive behavior disorder (DBD) among a cohort of youth with ADHD. MethodsA cohort study was conducted using IQVIA PharMetrics Plus for Academics data from 2007 to 2020. Youth 5 to 15 years of age at the index ADHD visit were included in the cohort. The index ADHD visit meets at least 1 of the following criteria: (1) 1 inpatient ADHD visit, (2) 2 outpatient ADHD visits within 90 days, or (3) an ADHD medication prescription fill within 30 days of an outpatient ADHD visit. We excluded youth who had a diagnosis of DBD or a US Food and Drug Administration (FDA)–approved indication for antipsychotics at baseline. Youth were followed up until antipsychotic initiation or were censored at a loss of coverage, receipt of an FDA-indicated diagnosis, or end of the study. A Cox proportional hazards regression model with DBD as a time-varying covariate estimated the hazard of antipsychotic use after the index ADHD visit. FindingsOf 41,098 youth with ADHD who met the study criteria, 4557 were diagnosed with DBD during follow-up. The incidence of antipsychotic initiation was 19.6 (95% CI, 18.7– 20.5) per 1000 person-years. After adjustment for baseline covariates, the hazard ratio of antipsychotic initiation associated with DBD was 4.64 (95% CI, 4.15–5.18). ImplicationsAntipsychotic use among youth with ADHD is more likely in the presence of DBD, suggesting that an off-label use is for behavior problems.

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

The aim of this study was to assess rates of primary care provider (PCP) diagnosis and treatment of school-age children with attention-deficit/hyperactivity disorder (ADHD) during the COVID-19 pandemic compared with prepandemic years and to investigate disparities in care. We retrospectively analyzed electronic health records from all primary care visits (in-person and telehealth) of children aged 6 to 17 years seen between January 2016 and March 2021 in a community-based primary health care network (n = 77,298 patients). Study outcomes are as follows: (1) number of primary care visits, (2) number of visits with ADHD diagnosis (ADHD-related visits), (3) number of PCP prescriptions for ADHD medications, (4) number of patients with first ADHD diagnoses, and (5) number 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 (March 15, 2020-March 15, 2021) compared with prepandemic years (January 1, 2016-March 14, 2020). Patient demographic characteristics during prepandemic and pandemic years were compared. ADHD-related visits dropped in the first quarter of the pandemic year by 33% (95% confidence interval, 22.2%-43.6%), returning to prepandemic rates in subsequent quarters. ADHD medication prescription rates remained stable throughout the pandemic year. Conversely, rates of first ADHD diagnoses and first medication prescriptions remained significantly lower than prepandemic rates. The proportion of ADHD-related visits for patients living in low-income neighborhoods was lower in the pandemic year compared with prepandemic years. Ongoing treatment for school-age children with ADHD was maintained during the pandemic, especially in 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.

Association of Perinatal and Childhood Ischemic Stroke With Attention-Deficit/Hyperactivity Disorder

Early detection of attention-deficit/hyperactivity disorder (ADHD) plays a crucial role in reducing negative effects on everyday life, including academic failure and poor social functioning. Children who survive ischemic strokes risk major disabilities, but their risk of ADHD has not been studied in nationwide cohorts. To assess the risk of ADHD in children after pediatric ischemic stroke. Participants in this Swedish nationwide cohort study included 1320 children diagnosed with ischemic stroke recorded in linked Swedish national registers from January 1, 1969, to December 31, 2016, without prior ADHD diagnosis. Ten matched controls were identified for each index case, and first-degree relatives were identified for index individuals and controls. Analyses were stratified by perinatal and childhood strokes and presence of comorbid adverse motor outcomes and/or epilepsy. End of follow-up was the date of ADHD diagnosis, death, or December 31, 2016, whichever occurred first. Data analyses were performed August 1 to 28, 2021. Pediatric ischemic stroke. Attention-deficit/hyperactivity disorder identified using codes from the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and/or prescribed ADHD medication recorded in the Medical Birth Register, National Patient Register, or Prescribed Drug Register after stroke. Cox proportional hazards regression was used to assess adjusted hazard ratios (aHRs) for ADHD after pediatric stroke, adjusting for parental age and ADHD in first-degree relatives. Of 1320 children with stroke included in the analysis (701 boys [53.1%]), 75 (45 boys [60.0%]) were diagnosed with ADHD after stroke compared with 376 (252 boys [67.0%]) among the controls (aHR, 2.00 [95% CI, 1.54-2.60]). The risk was increased after both perinatal (aHR, 2.75 [95% CI ,1.65-4.60]) and childhood (aHR, 1.82 [95% CI, 1.34-2.48]) strokes and were similar if children born preterm or small for gestational age were excluded. Compared with controls, risks of ADHD were higher among children with perinatal stroke and adverse motor outcomes and/or epilepsy (aHR, 6.17 [95% CI, 2.80-13.62]) than among those without these comorbidities (aHR, 1.65 [95% CI, 0.80-3.42]). However, findings were similar in childhood stroke for children with adverse motor outcomes and/or epilepsy (aHR, 1.80 [95% CI, 1.12-2.89]) and among those without these comorbidities (aHR, 1.92 [95% CI, 1.28-2.90]). This cohort study of 1320 children with pediatric ischemic stroke suggests that there is an increased risk of ADHD, particularly in children with adverse motor outcomes and/or epilepsy, compared with controls. The risk increases after childhood strokes regardless of comorbidities.

Predictors of Stimulant Medication Continuity in Children with Attention-Deficit/Hyperactivity Disorder.

The objective of this study was to examine the simultaneous impact of patient-related and parent-related factors, medication-related factors, and health care system-related factors on attention-deficit/hyperactivity disorder (ADHD) medication continuity. Stimulant-naïve children (N = 144, M age = 8 yrs, 71% male) with ADHD completed a methylphenidate (MPH) trial and were followed for 1 year after trial completion and return to community care. Multivariable analysis investigated predictors of (1) having at least 1 filled ADHD prescription after return to community care versus none and (2) having more days covered with medicine after return to community care. Predictors included race; age; sex; income; baseline ADHD symptom severity; MPH trial experience; child and parent mental health conditions; and parent beliefs about ADHD, ADHD medications, and therapeutic alliance. One hundred twenty-one children (84%) had at least 1 filled ADHD medication prescription (mean = 178 d covered by medication) in the year after return to community care. Multivariable models found that a weaker perceived clinician-family working alliance predicted not filling any ADHD prescriptions. Among those who filled ≥1 prescription, factors linked to fewer days of ADHD medication coverage included child sociodemographic factors (non-White race, older age, being female, and lower income), lower parent beliefs that the child's ADHD affects their lives, and higher parent beliefs that medication is harmful, while child oppositional defiant disorder and parental ADHD predicted having more days of medication coverage. Child demographic factors, parent beliefs, and medication-related factors are associated with continuation of ADHD medication. These findings may facilitate the development of effective strategies to improve ADHD medication continuity for children from diverse groups.

Antenatal corticosteroid administration and attention-deficit/hyperactivity disorder in childhood: a regression discontinuity study.

Background:Antenatal corticosteroids reduce respiratory morbidity in preterm infants, but their use during late preterm gestation (34–36 weeks) is limited because their safety for longer-term child neurodevelopment is unclear. We sought to determine if fetuses with higher probability of exposure to antenatal corticosteroids had increased rates of prescriptions for attention-deficit/hyperactivity disorder (ADHD) medication in childhood, using a quasiexperimental design that better controls for confounding than existing observational studies.Methods:We identified 16 358 children whose birthing parents were admitted for delivery between 31 + 0 (31 weeks, 0 days) and 36 + 6 weeks’ gestation in 2000–2013, using a perinatal data registry from British Columbia, Canada, and linked their records with population-based child ADHD medication data (2000–2018). We used a regression discontinuity design to capitalize on the fact that pregnancies presenting for delivery immediately before and immediately after the clinical cut-off for antenatal corticosteroid administration of 34 + 0 weeks’ gestation have very different levels of exposure to corticosteroids, but are otherwise similar with respect to confounders.Results:Over a median follow-up period of 9 years, 892 (5.5%) children had 1 or more dispensations of ADHD medication. Children whose birthing parents were admitted for delivery just before the corticosteroid clinical cut-off of 34 + 0 weeks’ gestation did not appear to be more likely to be prescribed ADHD medication than those admitted just after the cut-off (rate ratio 1.1, 95% confidence interval [CI] 0.8 to 1.6; 1.3 excess cases per 100 children, 95% CI −2.5 to 5.7).Interpretation:We found little evidence that children with higher probability of exposure to antenatal corticosteroids have higher rates of ADHD prescriptions in childhood, supporting the safety of antenatal corticosteroids for this neurodevelopmental outcome.

Association of Timing and Duration of Prenatal Analgesic Opioid Exposure With Attention-Deficit/Hyperactivity Disorder in Children

Prior studies have reported that the use of illicit opioids during pregnancy is associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring; however, evidence regarding the association of analgesic opioids is limited. To examine the association of timing and duration of prenatal analgesic opioid exposure with ADHD in children. This cohort study uses data from the Norwegian Mother, Father and Child Cohort study (1999-2008), a nationwide birth cohort study linked to national health registries, with a mean (SD) follow-up of 10.8 (2.2) years. A total of 73 784 live-born singleton children born to 62 013 mothers who reported a pain-related condition before and/or during pregnancy were included, with 2 comparator groups: (1) mothers who did not use any opioids and (2) mothers who used opioids before pregnancy only. Data were analyzed from June to December 2020. Maternal self-report of analgesic opioid use during pregnancy, by timing (early and middle and/or late) and duration (≥5 weeks vs ≤4 weeks). Diagnosis of ADHD or filled prescription for ADHD medication in children and symptoms of ADHD at child age 5 years, measured by Conners' Parent Rating Scale-Revised. Inverse probability of treatment weights were used to control for measured confounding. Cox regression was used to estimate hazard ratios (HRs) and 95% CIs. The analyses of ADHD diagnosis and ADHD symptoms included 73 480 children (35 996 [49.0%] girls; mean [SD] maternal age, 30.0 [4.6] years) and 31 270 children (15 377 [49.2%] girls; mean [SD] maternal age, 30.5 [4.4] years), respectively. Overall, 1726 children in the ADHD diagnosis sample (2.3%) and 667 children in the ADHD symptom sample (2.1%) were exposed to an analgesic opioid at least once during gestation. No associations between timing of prenatal analgesic opioid exposure and ADHD diagnosis or symptoms was found. Exposure for 5 or more weeks was associated with an increased risk of ADHD diagnosis (HR, 1.60, 95% CI, 1.04-2.47) compared with exposure for 4 weeks or less; however, there was no such association for the risk of ADHD symptoms. In this cohort study, a slightly elevated risk of ADHD diagnosis after prenatal analgesic opioid exposure for 5 or more weeks was found compared with exposure for 4 weeks or less. This result may be driven by longer duration of use; however, the role of residual or unmeasured confounding cannot be excluded. This finding needs to be replicated in other studies.

Treatment with Methylphenidate for Attention Deficit Hyperactivity Disorder (ADHD) and the Risk of All-Cause Poisoning in Children and Adolescents: A Self-Controlled Case Series Study.

BackgroundChildren and adolescents with attention deficit hyperactivity disorder (ADHD) are at higher risk of all-cause poisoning by drugs and chemicals (intentional or accidental). Currently, there is limited data on whether medication treatment for ADHD can reduce the risk of all-cause poisoning.MethodsPatients aged 5–18 years with a methylphenidate (MPH) prescription and an incident poisoning diagnosis between January 2001 and June 2020 were identified from the Hong Kong Clinical Data Analysis and Reporting System. A self-controlled case series study design was used to compare the incidence rate ratios (IRRs) of all-cause poisoning during different risk windows (30 days before the first MPH prescription, exposure periods within 30 days of the first prescription, and periods of subsequent exposure) compared with the reference window (other non-exposure periods).Results42,203 patients were prescribed ADHD medication in Hong Kong during the study period. Of these, 417 patients who had both an MPH prescription and poisoning incident recorded were included in the main analysis. Compared with other non-exposed periods, a higher risk of poisoning was found in the 30 days before the first prescription (IRR 2.64, 95% confidence interval [CI] 1.33–5.22) and exposure periods within 30 days of the first prescription (IRR 2.18, 95% CI 1.06–4.48), but not during prolonged exposure. However, compared with 30 days before the first prescription as well as exposure periods within 30 days of the first prescription, there was a lower risk during the subsequent exposure (IRRs 0.49 and 0.60, respectively). Similar results to the main analysis were also found in the subgroup analysis of intentional poisoning and females, but not in that of accidental poisoning and males.ConclusionsThe risk of all-cause poisoning was higher shortly before and after the first MPH prescription and became lower during the subsequent prescription period. Our results do not support an association between the use of MPH and an increased risk of all-cause poisoning in children and adolescents and, in fact, suggest that longer-term use of MPH may be associated with a lower risk of all-cause poisoning, although this latter finding requires further study.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-021-00824-x.

Medications for attention-deficit/hyperactivity disorder in Japan: A retrospective cohort study of label compliance.

AimTo assess label compliance in prescription of medications approved for treatment of attention‐deficit/hyperactivity disorder (ADHD) in Japan at the time of this study: methylphenidate (MPH), atomoxetine, and guanfacine.MethodsRetrospective descriptive study was conducted in prevalent‐user cohorts from the Japan Medical Data Center database. Patients who were prescribed a study drug between January 1, 2013 and September 30, 2018 and were in the database for ≥30 days were included. A prescription was considered compliant if all 4 criteria were satisfied: appropriate age, daily dose not exceeding the approved maximum, no contraindicated concurrent medications, and no contraindicated conditions.ResultsAmong 17 418 patients who were prescribed a study drug during 2013‐2018, 73% were male and 53% were children (aged <18 years). Fewer than 2% of prescriptions were for patients outside the approved age, 10%‐13% of patients in the atomoxetine and MPH cohorts received ≥1 prescription exceeding maximum approved dose, no patients were co‐prescribed a contraindicated medication, and 16%–18% of patients in the MPH cohorts had ≥1 contraindicated condition. During their first 500 days of use, for approximately 73%‐86% of patients, all prescriptions were compliant with all label requirements.ConclusionsAmong patients exposed to ADHD medications in Japan during 2013‐2018, nearly all prescriptions for these medications were label‐compliant for age. For >85% of patients, all prescriptions were label‐compliant for dose, and for approximately 80%, all prescriptions were label‐compliant for contraindicated conditions. We did not find evidence of widespread abuse or noncompliant use of prescribed ADHD medications.

Attention-deficit/hyperactivity disorder in children following prenatal exposure to antidepressants: results from the Norwegian mother, father and child cohort study.

To determine the association between child attention-deficit/hyperactivity disorder (ADHD) and prenatal exposure to selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor antidepressants, by timing and duration, with quantification of bias due to exposure misclassification. Norwegian Mother, Father and Child Cohort Study and national health registries. Nationwide, Norway. A total of 6395 children born to women who reported depression/anxiety in pregnancy and were either medicated with SSRI/SNRI in pregnancy (n=818) or non-medicated (n=5228), or did not report depression/anxiety but used antidepressants 6months before pregnancy (discontinuers, n=349). Diagnosis of ADHD or filled prescription for ADHD medication in children, and mother-reported symptoms of ADHD by child age 5years. When the hazard was averaged over the duration of the study follow up, there was no difference in ADHD risk between ever in utero SSRI/SNRI-exposed children and comparators (weighted hazard ratio [wHR] 1.07, 95% CI 0.76-1.51 versus non-medicated; wHR 1.53, 95% CI 0.77-3.07 versus discontinuers). Underestimation of effects due to exposure misclassification was modest. In early childhood, the risk for ADHD was lower with prenatal SSRI/SNRI exposure compared with no exposure, and so were ADHD symptoms (weighted β -0.23, 95% CI -0.39 to -0.08); this risk became elevated at child age 7-9years (wHR 1.93, 95% CI 1.22-3.05). Maternal depression/anxiety before pregnancy was independently associated with child ADHD. Prenatal SSRI/SNRI exposure is unlikely to considerably increase the risk of child ADHD beyond that posed by maternal depression/anxiety. The elevated risk at child age 7-9years needs to be elucidated. Women with depression who use antidepressants in pregnancy do not have greater risk of having children with ADHD. Findings in school-age children needs follow up.

Audit of ADHD medication prescription and monitoring in intellectual disability services, Greater Glasgow &amp; Clyde

AimsStudies have shown that people with intellectual disability (ID) show a greater severity of attention deficit hyperactivity disorder (ADHD) symptoms and atypical presentation, as well as having a greater risk of developing comorbidities, such as challenging behaviour, anxiety, tic disorders and sleep problems. It is estimated that 1.5% of patients with ID will have a clinical diagnosis of ADHD.The aim of this audit was to find whether individuals with ID and ADHD, who are prescribed medication for ADHD are adequately monitored and reviewed in accordance with the ADHD medication prescription guidance by NICE and the Royal College of Psychiatrists (RCPsych).MethodThis audit looked at ADHD medication prescription for the ID population within Greater Glasgow &amp; Clyde NHS. This is the 6th audit cycle where electronic records (EMIS) were analysed between 28/9/19 to 09/10/20. (The 5th cycle data collection period ended on 28/9/19). We collected data on all patients aged over 18 years.An audit tool was developed to find whether the following were documented; patient demographics, physical health monitoring, symptom severity, medication dosage, side effects, need for ongoing treatment and frequency of review. 100% of patients should have all components on the ADHD audit tool documented, as per NICE/ RCPsych prescription guidance.Result32 patients were identified as being diagnosed with ADHD prescribed medication. One patient was impacted by the COVID-19 pandemic which meant that the required monitoring was not fully carried out. The age ranged from 18 to 56 years. 75% had mild intellectual disability, 19% had moderate and 6% had severe, with no cases of profound intellectual disability. Blood Pressure/pulse was recorded in 84% of patients. Height/weight/ BMI was recorded in 81% of patients. 97% of patients had ADHD symptom severity, medication dosage, side effects, need for ongoing treatment and frequency of review recorded.ConclusionThere is further scope for improvement in the monitoring and documentation of physical health observations, however there was a significant improvement compared to the previous cycle of the audit. Other aspects of monitoring and documentation appear to be recorded in almost 100% of patients. This finding emphasises the challenges of physical health monitoring and compliance in psychiatry as a whole. We need to continue to encourage awareness and education around the physical health risks to our patients, not only due to their comorbidities but also as a result of the psychotropic medications we prescribe them.

Effect of relative age on childhood mental health: A cohort of 9,548,393 children and adolescents.

The effect of relative age on the diagnoses of attention deficit hyperactivity disorder (ADHD), disruptive behavior disorder (DD), anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications remains unclear. To clarify the impact of relative age in a school year with the diagnoses of ADHD, DD, anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications. The annual cutoff birthdate for entry to school in Taiwan is August 31. The Taiwan National Health Insurance Research Database was used to enroll 9,548,393 children and adolescents aged 3-17years during the study period (September 1, 2001, to August 31, 2011). The Poisson regression model was performed to examine the likelihood of receiving diagnoses of ADHD, DD, anxiety disorder, and depressive disorder, as well as the prescription of ADHD and antidepressant medications among children born in August (the youngest) and September (the oldest). Both boys and girls born in August had a higher risk of being diagnosed as having ADHD (odds ratio [OR]=boys: 1.65, girls: 1.80), DD (1.29, 1.45), anxiety disorder (1.49, 1.33), and depressive disorder (1.10, 1.10). Furthermore, children born in August were more likely to be prescribed ADHD medication (1.71, 1.72) and antidepressants (1.18, 1.09) compared with those born in September. Relative age, as an indicator of neurocognitive maturity, is a critical factor for the likelihood of being diagnosed as having ADHD, DD, anxiety disorder, and depressive disorder among children and adolescents.

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.