Placebo-related improvement with methylphenidate treatment in children with ADHD.

Non-specific effects of methylphenidate treatment, including expectancy and regression to the mean effects, contribute to the overall effect of methylphenidate on attention-deficit/hyperactivity disorder (ADHD) symptoms. Knowledge on the extent to which non-specific effects contribute to the overall effect and whether regression to the mean explains part of the non-specific effects, is currently lacking. A double-blind, randomized, placebo-controlled, cross-over trial was used to compare parent and teacher ratings of child ADHD symptoms at baseline and during treatment with placebo and 5, 10, 15 and 20 mg of methylphenidate, twice daily. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). The extent to which non-specific effects contributed to the effects of methylphenidate was determined by ADHD symptom reductions observed with placebo versus reductions observed with active doses of methylphenidate. The influence of regression to the mean was examined by estimating the contribution of baseline ADHD symptom severity to the effects observed with placebo treatment. Data were analyzed using multilevel analyses. We observed significant non-specific effects of methylphenidate for parent-rated ADHD symptoms, but not for teacher-rated symptoms. For parent reported hyperactive/impulsive symptoms, higher baseline symptoms predicted larger effects with placebo, indicating regression to the mean effects. For parent-reports, a significant part of the overall effect of methylphenidate treatment is explained by non-specific effects. Our findings stress the importance of taking non-specific effects into account when evaluating methylphenidate treatment, by including teacher-reports and using a double baseline assessment during titration. Comparing active medication with a placebo in the titration trial has the potential to identify non-specific effects.

Practice Pearls for Stimulant Treatment of Attention-Deficit/Hyperactivity Disorder in Youth.

Over half of youth with attention-deficit/hyperactivity disorder (ADHD) have co-occurring psychiatric or medical conditions that present treatment challenges. Stimulants are the most effective pharmacologic treatment of ADHD for preschoolers to adults but questions about safety with co-occurring conditions frequently arise. In addition, stigma surrounding diagnosis and treatment can negatively impact care. This manuscript presents evidence-based practice pearls to guide treatment decisions for youth with ADHD and common coexisting psychiatric and medical conditions. Recommendations address specific stimulant adverse effects (i.e., anxiety, cardiac, growth, mania, psychosis) along with management strategies. Pearls were developed for the most common clinical questions, controversial topics, or therapeutic issues that may not be widely known. The goals of this manuscript are to: 1) provide a detailed resource for interprofessional teams regarding stimulant use in youth with ADHD, 2) improve therapeutic outcomes for youth with ADHD and co-occurring psychiatric and/or medical conditions through evidence-based recommendations, and 3) decrease stigma associated with stimulant use through education.

Attention-deficit hyperactivity disorder and psychostimulant use in patients seeking dental care-Associations with common orofacial pain complaints.

BACKGROUND: Dental medicine should expand its scope to properly assess medical and psychosocial factors that might have an impact on patients' oral health. Based on previous literature and clinical experience, attention-deficit/hyperactivity disorder and psychostimulant medications might represent factors associated with orofacial pain symptoms. OBJECTIVE: The aim of the study was to assess whether common orofacial pain complaints such as jaw pain, jaw clicking, teeth clenching and headaches are more prevalent in dental patients who have an ADHD diagnosis and/or use psychostimulant medications. METHODS: Orofacial pain symptoms prevalence was compared among four groups from a sample of new patients seeking dental care at Tufts University School of Dental Medicine (n = 11 699) based on ADHD diagnosis and psychostimulants intake: G1: no ADHD, no stimulants; G2: yes ADHD, yes stimulants; G3: yes ADHD, no stimulants; G4: no ADHD, yes stimulants. RESULTS: In multivariable logistic regression models adjusting for age, gender, tobacco use, and alcohol consumption, significant differences were found for clenching (p < .0001), jaw pain (p < .0001), and headache (p < .0001). Compared to G1, two groups (G2 and G4) exhibited significantly higher odds of clenching and headaches, whereas only G2 exhibited significantly higher odds of jaw pain. CONCLUSIONS: In comparison with patients without ADHD and not taking psychostimulants medications, dental patients using psychostimulants with and without ADHD diagnosis report headaches and teeth clenching more frequently, while jaw pain is reported more frequently only by those taking psychostimulants with an ADHD diagnosis. Further research is necessary to assess the nature of these associations and their clinical relevance.

Stimulant use and opioid-related harm in patients on long-term opioids for chronic pain.

BACKGROUND: There is lack of clarity regarding the impact of and optimal clinical response to stimulant use among people prescribed long-term opioid therapy (LTOT) for pain. OBJECTIVE: To determine if a positive urine drug test (UDT) for stimulants was associated with subsequent opioid-related harm or discontinuation of LTOT. DESIGN: Retrospective cohort study. PATIENTS: People living with and without HIV living in a major metropolitan area with public insurance, prescribed LTOT for chronic, non-cancer pain (n=600). MAIN MEASURES: UDT results from January 2012 to June 2019 were evaluated against 1) opioid-related emergency department (ED) visits (oversedation, constipation, infections associated with injecting opioids, and opioid seeking) or death in each 90-day period following a UDT, using logistic regression, and 2) LTOT discontinuation. RESULTS: There were no opioid overdose deaths within 90 days following a stimulant-positive UDT. A stimulant-positive UDT was not statistically significantly associated with opioid-related ED visits within 90 days (adjusted odds ratio [aOR] 1.39; 95% CI=0.88-2.21). Stimulant-positive UDT was independently associated with subsequent discontinuation of LTOT within 90 days (aOR 2.96; 95% CI=2.13 - 4.12). Living with HIV was independently associated with decreased odds of LTOT discontinuation (aOR 0.65; 95% CI 0.43 - 0.99). CONCLUSIONS: Despite no association between a stimulant-positive UDT and subsequent opioid-related harm, there was an association with subsequent LTOT discontinuation, with heterogeneity across clinical groups. Detection of stimulant use should result in a discussion of substance use and risk, rather than reflex LTOT discontinuation.

Impact of COVID-19 pandemic on prescription stimulant use among children and youth: a population-based study.

COVID-19 associated public health measures and school closures exacerbated symptoms in some children and youth with attention-deficit hyperactivity disorder (ADHD). Less well understood is how the pandemic influenced patterns of prescription stimulant use. We conducted a population-based study of stimulant dispensing to children and youth ≤ 24 years old between January 1, 2013, and June 30, 2022. We used structural break analyses to identify the pandemic month(s) when changes in the dispensing of stimulants occurred. We used interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected stimulant use. Our main outcome was the change in the monthly rate of stimulant use per 100,000 children and youth. Following an initial immediate decline of 60.1 individuals per 100,000 (95% confidence interval [CI] - 99.0 to - 21.2), the monthly rate of stimulant dispensing increased by 11.8 individuals per 100,000 (95% CI 10.0-13.6), with the greatest increases in trend observed among females, individuals in the highest income neighbourhoods, and those aged 20 to 24. Observed rates were between 3.9% (95% CI 1.7-6.2%) and 36.9% (95% CI 34.3-39.5%) higher than predicted among females from June 2020 onward and between 7.1% (95% CI 4.2-10.0%) and 50.7% (95% CI 47.0-54.4%) higher than expected among individuals aged 20-24 from May 2020 onward. Additional research is needed to ascertain the appropriateness of stimulant use and to develop strategies supporting children and youth with ADHD during future periods of long-term stressors.

Methylphenidate use and restorative treatment needs in young adults with attention deficit hyperactivity disorder.

OBJECTIVE: To assess the effect and dose-response of methylphenidate (MP) use on the restorative treatment needs in young adults with attention deficit hyperactivity disorder. PARTICIPANTS AND METHODS: This retrospective study comprises a cohort of military recruits aged 18-25 who served for 12 to 48 months between 2005 and 2017. The medical records of 213 604 participants were assessed of which: 6875 participants with ADHD who received treatment with MP, 6729 participants with ADHD who had no prescriptions for MP, and 200 000 healthy participants. The outcome was restorative treatment needs, which served as an indicator of caries: having at least one prescription for restorative treatment during the study period. RESULTS: Frequency of prescription for restorative treatment among the treated, the untreated and the control groups was 24%, 22%, and 17%, respectively (p < .0001). On multivariate analysis, the dose-response association between MP use and the odds of having at least one restorative treatment was confirmed (OR = 1.006 for each additional 1 gr of MP; 95% CI [1.004:1.009]) CONCLUSIONS: Participants with ADHD who receive chronic treatment with MP have higher restorative treatment needs than participants with untreated ADHD and healthy participants. Our results show that chronic MP medication among young adults leads to an elevated need for restorative treatment and implies a significant impact on oral health (OH).

A social media analysis of kratom use to discontinue stimulants.

BACKGROUND: While FDA-approved treatments exist for opioid use disorder, none are available for stimulant use disorder. Kratom (Mitragyna speciosa), an unregulated plant-derived substance with known opioid- and stimulant-like effects, has been used to self-treat opioid use disorder; however, its use in relation to stimulant use disorder has not been described. OBJECTIVE: To understand whether and how individuals use kratom to self-treat stimulant use disorder. METHODS: Using a commercially available social listening platform, 3,820 publicly available social media posts published between January 1, 2020, and June 21, 2021, were reviewed for relevance to kratom and stimulant discontinuation. Manual qualitative thematic analysis was conducted on relevant data. RESULTS: Among the 398 relevant posts that discussed using kratom to discontinue stimulants, motivations and methods varied considerably. Posts predominantly identified benefits but also negative outcomes of kratom use. Some justified it as necessary despite consequences, while others reported a desire to quit. CONCLUSIONS: Although there is some awareness that kratom is used to self-treat opioid use disorder, its use to treat stimulant use disorder is more novel. In the absence of approved treatments, kratom was viewed as a natural and safe way to quit stimulants. Despite some reported success, this study shows self-treatment may pose significant risks, including kratom addiction and physical dependence. Healthcare practitioners, researchers, and public health professionals may benefit from understanding motivations for kratom use, associated benefits and risks, and the importance of discussing kratom use with patients/clients who have stimulant use disorder.

Methylamphetamine toxicity and its involvement in death: A retrospective observational study of deaths reported to the Victorian Coroner, Australia.

A retrospective observational study of Victorian deaths involving MA between 2010 and 2019 was conducted to determine the prevalence and contribution of methylamphetamine (MA) toxicity to death in the absence of other factors. Demographics, autopsy findings, toxicology, and the cause of death were reviewed. Coronial cases were categorized into five groups: deaths due to MA toxicity in the absence of other factors (Group A1); deaths due to MA toxicity in the setting of other potentially contributing factors (Group A2); deaths due to MA toxicity in the setting of significant natural disease (Group B); deaths primarily due to multiple-drug toxicity (Group C); and deaths primarily due to natural causes (Group D). There were 506 deaths involving MA categorized into Group A1 (n = 1, 0.6%), Group A2 (n = 8, 1.6%), Group B (n = 28, 5.5%), Group C (n = 229, 45%), and Group D (n = 240, 47%). Significant natural disease was prevalent among deaths involving MA and mainly concerned forms of cardiovascular disease (n = 277, 55%). The MA concentration in the one death included in Group A1 was 2.1 mg/L. The median MA concentrations of Group A2 (1.6 mg/L) and Group B (0.5 mg/L) were significantly higher than Group C (0.2 mg/L) and Group D (0.2 mg/L). Additionally, many other toxicologically significant drugs were detected and mostly comprised of central nervous system depressants. Deaths due to MA toxicity in the absence of other factors were rare despite the greater availability of crystal MA in the Australian community. The study highlights the interpretative challenges of MA blood concentrations and the continuing harms of this drug in Australia.

Drug overdose deaths in Brazil between 2000 and 2020: an analysis of sociodemographics and intentionality

Objectives: To examine drug overdose records in Brazil from 2000 to 2020, analyzing trends over time in overdoses and overall sociodemographic characteristics of the deceased. Methods: Using data from the Brazilian Mortality Information System (Sistema de Informações sobre Mortalidade), we identified records from 2000-2020 in which the underlying cause-of-death was one of the following codes: X40-X45 (accidental poisoning), X60-X65 (intentional poisoning), or Y10-Y15 (undetermined intentionality poisoning). The Brazilian dataset included 21,410 deaths. We used joinpoint regression analysis to assess changes in trends over time. Results: People who died of drug overdoses in Brazil between 2000 and 2020 had a mean age of 38.91 years; 38.45% were women, and 44.01% were identified as White. Of the overdose deaths, 44.70% were classified as intentional and 32.12% were classified as unintentional. Among the identified drugs, stimulants were the most common class. However, most records did not report which drug was responsible for death. Conclusion: Sociodemographic trends in overdose deaths in Brazil must guide country-specific policies. Nevertheless, data collection protocols must be improved, particularly regarding the drug used in overdoses.

Drug overdose deaths in Brazil between 2000 and 2020: an analysis of sociodemographics and intentionality.

OBJECTIVES: To examine drug overdose records in Brazil from 2000 to 2020, analyzing trends over time in overdoses and overall sociodemographic characteristics of the deceased. METHODS: Using data from the Brazilian Mortality Information System (Sistema de Informações sobre Mortalidade), we identified records from 2000-2020 in which the underlying cause-of-death was one of the following codes: X40-X45 (accidental poisoning), X60-X65 (intentional poisoning), or Y10-Y15 (undetermined intentionality poisoning). The Brazilian dataset included 21,410 deaths. We used joinpoint regression analysis to assess changes in trends over time. RESULTS: People who died of drug overdoses in Brazil between 2000 and 2020 had a mean age of 38.91 years; 38.45% were women, and 44.01% were identified as White. Of the overdose deaths, 44.70% were classified as intentional and 32.12% were classified as unintentional. Among the identified drugs, stimulants were the most common class. However, most records did not report which drug was responsible for death. CONCLUSION: Sociodemographic trends in overdose deaths in Brazil must guide country-specific policies. Nevertheless, data collection protocols must be improved, particularly regarding the drug used in overdoses.

Acute effects of energy drink consumption on cardiovascular parameters in healthy adults: a systematic review and meta-analysis of randomized clinical trials.

CONTEXT: Energy drinks (EDs) are beverages that contain ingredients that may pose a risk to consumers' cardiovascular health. But current evidence is conflicting and warrants further investigation. OBJECTIVE: A systematic review and meta-analysis was conducted on studies that examined the acute effects of ED consumption on systolic blood pressure (SBP), diastolic blood pressure (DBP), resting heart rate, cardiac output (CO), endothelial function, and QT/QTc interval in healthy adults. DATA SOURCES: The databases PubMed, EMBASE, Cochrane, LILACS, Web of Science, SportDiscus, and the gray literature were searched to identify randomized controlled trials (RCTs). DATA EXTRACTION: Two independent evaluators screened 2014 studies and extracted relevant data from those selected for the analysis. A risk of bias assessment was also performed with the RoB 2 tool and a strength of evidence assessment was performed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). DATA ANALYSIS: A total of 17 RCTs were included in the meta-analysis. With regard to risk of bias, 11 studies were rated as having "some concerns" and 6 as "high risk of bias." The consumption of EDs increased SBP, DBP, and CO in different time frames. More pronounced effects were seen on SBP at 60-80 minutes (4.71 mmHg; 95% CI: 2.97-6.45; GRADE: moderate), DBP at 120 minutes (4.51 mmHg; 95% CI: 2.60-6.42; GRADE: low), and CO at 30-40 minutes after consumption (0.43 L; 95% CI: 0.08-0.77; GRADE: very low). The effects of ED consumption on resting heart rate and QT/QTc interval were not significant (P ≤ 0.05). The assessment of endothelial function effects was not performed due to the absence of any RCTs meeting the inclusion criteria. CONCLUSIONS: Acute consumption of EDs increases SBP, DBP, and CO in healthy adults. However, no alterations were observed in other cardiovascular parameters. The results should be interpreted with caution due to the limited number of studies included in the analysis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022295335.

Overcoming defensive responding in the estimation of prevalence of non-medical use of prescription stimulants.

BACKGROUND: Prevalence of Non-Medical Use of Prescription Stimulants (NMUPS) is estimated to be high among young adults enrolled in college. However, precise estimation of the prevalence of NMUPS is challenging owing to biases affecting self-report of sensitive and potentially illegal behaviors. OBJECTIVE: This study aimed to estimate the prevalence and risk factors of NMUPS using the crosswise randomized response technique (CRRT) and compare findings to the traditionally-used direct self-report (DSR) method. METHODS: This study utilized a cross-sectional, randomized experimental design to survey adult undergraduate students at a major southeastern university in the United States. Eligible respondents were randomly assigned to a DSR group or a CRRT group. Those in the DSR group were presented a direct question about NMUPS, but those in the CRRT group were asked to indicate whether their response to the NMUPS question was the 'same' or 'different' compared to a random non-sensitive question. RESULTS: Prevalence of NMUPS was found to be 18.6% (95% CI:18.5%-18.7%) in the DSR group and 32.5% (95% CI:32.1%-32.9%; p = 0.003) in the CRRT group. Logistic regression analysis predicting NMUPS in the DSR group showed that it was significantly associated with positive expectancies (OR:3.50; 95% CI:2.44-5.02), negative expectancies (OR:0.49; 95% CI:0.35-0.68), perceived norms (OR:1.71; 95% CI:1.27-2.29), and religious beliefs (OR:0.69; 95% CI:0.52-0.92). CONCLUSIONS: The setting and mechanism of the survey is likely closely related to the validity of prevalence estimation of sensitive behaviors. This study found that prevalence of sensitive behaviors such as NMUPS is significantly higher when respondents are provided increased anonymity.

Attention-deficit hyperactivity disorder diagnoses and prescriptions in UK primary care, 2000-2018: population-based cohort study.

BACKGROUND: Rates of diagnosed attention-deficit hyperactivity disorder (ADHD) may be increasing in the UK. AIMS: Estimate incidence and prevalence of ADHD diagnoses and ADHD prescriptions in UK adults and children in primary care. METHOD: We conducted a cohort study using IQVIA Medical Research Data, a UK primary care database. Rates of ADHD diagnoses and ADHD prescriptions were calculated between 2000 and 2018 for individuals aged 3-99 years, analysed by age, gender, social deprivation status and calendar year. RESULTS: Of 7 655 931 individuals, 35 877 (0.5%) had ADHD diagnoses; 18 518 (0.2%) received ADHD medication prescriptions. Diagnoses and prescription rates were greater in men versus women, children versus adults, and deprivation status (nearly double in most deprived versus least deprived quintile). By 2018, the proportion of ADHD diagnoses was 255 per 10 000 (95% CI 247-263) in boys and 67.7 per 10 000 (95% CI 63.5-71.9) in girls; for adults, it was 74.3 per 10 000 (95% CI 72.3-76.2) in men and 20 per 10 000 (95%CI 19.0-21.0) in women. Corresponding figures for prescriptions were 156 per 10 000 (95% CI 150-163) in boys, 36.8 per 10 000 (95% CI 33.8-40.0) in girls, 13.3 per 10 000 (95% CI 12.5-14.1) in men and 4.5 per 10 000 (95% CI 4.1-5.0) in women. Except among 3- to 5-year-olds, the incidence and prevalence of ADHD diagnoses and prescriptions have increased from 2000 to 2018 in all age groups. The absolute increase was highest in children, but the relative increase was largest among adults (e.g. among men aged 18-29 years, approximately 20-fold and nearly 50-fold increases in diagnoses and prescriptions, respectively). CONCLUSIONS: The incidence and prevalence of both ADHD diagnoses and medication are highest among children. Proportionally, rates increased most among adults during 2000-2018. ADHD diagnoses and prescriptions are associated with socioeconomic deprivation.

Impact of a Publicly-Funded Pharmacare Program on Prescription Stimulant use Among Children and Youth: A Population-Based Observational Natural Experiment.

OBJECTIVE: Stimulants are first-line pharmacotherapy for individuals with attention-deficit hyperactivity disorder. However, disparities in drug coverage may contribute to inequitable treatment access. In January 2018, the government of Ontario, Canada, implemented a publicly-funded program (OHIP+) providing universal access to medications at no cost to children and youth between the ages of 0 and 24. In April 2019, the program was amended to cover only children and youth without private insurance. We studied whether these policy changes were associated with changes in prescription stimulant dispensing to Ontario children and youth. METHODS: We conducted a population-based observational natural experiment study of stimulant dispensing to children and youth in Ontario between January 2013 and March 2020. We used interventional autoregressive integrated moving average models to estimate the association between OHIP+ and its subsequent modification with stimulant dispensing trends. RESULTS: The implementation of OHIP+ was associated with a significant immediate increase in the monthly rate of stimulant dispensing of 53.6 individuals per 100,000 population (95% confidence interval [CI], 36.8 to 70.5 per 100,000) and a 14.2% (95% CI, 12.8% to 15.6%) relative percent increase in stimulant dispensing rates between December 2017 and March 2019 (1198.6 vs. 1368.7 per 100,000 population). The April 2019 OHIP+ program amendment was associated with an increase in monthly stimulant dispensing trends of 10.2 individuals per 100,000 population (95% CI, 5.0 to 15.5), with rates increasing 7.5% (95% CI, 6.2% to 8.7%) between March 2019 and March 2020 (1368.7 vs. 1470.8 per 100,000 population). These associations were most pronounced among males, children and youth living in the highest income neighbourhoods and individuals aged 20 to 24. CONCLUSION: A publicly-funded pharmacare program was associated with more children and youth being dispensed stimulants.

Exogenous Caffeine Ingestion Does Not Increase Plantarflexor Torque in Older or Younger Men.

Aging is associated with neurodegeneration and a loss of muscle function, especially in lower-limb muscles. While caffeine may augment muscle force generation through multiple effects on the central nervous system, no studies have yet compared the effects of caffeine on force-generating capacity between younger and older men, who might respond differently due to age-related changes in the structures on which caffeine acts. In a double-blind, controlled trial, 22 younger (25 ± 5 years) and 21 older (68 ± 6 years) men were tested for isometric plantarflexor torque on two separate days (2-7 days apart) before and 60 min after ingesting 3 mg/kg (∼2 cups of coffee) of caffeine or placebo. No effects of caffeine ingestion on peak torque or rate of torque development were detected in either older or younger men. Therefore, 3 mg/kg of caffeine may not acutely counteract age-related decreases in force capacity of the functionally important plantarflexor muscles.

Patterns of attention deficit hyperactivity disorder medicine use in the era of new non-stimulant medicines: A population-based study among Australian children and adults (2013-2020).

BACKGROUND AND AIMS: New therapeutic options such as lisdexamfetamine and guanfacine have recently become available for the treatment of attention deficit hyperactivity disorder. We described contemporary patterns of attention deficit hyperactivity disorder medicine use among children, adolescents and adults in Australia. METHODS: This population-based study used dispensing data for a 10% random sample of Australian residents between July 2012 and December 2020. We estimated the annual prevalence and incidence of attention deficit hyperactivity disorder medicines, second-line guanfacine use and examined concurrent medicine use of both stimulants and non-stimulants. We followed incident users for up to 5 years and analysed treatment persistence using a novel proportion of people covered method. Analyses were stratified by attention deficit hyperactivity disorder medicine, sex and age group; young children (0-5 years), children (6-12 years), adolescents (13-17 years), young adults (18-24 years) and adults (⩾25 years). RESULTS: We observed a twofold increase in the overall prevalence of attention deficit hyperactivity disorder medicine use between 2013 and 2020, from 4.9 to 9.7 per 1000 persons. Incident use also increased across all age groups and both sexes, with the most pronounced increases among adolescent females (from 1.4 to 5.3 per 1000 persons). Stimulant treatment persistence after 5 years was highest among those initiating treatment as young children (64%) and children (69%) and lowest among those initiating treatment in adolescence (19%). Concurrent use of stimulants and non-stimulants was more common among males and younger age groups. Most children (87%) initiating guanfacine had prior dispensings of attention deficit hyperactivity disorder medicines. CONCLUSION: We observed increasing attention deficit hyperactivity disorder medicine use in Australia, especially among young females. Nevertheless, treatment rates remain lower than the estimated prevalence of attention deficit hyperactivity disorder across all subpopulations. Poor long-term treatment persistence in adolescence may warrant improved clinical monitoring of attention deficit hyperactivity disorder in patients transitioning from paediatric to adult care. Reassuringly, use of newly approved guanfacine appeared to be in accordance with guidelines among children.

Prevalence trends and individual patterns of ADHD medication use in pregnancy in Norway and Sweden, 2010-2019.

PURPOSE: This study aimed to describe recent trends in ADHD medication use in pregnancy in Norway and Sweden, including prevalence, individual characteristics, and patterns of use. METHODS: We studied ADHD medication use (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine) by year and age in pregnancies from 2010 to 2019 identified from the medical birth registers (gestational age ≥ 22 weeks) linked to prescribed drug registers (Norway, N = 577,116; Sweden, N = 1,118,988). We compared characteristics of those who used any ADHD medication in pregnancy to no use in pregnancy. Discontinuation was defined as no use after first trimester. RESULTS: ADHD medication use increased from 2010 to 2019 by 3.0 users per 1000 pregnancies in Norway (from 2.5 to 5.5/1000) and by 6.3 per 1000 in Sweden (from 1.6 to 7.9/1000), mainly driven by methylphenidate and since 2015 by lisdexamfetamine. Medication use has increased among pregnant individuals of all age groups, with higher use among the youngest. Pregnant individuals who used ADHD medication were less likely to be married/cohabiting, more likely be nulliparous and to smoke. They had particularly high use of co-medication with antidepressants, anxiolytics/hypnotics, and opioids: 42% in Norway and 65% in Sweden used at least one additional class of psychotropic medication. Most individuals discontinued ADHD medication in pregnancy (85% Norway, 78% Sweden). CONCLUSION: ADHD medication use during pregnancy increased in Norway and Sweden in the last decade. However, discontinuation rates during pregnancy were high. Those who used ADHD medication had more risk factors for pregnancy complications including low parity, smoking, and other psychotropic drug use.

Trends in the Prevalence of Chronic Medication Use Among Children in Israel Between 2010 and 2019: Protocol for a Retrospective Cohort Study.

BACKGROUND: Prescription of psychostimulants has significantly increased in most countries worldwide for both preschool and school-aged children. Understanding the trends of chronic medication use among children in different age groups and from different sociodemographic backgrounds is essential. It is essential to distinguish between selected therapy areas to help decision-makers evaluate not only the relevant expected medication costs but also the specific services related to these areas. OBJECTIVE: This study will analyze differences in trends regarding medications considered psychobehavioral treatments and medications considered nonpsychobehavioral treatments and will identify risk factors and predictors for chronic medication use among children. METHODS: This is a retrospective study. Data will be extracted from the Clalit Health Services data warehouse. For each year between 2010 and 2019, there are approximately 1,500,000 children aged 0-18 years. All medication classes will be identified using the Anatomical Therapeutic Chemical code. A time-trend analysis will be performed to investigate if there is a significant difference between the trends of children's psychobehavioral and nonpsychobehavioral medication prescriptions. A logistic regression combined with machine learning models will be developed to identify variables that may increase the risk for specific chronic medication types and identify children likely to get such treatment. RESULTS: The project was funded in 2019. Data analysis is currently underway, and the results are expected to be submitted for publication in 2022. Understanding trends regarding medications considered psychobehavioral treatments and medications considered nonpsychobehavioral treatments will support the identification of risk factors and predictors for chronic medication use among children. CONCLUSIONS: Analyzing the response of the patient (and their parents or caregivers) population over time will hopefully help improve policies for prescriptions and follow-up of chronic treatments in children. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36756.

Stimulant use in suicides: A systematic review.

Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides attributable to substance use. This systematic review investigated any potential associations of stimulant use detected in post-mortem biological specimens and suicides. We conducted a systematic review and narrative synthesis (CRD42021237966). Medline, EMBASE, TOXLINE, and Scopus databases were searched for terms related to forensic toxicology, post-mortem toxicology, suicide and stimulants. The primary outcome was to estimate the prevalence of stimulant use in suicides. There were 26 studies whichcontributed to prevalence measures; in studies reporting at the individual compound level, suicides involved cocaine (0.1-23%), caffeine (3.2-22%), 3,4-methylenedioxymethamphetamine (0.1-17%), amphetamine (0.2-9.3%), methamphetamine (3.1-7%), and phentermine (0.9-1%). Overall, stimulant use in suicides was over-represented compared to estimates of stimulant use in the general population and has increased over time. Thirteen case reports used to contextualise suicides involving stimulants found no examples of cocaine or methamphetamine mono-intoxication of suicidal intent. This suggests mechanisms other than acute toxicity involved in stimulant-associated suicide. Future research by in-depth psychological autopsies of suicides involving stimulants, in combination with segmental hair analysis to determine the chronicity of stimulant exposure, may contribute to a better understanding of the burden of suicide attributable to stimulant use.