A critical review of the dextroamphetamine transdermal system for the treatment of ADHD in adults and pediatric patients.

INTRODUCTION: The dextroamphetamine transdermal system (d-ATS) is a stimulant patch recently approved by the United States (U.S.) Food and Drug Administration for the treatment of attention-deficit/hyperactivity disorder (ADHD). AREAS COVERED: The composition of the d-ATS, pharmacokinetics, and metabolism are presented along with data from dermal trials evaluating the tolerability of patch application at various skin sites. Efficacy and safety data from a laboratory classroom study in children and adolescents including effect sizes are assessed. Pharmacokinetic-pharmacodynamic modeling of variable wear times is also discussed. EXPERT OPINION: Although stimulants are recommended as first-line treatment for ADHD in the U.S. some patients may have difficulty swallowing intact tablets and capsules, or dislike the taste or texture of chewable, oral disintegrating, or liquid formulations. The d-ATS fills an unmet need for those with ADHD who are unable or prefer not to take medication orally. Varying wear time of the d-ATS also gives flexibility in length of stimulant effect which may be useful for patients with changing schedules. However, dermal discomfort must be considered in addition to the usual amphetamine side effects when prescribing the d-ATS. Patient and provider experience will determine how frequent the use of d-ATS becomes.

[Wakefulness-promoting agents for severe fatigue: to use or not to use?] / Medicatie tegen ernstige aanhoudende vermoeidheid.

About 20% of adults experience excessive daytime sleepiness or severe fatigue. Causes include somatic conditions, psychiatric disorders, and medication or drug use. Treatment depends on the underlying cause. If sleepiness persists despite optimal treatment of the underlying condition, exclusion of other causes, and behavioral interventions, wakefulness-promoting agents may be considered. However, no established pharmacological strategy exists for symptomatic treatment. Modafinil and stimulants like methylphenidate may offer some benefit based on experiences with narcolepsy or idiopathic hypersomnia. Studies in specific patient groups (e.g., multiple sclerosis, Parkinson's disease, traumatic brain injury, cancer-related fatigue) show variable results. The use of wakefulness-promoting agents is discouraged for addressing unexplained fatigue, as seen in the context of chronic fatigue syndrome.

Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry.

BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

Psychosis with use of amphetamine drugs, methylphenidate and atomoxetine in adolescent and adults.

BACKGROUND: Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants. OBJECTIVE: To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD. METHODS: Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR). FINDINGS: Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine. CONCLUSION: Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use. CLINICAL IMPLICATIONS: The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.

Fetal alcohol spectrum disorder and attention deficit hyperactivity disorder stimulant trial in children: an N-of-1 pilot trial to compare stimulant to placebo (FASST): protocol.

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by alcohol exposure during pregnancy. FASD is associated with neurodevelopmental deviations, and 50%-94% of children with FASD meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition diagnostic criteria for attention deficit hyperactivity disorder (ADHD). There is a paucity of evidence around medication efficacy for ADHD symptoms in children with FASD. This series of N-of-1 trials aims to provide pilot data on the feasibility of conducting N-of-1 trials in children with FASD and ADHD. METHODS AND ANALYSIS: A pilot N-of-1 randomised trial design with 20 cycles of stimulant and placebo (four cycles of 2-week duration) for each child will be conducted (n=20) in Melbourne, Australia.Feasibility and tolerability will be assessed using recruitment and retention rates, protocol adherence, adverse events and parent ratings of side effects. Each child's treatment effect will be determined by analysing teacher ADHD ratings across stimulant and placebo conditions (Wilcoxon rank). N-of-1 data will be aggregated to provide an estimate of the cohort treatment effect as well as individual-level treatment effects. We will assess the sample size and number of cycles required for a future trial. Potential mediating factors will be explored to identify variables that might be associated with treatment response variability. ETHICS AND DISSEMINATION: The study was approved by the Hospital and Health Service Human Research Ethics Committee (HREC/74678/MonH-2021-269029), Monash (protocol V6, 25 June 2023).Individual outcome data will be summarised and provided to participating carers and practitioners to enhance care. Group-level findings will be presented at a local workshop to engage stakeholders. Findings will be presented at national and international conferences and published in peer-reviewed journals. All results will be reported so that they can be used to inform prior information for future trials. TRIAL REGISTRATION NUMBER: NCT04968522.

Substance use patterns, sociodemographics, and health profiles of harm reduction service recipients in Burlington, Vermont.

BACKGROUND: Understanding current substance use practices is critical to reduce and prevent overdose deaths among individuals at increased risk including persons who use and inject drugs. Because individuals participating in harm reduction and syringe service programs are actively using drugs and vary in treatment participation, information on their current drug use and preferred drugs provides a unique window into the drug use ecology of communities that can inform future intervention services and treatment provision. METHODS: Between March and June 2023, 150 participants in a harm reduction program in Burlington, Vermont completed a survey examining sociodemographics; treatment and medication for opioid use disorder (MOUD) status; substance use; injection information; overdose information; and mental health, medical, and health information. Descriptive analyses assessed overall findings. Comparisons between primary drug subgroups (stimulants, opioids, stimulants-opioids) of past-three-month drug use and treatment participation were analyzed using chi-square and Fisher's exact test. RESULTS: Most participants reported being unhoused or unstable housing (80.7%) and unemployed (64.0%) or on disability (21.3%). The drug with the greatest proportion of participants reporting past three-month use was crack cocaine (83.3%). Fentanyl use was reported by 69.3% of participants and xylazine by 38.0% of participants. High rates of stimulant use were reported across all participants independent of whether stimulants were a participant's primary drug. Fentanyl, heroin, and xylazine use was less common in the stimulants subgroup compared to opioid-containing subgroups (p < .001). Current- and past-year MOUD treatment was reported by 58.0% and 77.3% of participants. Emergency rooms were the most common past-year medical treatment location (48.7%; M = 2.72 visits). CONCLUSIONS: Findings indicate high rates of polysubstance use and the underrecognized effects of stimulant use among people who use drugs-including its notable and increasing role in drug-overdose deaths. Crack cocaine was the most used stimulant, a geographical difference from much of the US where methamphetamine is most common. With the increasing prevalence of fentanyl-adulterated stimulants and differences in opioid use observed between subgroups, these findings highlight the importance and necessity of harm reduction interventions (e.g., drug checking services, fentanyl test strips) and effective treatment for individuals using stimulants alongside MOUD treatment.

Viloxazine extended-release capsules as an emerging treatment for attention-deficit/hyperactivity disorder in children and adolescents.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention and/or hyperactivity and impulsivity. Viloxazine extended-release (ER) capsules (Qelbree®) is a US Food and Drug Administration-approved nonstimulant treatment option for children, adolescents, and adults with ADHD. AREAS COVERED: This review manuscript summarizes the neurobiology of ADHD and currently available treatment options before discussing viloxazine pharmacology, efficacy, safety, and tolerability data from phase II and III trials in children and adolescents (6-17 years old). Viloxazine clinical efficacy has also been further demonstrated by post hoc analyses of pediatric clinical trial results. EXPERT OPINION: Current stimulant and nonstimulant treatments for ADHD may be suboptimal given low response rates and that tolerability issues are frequently experienced. Preclinical and clinical evidence has implicated both the role of catecholamine and serotonin signaling in the pathophysiology of ADHD and the pharmacologic effect of viloxazine on these critical neurotransmitter systems. With a relatively rapid onset of action, sustained symptom improvement, and clinical benefit in ADHD-associated impairments (functional and social), viloxazine ER represents a novel and emerging ADHD treatment option.

Treatments for ADHD in Children and Adolescents: A Systematic Review.

CONTEXT: Effective treatment of attention-deficit/hyperactivity disorder (ADHD) is essential to improving youth outcomes. OBJECTIVES: This systematic review provides an overview of the available treatment options. DATA SOURCES: We identified controlled treatment evaluations in 12 databases published from 1980 to June 2023; treatments were not restricted by intervention content. STUDY SELECTION: Studies in children and adolescents with clinically diagnosed ADHD, reporting patient health and psychosocial outcomes, were eligible. Publications were screened by trained reviewers, supported by machine learning. DATA EXTRACTION: Data were abstracted and critically appraised by 1 reviewer and checked by a methodologist. Data were pooled using random-effects models. Strength of evidence and applicability assessments followed Evidence-based Practice Center standards. RESULTS: In total, 312 studies reported in 540 publications were included. We grouped evidence for medication, psychosocial interventions, parent support, nutrition and supplements, neurofeedback, neurostimulation, physical exercise, complementary medicine, school interventions, and provider approaches. Several treatments improved ADHD symptoms. Medications had the strongest evidence base for improving outcomes, including disruptive behaviors and broadband measures, but were associated with adverse events. LIMITATIONS: We found limited evidence of studies comparing alternative treatments directly and indirect analyses identified few systematic differences across stimulants and nonstimulants. Identified combination of medication with youth-directed psychosocial interventions did not systematically produce better results than monotherapy, though few combinations have been evaluated. CONCLUSIONS: A growing number of treatments are available that improve ADHD symptoms and other outcomes, in particular for school-aged youth. Medication therapies remain important treatment options but are associated with adverse events.

Attention deficit and hyperactivity disorder and use of psychostimulants in Aotearoa, New Zealand: exploring the treatment gap.

Introduction Attention deficit and hyperactivity disorder (ADHD) is a common neurodevelopmental disorder affecting about 7% of those aged up to 12 years, 5% of teenagers and 3% of adults. It is associated with poor academic performance, substance abuse, criminality, poor social functioning and other negative outcomes. Psychotherapeutic treatment is moderately successful, whereas pharmacotherapy with stimulant medication is more efficacious and is recommended in many international guidelines. Anecdotal evidence suggests underuse of these medications in Aotearoa, New Zealand. Aim To estimate how many patients with ADHD are prescribed psychostimulants in Aotearoa, New Zealand. Methods National prescribing data for dexamphetamine and methylphenidate in 2022 were obtained and matched against estimated prevalence of ADHD by age. Results There is a significant treatment gap for which inability to access first-line medication is likely to be the predominant explanation. Discussion The data suggest failure of our health system to provide reasonable health care for a significant number of people with ADHD, and results in inequity in outcomes. New approaches are needed that will increase access to first-line medication, yet maintain appropriateness of diagnosis and limit risk of medication diversion.

Memory loss induced by lisdexamfetamine in the rat: A behavioral, electrophysiological, and histopathological Study.

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.

ADHD Pharmacotherapy and Mortality in Individuals With ADHD.

Importance: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. Objective: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. Design, Setting, and Participants: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first. Exposures: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. Main Outcomes and Measures: We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings). Results: Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05). Conclusions and Relevance: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

Modeling methamphetamine use disorder in mammals: Sex differences in behavioral, biochemical, and transcriptional consequences.

Methamphetamine (METH) is the most commonly misused amphetamine-type stimulant throughout the globe. METH is very rewarding, and its misuse can lead to a diagnosis of METH use disorder (MUD). Although METH use is observed in both sexes, there are, however, reported differences in the clinical manifestations of METH use and its consequences. These observations indicate the need for more research on the long-term sex-dependent consequences of METH taking in both preclinical and clinical settings. In effect, sex is a biological variable that can impact conclusions drawn from various basic and clinical studies. Thus, the present chapter provides a succinct review of the current state of the research on METH and its sex-associated consequences. In addition to behavioral and cognitive aspects of METH use, we discuss METH-induced changes in neurotransmitter systems and structures in the brain. Thus, the book chapter serves to highlight the significance of sex as a critical element that needs to be considered during discussions of novel therapeutic approaches to MUD.

Modafinil, an atypical CNS stimulant?

Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an "atypical" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders.

The pharmacology and neurotoxicology of synthetic cathinones.

The synthetic cathinones are man-made compounds derived from the naturally occurring drug cathinone, which is found in the khat plant. The drugs in this pharmacological class that will be the focus of this chapter include mephedrone, MDPV, methcathinone and methylone. These drugs are colloquially known as "bath salts". This misnomer suggests that these drugs are used for health improvement or that they have legitimate medical uses. The synthetic cathinones are dangerous drugs with powerful pharmacological effects that include high abuse potential, hyperthermia and hyperlocomotion. These drugs also share many of the pharmacological effects of the amphetamine class of drugs including methamphetamine, amphetamine and MDMA and therefore have high potential to cause damage to the central nervous system. The synthetic cathinones are frequently taken in combination with other psychoactive drugs such as alcohol, marijuana and the amphetamine-like stimulants, creating a situation where heightened pharmacological and neurotoxicological effects are likely to occur. Despite the structural features shared by the synthetic cathinones and amphetamine-like stimulants, including their actions at monoamine transporters and receptors, the effects of the synthetic cathinones do not always match those of the amphetamines. In particular, the synthetic cathinones are far less neurotoxic than their amphetamine counterparts, they produce a weaker hyperthermia, and they cause less glial activation. This chapter will briefly review the pharmacology and neurotoxicology of selected synthetic cathinones with the aim of delineating key areas of agreement and disagreement in the literature particularly as it relates to neurotoxicological outcomes.

Structural and functional perspectives on interactions between synthetic cathinones and monoamine transporters.

Synthetic cathinone derivatives comprise a family of psychoactive compounds structurally related to amphetamine. Over the last decade, clandestine chemists have synthesized a consistent stream of innovative cathinone derivatives to outpace governmental regulatory restrictions. Many of these unregulated substances are produced and distributed as designer drugs. Two of the principal chemical scaffolds exploited to expand the synthetic cathinone family are methcathinone and α-pyrrolidinopentiophenone (or α-pyrrolidinovalerophenone, α-PVP). These compounds' main physiological targets are monoamine transporters, where they promote addiction by potentiating dopaminergic neurotransmission. This chapter describes techniques used to study the pharmacodynamic properties of cathinones at monoamine transporters in vitro. Biochemical techniques described include uptake inhibition and release assays in rat brain synaptosomes and in mammalian expression systems. Electrophysiological techniques include current measurements using the voltage clamp technique. We describe a Ca2+ mobilization assay wherein voltage-gated Ca2+ channels function as reporters to study the action of synthetic cathinones at monoamine transporters. We discuss results from systematic structure-activity relationship studies on simple and complex cathinones at monoamine transporters with an emphasis on identifying structural moieties that modulate potency and selectivity at these transporters. Moreover, different profiles of selectivity at monoamine transporters directly predict compounds associated with behavioral and subjective effects within animals and humans. In conclusion, clarification of the structural aspects of compounds which modulate potency and selectivity at monoamine transporters is critical to identify and predict potential addictive drugs. This knowledge may allow prompt allocation of resources toward drugs that represent the greatest threats after drugs are identified by forensic laboratories.

Stimulant prodrugs: A pharmacological and clinical assessment of their role in treating ADHD and binge-eating disorder.

In this review, we critically evaluate the contribution of prodrugs to treating two related psychiatric disorders, attention-deficit hyperactivity disorder (ADHD) and binge-eating disorder (BED). ADHD is characterized by inattentiveness, distractibility, impulsiveness, and hyperactivity. BED is also an impulse-control disorder which leads to frequent, compulsive episodes of excessive eating (binges). Lisdexamfetamine (LDX; prodrug of d-amphetamine) is approved to treat both ADHD and BED. Serdexmethylphenidate (SDX; prodrug of d-threo-methylphenidate) is not clinically approved as monotherapy but, in a fixed-dose combination with immediate release d-threo-methylphenidate (Azstarys™), SDX is approved for managing ADHD in children/adolescents. The pharmacological actions of a stimulant mediate both its efficacy and side-effects. Therefore, daily management of ADHD or BED to maintain optimum efficacy and tolerability places highly restrictive requirements on the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of stimulant medications, especially prodrugs. Prodrugs must have good bioavailability and rapid metabolism to provide therapeutic efficacy soon after morning dosing combined with providing stimulant coverage throughout the day/evening. A wide selection of dosages and linear PK for the prodrug and its active metabolite are essential requirements for treatment of these conditions. The proposed neurobiological causes of ADHD and BED are described. The chemical, pharmacological and PK/PD properties responsible for the therapeutic actions of the prodrugs, LDX and SDX, are compared and contrasted. Finally, we critically assess their contribution as ADHD and BED medications, including advantages over their respective active metabolites, d-amphetamine and d-threo-methylphenidate, and also their potential for misuse and abuse.

Changes in real-world dispensing of ADHD stimulants in youth from 2019 to 2021 in California.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common pediatric neurobehavioral disorders in the U.S. Stimulants, classified as controlled substances, are commonly used for ADHD management. We conducted an analysis of real-world stimulants dispensing data to evaluate the pandemic's impact on young patients (≤ 26 years) in California. Methods: Annual prevalence of patients on stimulants per capita across various California counties from 2019 and 2021 were analyzed and further compared across different years, sexes, and age groups. New patients initiating simulants therapy were also examined. A case study was conducted to determine the impact of socioeconomic status on patient prevalence within different quintiles in Los Angeles County using patient zip codes. Logistic regression analysis using R Project was employed to determine demographic factors associated with concurrent use of stimulants with other controlled substances. Results: There was a notable reduction in prevalence of patients ≤26 years old on stimulants during and after the pandemic per 100,000 people (777 in 2019; 743 in 2020; 751 in 2021). These decreases were more evident among the elementary and adolescent age groups. The most prevalent age group on stimulants were adolescents (12-17 years) irrespective of the pandemic. A significant rise in the number of female patients using stimulants was observed, increasing from 107,957 (35.2%) in 2019 to 121,241 (41.1%) in 2021. New patients initiating stimulants rose from 102,754 in 2020 to 106,660 in 2021, with 33.2% being young adults. In Los Angeles County, there was an increasing trend in patient prevalence from Q1 to Q5 income quintiles among patients ≥6 years. Consistently each year, the highest average income quintile exhibited the highest per capita prevalence. Age was associated with higher risk of concurrent use of benzodiazepines (OR, 1.198 [95% CI, 1.195-1.201], p < 0.0001) and opioids (OR, 1.132 [95% CI, 1.130-1.134], p < 0.0001) with stimulants. Discussion: Our study provides real-world information on dispensing of ADHD stimulants in California youth from 2019 to 2021. The results underscore the importance of optimizing evidence-based ADHD management in pediatric patients and young adults to mitigate disparities in the use of stimulants.

Suicide, Stimulants, and Selective Serotonin Reuptake Inhibitors: A Retrospective Chart Review.

Background: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) may increase the risk of suicide among children and youth, although the association between suicide risk and the combination of SSRIs with other medication such as stimulants in this population remains unclear. This study explored whether the combination of SSRIs with stimulants influenced suicide risk. Methods: A retrospective cohort study was conducted at a single children's hospital campus-based ambulatory psychiatric clinic between September 1, 2017, and September 30, 2020. Subjects were 6-21 years of age and prescribed either stimulants or stimulants and SSRIs only. The primary outcome was suicidal thoughts and behaviors (STB), defined by documented suicidal thoughts, plans, or behaviors. Firth logistic regression evaluated associations between medication class and STB. Results: Among 349 patients, the prevalence of STB was 5.7% (n = 20). In unadjusted model, patients prescribed SSRIs and stimulants had a 2.9-fold increase of STB compared to patients prescribed stimulants only, along with increasing age, male sex, and the diagnoses of anxiety and/or depression. In the final model adjusted for each of these factors, the observed association of medication regiment with STB was attenuated (odds ratio [OR]: 1.3, confidence interval [CI]: 0.3-4.9, p = 0.7). The magnitude of the adjusted association between depressive diagnosis and STB was notable (OR: 3.6, CI: 1.0-12.6, p = 0.049). Conclusions: Among patients followed in a children's hospital-based ambulatory psychiatric clinic, a combination medication regimen of SSRIs and stimulants after adjusting for genetic sex, age, anxiety diagnosis, and depression diagnosis, the observed association between STB and combination stimulant and SSRI treatment was attenuated. This finding suggests that other factors, including depression, may have contributed to the association between SSRI treatment and STB. Larger, prospective studies of the relationship between combination pharmacotherapy and suicide risk are warranted to guide clinical/pharmacological decision making and to better clarify these relationships.