Stimulant Medication For Attention Deficit Hyperactivity Disorder Research Articles

Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life

We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to understand whether this effect differs between stimulants and non-stimulants. From the dataset of a published network meta-analysis (Cortese etal., 20181), updated on 27th February 2023 (https://med-adhd.org/), we identified randomized controlled trials (RCTs) of ADHD medications for individuals aged 6 years or more with a diagnosis of ADHD based on the DSM (from third to fifth editions) or the International Classification of Diseases (ICD; ninth or tenth revision), reporting data on QoL (measured with a validated scale). The risk of bias for each RCTs was assessed using the Cochrane Risk of Bias tool 2. Multi-level meta-analytic models were conducted with R 4.3.1. We included 17 RCTs (5,388 participants in total; 56% randomized to active medication) in the meta-analyses. We found that amphetamines (Hedges g= 0.51, 95% CI= 0.08, 0.94), methylphenidate (0.38; 0.23, 0.54), and atomoxetine (0.30; 0.19, 0.40) were significantly more efficacious than placebo in improving QoL in people with ADHD, with moderate effect size. For atomoxetine, these effects were not moderated by the length of intervention, and did not differ between children/adolescents and adults. In addition to being efficacious in reducing ADHD core symptom severity, both stimulant and non-stimulant medications are efficacious in improving QoL in people with ADHD, albeit with lower effect sizes. Future research should explore whether, and to what degree, combining pharmacological and non-pharmacological interventions is likely to further improve QoL in people with ADHD. Effects of pharmacological treatment for ADHD on quality of life: a systematic review and meta-analysis; https://osf.io/;qvgps.

The longitudinal influence of ADHD status and stimulant medication on body mass index and blood pressure among youth with obesity.

Youth with attention-deficit hyperactivity disorder (ADHD) are more vulnerable to developing obesity. Stimulant medication use, an evidence-based treatment for ADHD, is associated with lower body mass index (BMI) and higher blood pressure among non-overweight youth. The purpose of this study was to examine the longitudinal influence of ADHD and stimulant medication use on BMI and blood pressure among a sample of 456 youth with overweight and obesity treated in a paediatric weight management clinic. Mixed linear modelling examined the main and interactive effects of time by ADHD status and stimulant medication use on BMI and blood pressure. Youth without ADHD experienced a significantly faster decrease in BMI compared to youth with ADHD (p < 0.001). Youth with ADHD who were taking stimulant medication had a significantly faster decrease in BMI compared to youth with ADHD who were not taking stimulant medication (p = 0.009). There was no significant effect of ADHD status or stimulant medication use on diastolic or systolic blood pressure trajectories over time (ps >0.05). Results from this study suggest that youth with ADHD who are not taking stimulant medication may not benefit from clinical weight management to the same extent as either youth without ADHD or youth with ADHD who are taking a stimulant medication.

NIDA study finds link between ADHD stimulant medication and stimulant misuse

Researchers at the University of Michigan have found a strong association between prevalence of prescription stimulant therapy for attention‐deficit/hyperactivity disorder (ADHD) and rates of prescription stimulant misuse according to a study published last week in JAMA Network Open. The study, funded by the National Institute on Drug Abuse (NIDA) and part of the Monitoring the Future database, highlights the need for schools to make sure students don't share their medication, according to NIDA.

Stimulant Use for ADHD in a Cardiac Transplant Recipient: A Case Report

AbstractIntroductionMethylphenidate is a central nervous system stimulant used as first-line treatment for attention-deficit/hyperactivity disorder (ADHD). CNS stimulant use is associated with increased risk of cardiovascular events such as increased resting heart rate and blood pressure, sudden cardiac death, arrhythmia, and stroke. Its safety profile in recipients of cardiovascular transplants is unknown, and more research is warranted to determine the risk of adverse cardiac events due to stimulant medication in this population.MethodsClinical case report, n=1Results/Clinical CaseA 19-year-old female with a history of restrictive cardiomyopathy, cardiac arrest, and orthotopic cardiac transplant has been treated with methylphenidate for ADHD for approximately 2 years without incident. The patient was diagnosed with ADHD between the ages of 8 and 10 and historically was treated with stimulant medication. At age 13, she experienced a cardiac arrest after a volleyball game with 4–6 minutes of pulselessness. She was successfully resuscitated and underwent defibrillator placement. It was concluded that the patient had restrictive cardiomyopathy undetected at birth, leading to the need for orthotopic cardiac transplantation at age 16. After her cardiac arrest, the patient’s memory and cognition worsened, and approximately 1 year after her transplant, she was prescribed amantadine. The patient remained untreated for her ADHD until approximately 1.5 years after her cardiac transplant, at which time she underwent neuropsychological testing that showed findings consistent with attention deficit disorder, and was restarted on stimulant medication. Her transplant cardiologist and psychiatrist have collaborated in her ongoing treatment with methylphenidate 40 mg daily and monitoring symptom response and cardiac stability. Because the patient had previously been stable on stimulant medication for many years, it is reasonable to conclude that stimulant medication did not lead to her cardiac arrest. The patient reports that methylphenidate has been helpful in improving her functioning as a college student, through reduction of her ADHD symptoms. The patient’s blood pressure and heart rate remain within an acceptable range and she has not experienced any adverse cardiac events to date while taking methylphenidate.ConclusionThis case sheds light on the potential to treat cardiac transplant recipients with stimulant medication for ADHD. Although a careful evaluation of risk factors must be undertaken in cooperation with cardiology and other specialists, a role exists for the safe use of stimulant medications in the cardiac transplant population.FundingNo Funding

ADHD stimulant medication misuse and considerations for current prescribing practice: a literature review.

Stimulant medications have been prescribed to effectively treat childhood Attention Deficit Hyperactivity Disorder (ADHD) since the 1960's, with improved outcomes observed in the three core symptom domains. Over the course of these decades researchers and clinicians have debated the issue of negative outcomes with regard to later development of substance use disorders (SUD) for these children. To chronicle the development of medical and scientific opinion on the subject of SUD outcomes in ADHD and to appraise most recently published research in this sphere. A systematic search of the literature was conducted over 4 databases. Removal of duplicates, application of exclusion criteria and inclusion of publications identified through manual and citation-based search yielded 9 papers. Prescriptions for stimulant medications are increasing worldwide and in tandem the prevalence of stimulant misuse. Much research focuses on non-medical stimulant misuse as a study aid; however, they are also used as recreational drugs with action on dopaminergic neurotransmitter pathways implicated in addiction disorders. Considering the risks and benefits of stimulant prescribing on later SUD development research in recent decades has produced inconsistent results. Current research supports the hypothesis of improved SUD outcomes for young people treated early and intensely, with poorer outcomes for those with less robust treatment histories. Consideration of the impact that variable treatment trajectories may have on the risk of later SUD development is recommended, with further research potentially leading to the development of different management pathways based on an individual's multivariate treatment profile.

Association of Alopecia Areata With Attention-Deficit/Hyperactivity Disorder Stimulant Medication: A Case-Control Study.

Background: Both psychiatric disorders and diverse medications used to treat them have been associated with alopecia. The objective of our study was to investigate the existence of an association between attention-deficit/hyperactivity disorder (ADHD) stimulant medication (ASM) and various types of alopecia.Methods: We conducted a retrospective case-control medical record review of patients between the ages of 6 and 18 years seen in dermatology clinics during a 10-year period. Cases included patients diagnosed with alopecia areata (AA), alopecia totalis (AT), or alopecia universalis (AU). We matched 3 controls on age and sex to each case. We reviewed patients’ medical records for the following medications: lisdexamfetamine, amphetamine/dextroamphetamine, dexmethylphenidate, and methylphenidate. We examined the association between medications used to treat ADHD and diagnoses of AA, AT, and/or AU by calculating a series of odds ratios and 95% CIs.Results: We identified 124 cases (110 with AA, 11 with AT, and 3 with AU) and 372 controls. We found a strong association between AU and ASM use (P<0.0071). No relationship between ASM use and other types of hair loss was found.Conclusion: Although the sample size of cases with AU was small, we found a significant association between AU and ASM. While further study is needed, practitioners may consider close monitoring of patients with AA who use ASM for the development of worsening disease and discontinue the medication if the patient experiences an increase in hair loss that appears to be progressing to AU.

Real-World Changes in Adolescents' ADHD Symptoms within the Day and across School and Non-school Days.

Research on attention-deficit/hyperactivity disorder (ADHD) points to the possibility that contextual factors (e.g., time of day, school vs. home) may be related to symptoms and impairment. This prior research has relied on laboratory-based or retrospective, global approaches which has limited ecological validity. The present study substantively contributes to the extant literature by examining adolescents' ADHD symptoms in the real world across the day on both school and non-school days to test whether symptoms worsened throughout the day and were higher on school days relative to non-school days. As part of a larger study, 83 adolescents taking stimulant medication for ADHD (Mage = 14.7, 66% identified as boys/men, 78% White) completed a 17-day ecological momentary assessment protocol that included wake-up and bedtime reports and two reports in the afternoon and evening. These assessments asked about ADHD symptoms and stimulant medication usage since the last report. Hypotheses were tested using multilevel modeling. Accounting for demographic covariates and medication usage, ADHD symptoms worsened quadratically, peaking by the afternoon report and subsequently declining, across school days but not non-school days. Mean-level ADHD symptoms were also worse on school days relative to non-school days. Results did not differ across gender. In conclusion, our study is the first to examine important environmental factors (school, time of day) in real time in relation to level of naturalistically occurring ADHD symptoms. Our findings highlight the importance of advancing treatments to support adolescents with ADHD on school days and in the afternoon.

Interventions can improve weight but not height: growth study of ADHD stimulant medication

Drug holidays, more calories, and increased monitoring can help children who take stimulant medications for attention‐deficit/hyperactivity disorder (ADHD) gain weight, but they won't help the children grow taller. This is the lesson from a study published in the October 2019 issue of the Journal of the American Academy of Child &amp; Adolescent Psychiatry. The study looked at the effects of central nervous system (CNS) stimulants on the growth of children with ADHD, which included an assessment of weight interventions on growth.

EEG power spectral slope differs by ADHD status and stimulant medication exposure in early childhood.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by hyperactivity/impulsivity and inattentiveness. Efforts toward the development of a biologically based diagnostic test have identified differences in the EEG power spectrum; most consistently reported is an increased ratio of theta to beta power during resting state in those with the disorder, compared with controls. Current approaches calculate theta/beta ratio using fixed frequency bands, but the observed differences may be confounded by other relevant features of the power spectrum, including shifts in peak oscillation frequency and altered slope or offset of the aperiodic 1/f-like component of the power spectrum. In the present study, we quantify the spectral slope and offset, peak alpha frequency, and band-limited and band-ratio oscillatory power in the resting-state EEG of 3- to 7-yr-old children with and without ADHD. We found that medication-naive children with ADHD had higher alpha power, greater offsets, and steeper slopes compared with typically developing children. Children with ADHD who were treated with stimulants had comparable slopes and offsets to the typically developing group despite a 24-h medication-washout period. We further show that spectral slope correlates with traditional measures of theta/beta ratio, suggesting the utility of slope as a neural marker over and above traditional approaches. Taken with past research demonstrating that spectral slope is associated with executive functioning and excitatory/inhibitory balance, these results suggest that altered slope of the power spectrum may reflect pathology in ADHD.NEW & NOTEWORTHY This article highlights the clinical utility of comprehensively quantifying features of the EEG power spectrum. Using this approach, we identify, for the first time, differences in the aperiodic components of the EEG power spectrum in children with attention-deficit/hyperactivity disorder (ADHD) and provide evidence that spectral slope is a robust indictor of an increase in low- relative to high-frequency power in ADHD.

Association of Attention-Deficit/Hyperactivity Disorder With Teenage Birth Among Women and Girls in Sweden

Attention-deficit/hyperactivity disorder (ADHD) is associated with a plethora of adverse health outcomes throughout life. While Swedish specialized youth clinics have carefully and successfully targeted risk of unplanned pregnancies in adolescents, important risk groups, such as women and girls with ADHD, might not be identified or appropriately assisted by these interventions. To determine whether women and girls with ADHD are associated with increased risk of teenage birth compared with their unaffected peers and to examine the association of ADHD with risk factors for adverse obstetric and perinatal outcomes, such as smoking, underweight or overweight, and substance use disorder. This nationwide cohort study included data from 6 national longitudinal population-based registries in Sweden. All nulliparous women and girls who gave birth in Sweden between January 1, 2007, and December 31, 2014, were included. Data analyses were conducted from October 7, 2018, to February 8, 2019. Women and girls treated with stimulant or nonstimulant medication for ADHD (Anatomic Therapeutic Chemical classification code N06BA) in the Swedish Prescribed Drug Register between July 1, 2005, and December 31, 2014. Maternal age at birth. Secondary outcome measures were body mass index, smoking habits, and psychiatric comorbidities. Among 384 103 nulliparous women and girls aged 12 to 50 years who gave birth between 2007 and 2014 included in the study, 6410 (1.7%) (mean [SD] age, 25.0 [5.5] years) were identified as having ADHD. The remaining 377 693 women and girls without ADHD (mean [SD] age, 28.5 [5.1] years) served as the control group. Teenage deliveries were more common among women and girls with ADHD than among women and girls without ADHD (15.3% vs 2.8%; odds ratio [OR], 6.23 [95% CI, 5.80-6.68]). Compared with women and girls without ADHD, those with ADHD were more likely to present with risk factors for adverse obstetric and perinatal outcomes, including smoking during the third trimester (OR, 6.88 [95% CI, 6.45-7.34]), body mass index less than 18.50 (OR, 1.29 [95% CI, 1.12-1.49]), body mass index more than 40.00 (OR, 2.01 [95% CI, 1.60-2.52]), and alcohol and substance use disorder (OR, 20.25 [95% CI, 18.74-21.88]). This study found that women and girls with ADHD were associated with an increased risk of giving birth as teenagers compared with their unaffected peers. The results suggest that standard of care for women and girls with ADHD should include active efforts to prevent teenage pregnancies.

What is the effect of ADHD stimulant medication on heart rate and blood pressure in a community sample of children?

This study examines the effect of ADHD (attention deficit hyperactivity disorder) diagnosis and stimulant medication for ADHD treatment on child heart rate (HR) and blood pressure (BP) in a community sample compared to children without ADHD. Data came from the HBEAT Study. From 49 schools, 2013 participants from southern Ontario in grades 5-8 were included. Linear regression analyses examined the effects of ADHD medications on systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate adjusting for age, sex and body mass index (BMI). Compared to non-ADHD children and adjusting for age, sex and BMI, children with ADHD on stimulant medication had a 12.3-bpm higher HR, and 3.0-mmHg higher SBP and DBP (all statistically significant). Children with ADHD on no stimulant medication had no differences in HR and BP compared to those children without a diagnosis of ADHD. Stimulant medications used to treat ADHD are associated with elevated HR and higher BP. While it is unknown whether children on ADHD medications may be at risk for longer-term cardiovascular issues, this study supports the need to examine the long-term consequences of ADHD medication.

Parents Divert Their Children's ADHD Stimulant Medications

It is well known that some adolescents with attention-deficit/hyperactivity disorder (ADHD) sell or give away their prescribed stimulants. For a study

Specific Central Nervous System Medications Are Associated with Temporomandibular Joint Symptoms.

Aims There is evidence of association between bruxism and the increasingly common central nervous system stimulants prescribed for attention deficit hyperactivity disorder (ADHD), as well as the selective serotonin reuptake inhibitors (SSRIs) often prescribed for depression or anxiety. However, the evidence is not clear on whether these medications inducing bruxism are directly associated with temporomandibular joint disorder (TMD). The aim of this work is to evaluate whether these medications are associated with TMD symptoms. Methods Medical history and participant data were obtained for 469 patients from the University of Pittsburgh School of Dental Medicine, Dental Registry and DNA Repository, dating back to 2006. The chi-square test was used to determine any statistically significant associations. Results There were no statistically significant associations between ADHD stimulant medications or SSRIs and reported TMD symptoms. However, there were significant differences seen between specific brands of medications and reported TMD symptoms. Individuals prescribed methylphenidate (Concerta) were less likely to report temporomandibular joint discomfort (p = 0.01). Conversely, individuals prescribed citalopram (Celexa) were more likely to report temporomandibular joint discomfort (p = 0.04). Conclusion Signs and symptoms of temporomandibular joint dysfunction may be influenced by the use of certain medications prescribed for depression or attention deficit hyperactive disorder.

Attention-Deficit/Hyperactivity Disorder Medication Treatment Impact on Response to Growth Hormone Therapy: Results from the ANSWER Program, a Non-Interventional Study

To examine whether attention-deficit/hyperactivity disorder (ADHD) stimulant medication modified the linear growth response to growth hormone (GH) treatment in children enrolled in the American Norditropin Studies: Web-Enabled Research Program. Short, GH treatment-naive children with or without GH deficiency (GHD) received GH therapy. A subset also received ADHD stimulant medication (n = 1190), and others did not (n = 7230). Linear mixed models (adjusted means) examined height SDS (HSDS) and body mass index (BMI) SDS from baseline through year 4. Analyses were repeated with ADHD groups matched for baseline age, height, weight, BMI, and sex. Groups with and without GHD were compared between ADHD groups. Adjusted change in HSDS for the group receiving ADHD stimulant medication was slightly lower than that for patients not receiving stimulant medication at years 1 to 4 (P < .05). However, adjusted change in HSDS was similar between children receiving and not receiving ADHD stimulant medication when matched for baseline measurements. At year 4, 86.7% of patients receiving ADHD stimulant medication, 86.8% of total patients not receiving ADHD stimulant medication, and 84.6% of matched group patients not receiving ADHD stimulant medication achieved HSDS >-2. Year 4 adjusted change in BMI SDS was greater in the patients receiving ADHD stimulant medication compared with both groups not receiving ADHD stimulant medication (P < .05). Patients with GHD showed comparable differences in adjusted change in BMI SDS among the ADHD groups at year 4, whereas patients without GHD showed no significant differences. ADHD medication did not affect the linear growth response of children treated with GH when those receiving or not receiving ADHD stimulant medication were matched for baseline measurements. Underlying reasons for the observed greater increase in BMI in patients with GHD concomitantly treated with ADHD medication remain to be elucidated. ClinicalTrials.gov: NCT01009905.

Cardiac Autonomic Dysfunction and Arterial Stiffness among Children and Adolescents with Attention Deficit Hyperactivity Disorder Treated with Stimulants

To compare markers of cardiovascular health in youth diagnosed with attention deficit hyperactivity disorder (ADHD) by the use of stimulant medication with healthy controls. Children and adolescents (n=85; mean age 11.2±2.8years; 66 boys) diagnosed with ADHD using a stimulant and 53 siblings without ADHD (mean age 11.1±3.8years; 28 boys) were included in this cross-sectional study. Measured variables included blood pressure, heart rate (HR), HR variability: SD of the RR interval and low frequency to high frequency ratio, carotid-radial pulse wave velocity, carotid artery augmentation index (AIx), radial artery AIx, brachial artery flow-mediated dilation, and digital reactive hyperemic index. Compared with control patients, participants with ADHD had greater resting systolic blood pressure (3.9mm Hg, 95% CI [1.2-6.7], P=.005), diastolic blood pressure (5.5mm Hg, 95% CI [3.2-7.8], P<.001), HR (9.2 beats/min, 95% CI [6.0-12.3], P<.001), low frequency to high frequency ratio (0.55, 95% CI [0.22-0.89], P=.001), carotid AIx (7.2%, 95% CI [1.9-12.5], P=.008), and pulse wave velocity (0.36m/s, 95% CI [-0.05, 0.78], P=.089), and lower SD of the RR interval (-33.7milliseconds, 95% CI [-46.1, -21.3], P<.001). Neither flow-mediated dilation nor reactive hyperemic index was significantly different. Children and adolescents being treated with a stimulant medication for ADHD exhibited signs of altered cardiac autonomic function, characterized by increased sympathetic tone, and showed evidence of arterial stiffening.

Stimulant Medication for ADHD in Opioid Maintenance Treatment

Objective: The use of central stimulant medication in adults with attention deficit hyperactivity disorder (ADHD) who receive opioid maintenance treatment remains controversial and empirical evidence is limited. Because of the abuse potential of stimulant drugs, Norway has restrictions on prescribing central stimulants to individuals who have substance use disorders or who are on opioid maintenance treatment. In this naturalistic study, we describe experiences from a program through which central stimulant medication was administered to patients with ADHD receiving opioid maintenance treatment. Methods: This report is based on a program evaluation of a combined treatment project designed to provide stimulant medication to patients with adult ADHD who were receiving opioid maintenance treatment. As part of the clinical treatment, patients were monitored closely for any medical issues or adverse medication reactions and provided regular urine samples for analysis and information regarding demographics, treatment goals, legal involvement, diagnoses, substance abuse, and ADHD symptoms. Monitoring occurred at baseline, at 2 months (after patients being stabilized on the central stimulant), and again at 3, 6 and 24 months. Results: Among 42 patients initially offered the combined treatment, 24 were actually eligible, 20 started the combined treatment, and 10 stayed in the program. We were not able to identify a single major cause of treatment dropout. Patients reported significantly fewer symptoms of ADHD at the 6- to 8-week point, regardless of whether the data were analyzed using an intent-to-treat (all participants) or per-protocol (only those with complete data at all points) method. Even though self-assessed ADHD scores dropped significantly during treatment, the scores still remained fairly high, suggesting persistent functional impairment. Neither severe complications nor increase in substance abuse were observed during treatment with central stimulants. Conclusions: These findings show some promise with regard to the safety and utility of central stimulant medications for patients with ADHD who are receiving opioid maintenance treatment. Our study has methodological limitations, and systematic, well-designed clinical investigations are needed to increase the knowledge base.

The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan

No prior twin study has explored the heritability of clinically diagnosed attention deficit hyperactivity disorder (ADHD). Such studies are needed to resolve conflicting results regarding the importance of genetic effects for ADHD in adults. We aimed to estimate the relative contribution of genetic and environmental influences for clinically diagnosed ADHD across the lifespan with a specific focus on ADHD in adults. Information on zygosity and sex was obtained from 59514 twins born between 1959 and 2001 included in the nationwide population-based Swedish Twin Registry. Clinical data for ADHD diagnoses (i.e. stimulant or non-stimulant medication for ADHD) were obtained from the Swedish Prescribed Drug Register (PDR) and from the National Patient Register (i.e. ICD-10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD diagnoses using structural equation modeling with monozygotic (MZ) and dizygotic (DZ) twins. The best-fitting model revealed a high heritability of ADHD [0.88, 95% confidence interval (CI) 0.83-0.92] for the entire sample. However, shared environmental effects were non-significant and of minimal importance. The heritability of ADHD in adults was also substantial (0.72, 95% CI 0.56-0.84). This study shows that the heritability of clinically diagnosed ADHD is high across the lifespan. Our finding of high heritability for clinically diagnosed ADHD in adults indicates that the previous reports of low heritability are best explained by rater effects, and that gene-identification studies of ADHD in adults need to consider pervasiveness (e.g. multiple raters) and developmentally (e.g. childhood-onset criteria) informative data.

Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults

Objective:To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants.Methods:ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large US administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6–17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models.Results:Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28–3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73–4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically significant when compared to OROS MPH and MPH LA patients.Limitations:This study did not control for ADHD severity.Conclusion:Overall, compared to LDX-treated patients, patients initiated on other ADHD medications were equally or more likely to have a therapy augmentation and more likely to deviate from the recommended once-daily dosing regimen.

Dopamine Receptors and the Pharmacogenetics of Side-Effects of Stimulant Treatment for Attention-Deficit/Hyperactivity Disorder

There is considerable interest in the pharmacogenetics of responses to stimulant treatment for attention-deficit/ hyperactivity disorder (ADHD) (Froehlich et al. 2010). By contrast, little attention has been paid to individual differences in side effects. Dopamine function in the prefrontal cortex (PFC) is a strong candidate system for understanding these (Arnsten, 2009). D1 receptors are the most abundant dopamine (DA) receptor subtype, and mediate most of the cellular effects of DA in this region (Lewis and Gonzalez-Burgos 2006). They are thought to be involved in the regulation of sustained firing of dorsolateral PFC neurons during the delay phase of delayed-response tasks that require working memory (Sawaguchi and Goldman-Rakic 1994; Seamans and Yang 2004; Lewis and Gonzalez-Burgos 2006). Sawaguchi and Goldman-Rakic (1994) showed that D1 dopamine receptors in the dorsolateral prefrontal cortex of monkeys participated in the maintenance of internalized visuospatial representations and/or in the control of eye movements governed by internal cues. They suggested that the D1 family of dopamine receptors may have a critical role in PFC-mediated working memory and cognitive deficits. Variations in D1 polymorphism rs4532 are associated with ADHD (Bobb et al. 2005) and predict side effects to medication for schizophrenia (Potkin et al. 2003; Lai et al. 2011), although in the latter studies the effects may relate to excess dopamine at the D1 receptor. In both cases, there are good reasons to suggest that D1 receptor genetics may predict side-effects from stimulant medication for ADHD. We tested the relationship of stimulant side effects to common variations in DA receptor genes using 90 Caucasian children (79.2% males) who met formal criteria for American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnosis of ADHD (American Psychiatric Association 1994); were 4–14 years of age (mean = 8.85 years; SD= 2.32); had no major neurological/physical illness; had an intelligence quotient (IQ) >70; were using stimulant medication; and were not using another psychoactive medication (full demographic and diagnostic data and medication use available from Dr. Levy). Ethics approval and fully informed consent was from the University of New South Wales. Participants gave blood (52.5%) or saliva (or both for a smaller reliability check sample) via Oragene saliva collection kits (http://www.dnagenotek.com/). DNA extraction rates were >95% for both methods. Samples were genotyped for four dopamine receptor single nucleotide polymorphisms (SNPs): DRD1 rs4532, DRD2 rs6277, DRD3 rs6280; DRD4 rs7932167, and COMT rs4680. All were in Hardy–Weinberg equilibrium. Genotypes were determined using iPLEX Gold primer extension followed by mass spectrometry analysis on the Sequenom MassARRAY system (Sequenom, San Diego, CA) by the Australian Genome Research Facility (AGRF: http://www.agrf.org .au/). Age, weight sex, and IQ were noted, and the side effects rated as absent, mild, moderate, and severe, using a modified Barkley side-effect scale (Barkley et al. 1990). Medication usage was as follows: Primary medication Ritalin (immediate release [IR]) n = 43, dosage mean = 22.03 SD = 11.7; Ritalin (modified release) n = 14, dosage mean = 26.43 SD = 6.33; Concerta n = 12, dosage mean = 29.25 SD = 7.79; dexamphetamine n = 19, dosage mean = 8.37 SD = 4.47; dexamphetamine (long acting [Dex LA]) n = 2, dosage mean = 10 SD = 0; secondary medication Ritalin (IR) n = 5, dosage mean = 14.0 SD = 10.25; Catapres n = 9, dosage mean = 25.05 SD = 10.83. Secondary medications were distributed as follows: 4 of the 43 children receiving primary Ritalin IR were also receiving Catapres at night; 6 of the 14 children receiving Ritalin (modified release) were receiving a secondary medication, that is, 3 were also receiving Catapres at night, and 3 were receiving an additional Ritalin IR during the day. Two of the 19 children receiving dexamphetamine were also receiving Ritalin IR during the day; none of those on Dex LA were receiving an secondary medication; 2 of the 12 on Concerta were receiving Catapres at night. Medication doses were standardized to a standard Ritalin (IR) dose of 10 mg by the following formula: Dexamphetamine 5mg =Ritalin IR 10mg; Ritalin (modified release) 10mg =Ritalin IR 5mg b.i.d.; Concerta 18mg =Ritalin IR 5mg t.i.d. We reduced the 16 side effects items to factors using principal components analysis. Both parallel analysis and Velicer’s minimum average partial (MAP) test indicated that there were three nonrandom factors; therefore, we generated a three factor solution using Varimax rotation with Kaiser normalization. Factor loadings are available from Dr. Levy. The three factors, nausea, withdrawal

When the Diagnosis Is Dual

When the Diagnosis Is Dual