No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: A review of controlled and naturalistic studies
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a common disorder of childhood that often persists into adulthood. Although stimulant medications are recommended as the first-line treatment for ADHD because of their documented short-term effects in children and adults, less is known about their effects on long-term outcome in adults. Here we review the long-term efficacy and safety of the stimulant drugs methylphenidate and amphetamine, as well as the related compound atomoxetine. We performed a systematic review to identify direct and indirect effects of stimulant therapy on long-term outcome in adults. Five randomized controlled trials (RCTs), and 10 open-label extension studies of initial short-term RCTs, with total follow-up of at least 24weeks, were identified. All these RCTs found that medication was significantly more efficacious than placebo in treating ADHD in adults, and the extension studies showed that this favorable effect of medication was maintained during the open-label follow-up period. However, since the maximum duration of these pharmacological trials was 4years, we also reviewed 18 defined naturalistic longitudinal and cross-sectional studies, to provide more information about longer term functional outcomes, side effects and complications. These observational studies also showed positive correlations between early recognition of the disorder, stimulant treatment during childhood and favorable long-term outcome in adult ADHD patients. In conclusion, stimulant therapy of ADHD has long-term beneficial effects and is well tolerated. However, more longitudinal studies of long duration should be performed. In addition, the ethical issues involved in performing double blind RCTs of many years duration should be further explored.
... This is a valuable implication, both from the point of view of rank-and-file practitioners and clinical guidelines developers (of note, there has been little consensus among experts about the optimal strategies for sequential pharmacological treatments with psychostimulants and other drugs for ADHD; see Arnett and Stein 2018;Cortese 2020 andWong et al. 2019). Second: there is a dearth of longer-term trials on pharmacotherapy for ADHD in adults (an important obstacle, since the duration of the therapy in real-life settings usually reflects the chronic course of the condition [Fredriksen et al. 2013]). Third: the certainty of the evidence is relatively low (in other words, the relative effectiveness and safety of the drugs for ADHD has not been determined yet [Balshem et al. 2011]). ...
... While the legal status of psychostimulants as controlled substances is 'firmly established' (e.g., see schedule II of the U.S. Controlled Substances Act [Preuss et al. 2020]), it remains unclear whether in clinical settings MPH should be considered a 'genuine' -even if only potential -drug of abuse. Notably, the authors of the two long-term naturalistic studies did not find any significant relationship between treatment with psychostimulants (including MPH) and subsequent substance use disorders in adults with ADHD (Biederman et al. 2008;Faraone et al. 2007) (for an overview, see the article by Fredriksen et al. [2013]). This conclusion remains in line with the seminal paper by Volkow and Swanson (2003), who noticed that abuse liability of MPH depends primarily on the route of administration -with expeditious rise of DA levels, once the medication is snorted or injected (admittedly, these scenarios are very remote from the real-life context of providing treatment for patients with ADHD; see the section 'Acute toxicity' below). ...
... And while 'loose ends' are hardly unique in psychiatric research in general (Alda and Hajek 2012), there are, in our opinion, some specific aspects making it particularly challenging to get one's head around the treatment objectives in ADHD. Precisely, ADHD is an umbrella term for a set of trait-like features and a developmental trajectory alike (Asherson et al. 2016;Franke et al. 2018;Fredriksen et al. 2013). For this reason, the day-to-day adverse consequences of ADHD are not limited to various social, academic, and occupational circumstances of the individual's life (Roselló et al. 2020). ...
Rationale
Psychostimulants, including methylphenidate (MPH), are the mainstay of pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) in adults. Even though MPH is the most commonly used medication for ADHD these days, there are relatively few resources available that provide comprehensive insight into the pharmacological and clinical features of the compound.
Objective
The aim of this paper is to provide an up-to-date outline of the pharmacology and clinical utility of MPH for ADHD in adult patients.
Methods
While conducting the narrative review, we applied structured search strategies covering the two major online databases (MEDLINE and Cochrane Central Register of Controlled Trials). In addition, we performed handsearching of reference lists of relevant papers.
Results
Methylphenidate exhibits multimodal mechanism of action, working primarily as a dopamine and noradrenaline reuptake inhibitor. It also protects the dopaminergic system against the ongoing ‘wearing off’ (by securing a substantial reserve pool of the neurotransmitter, stored in the presynaptic vesicles). In placebo-controlled trials, MPH was shown to be moderately effective both against the core ADHD symptoms (standardized mean difference [SMD], 0.49; 95% confidence interval [CI], 0.35–0.64), and the accompanying emotion regulation deficits (SMD, 0.34; 95% CI, 0.23–0.45). The most common adverse events related to long-term treatment with MPH are decreased appetite (~ 20%), dry mouth (15%), heart palpitations (13%), gastrointestinal infections (~ 10%), and agitation/feeling restless (~ 10%).
Conclusions
There is substantial body of evidence to suggest that MPH is an effective and safe treatment option for adults with ADHD.
... Evidence from controlled trials for longer term benefits of stimulants and atomoxetine is largely absent. Five RCTs and ten open-label extension studies of initial short-term RCTs, with a minimum total follow-up of 24 weeks, were identified in a systematic review [33]. All of these RCTs found that medication was significantly more efficacious than placebo in treating ADHD in adults, and the extension studies suggested that this favorable effect of medication was maintained during the open-label follow-up period [33]. ...
... Five RCTs and ten open-label extension studies of initial short-term RCTs, with a minimum total follow-up of 24 weeks, were identified in a systematic review [33]. All of these RCTs found that medication was significantly more efficacious than placebo in treating ADHD in adults, and the extension studies suggested that this favorable effect of medication was maintained during the open-label follow-up period [33]. The duration of these trials was limited to a maximum of four years. ...
... Further observational studies (naturalistic longitudinal and crosssectional) provided information about longer term functional outcomes, side effects and complications. These studies also suggested positive correlations between early recognition of the disorder, stimulant treatment during childhood and favorable long-term outcome in adult ADHD patients [33]. Limitations of the currently available long-term studies include the substantial diversity of outcome measures, study designs not allowing for a meta-analytic evaluation, and the focus on ADHD symptoms as a measure of efficacy rather than on the functional implications of drug treatment. ...
Attention deficit hyperactivity disorder (ADHD) is a frequently diagnosed and treated behavioral disorder in children and adolescents and may persist into adulthood. The core symptoms of ADHD frequently cause significant impairment in academic, social and behavioral functioning over many years in children, adolescents and adults. Currently used treatments, such as pharmacotherapy and behavior therapy, can yield significant short-term benefits for many individuals with ADHD. Even though the positive therapeutic effects of medications such as methylphenidate have consistently been demonstrated in children and adults, the extent of their efficacy remains a matter of debate in view of possible bias of research studies and low quality of outcome measures. The therapeutic goals in ADHD should extend beyond the currently described treatment response and should account for the chronicity and long-term impact of the disorder, involving long-term objectives for the treatment of ADHD. The findings of drug trials assessing efficacy and safety over short time periods should be interpreted with caution and cannot be extrapolated to longterm outcomes. It is unclear whether or not the currently used treatments mitigate the negative impact of nontreatment on the quality of life of individuals with ADHD over an extended time period. Long-term randomized controlled trials (RCTs), which are the gold standard for measuring treatment effects, are largely absent and constitute a logistical and ethical challenge. In particular, there are no RCTs supporting the hypothesis that methylphenidate has a long-term “neuroprotective” impact. Long-term administration may result in a diminution of beneficial effects of the drugs used in ADHD, since the brains of individuals with ADHD become more tolerant to the neurotransmitter changes induced by medication. Scant research has adequately evaluated the long-term safety of drugs for ADHD, and systematic monitoring is needed. Possible risks of long-term medication in certain patient subgroups, such as elderly adults, have not been sufficiently investigated. Adverse consequences of ADHD medications may include serious cardiovascular events. While an increased risk of cardiovascular adverse effects is likely to be small in children and adolescents treated with ADHD medications, the risk following long-term administration and in elderly patients may be higher. The long-term safety of ADHD medications remains an open question. Poorly determined long-term beneficial effects of medication need to be carefully weighed against possible over-prescription and a range of potential adverse effects. A method for identifying patients who may obtain more benefits than harms from ADHD medication should be investigated. The close connection of the pharmaceutical industry to the clinical evaluation of ADHD medications is a matter of serious concern, since drug trials funded by industry may result in biased findings and selective reporting of results. Many alternative treatments are rendered questionable by the lack of any methodologically sound evaluation. In future, it may be worth initiating large-scale, well-designed studies investigating the effects of other treatment approaches, such as physical exercise, on ADHD. In summary, treatment of ADHD has no proven beneficial impact on long-term outcomes but may be associated with various adverse effects.
... 19 A thorough review of the safety of approved ADHD medication has been conducted elsewhere. 20 Increasingly, there is recognition that medical cannabis (MC) may offer an alternative treatment option for adult ADHD. 21 In one case report, treatment with MC revealed marked improvement of ADHD symptoms. ...
... Notably, anxiety scores were higher in the high ASRS score subgroup (median 10 [IQR 7-13]) than for the low ASRS score subgroup (4.5 [3][4][5][6][7]) (OR -0.9, 95% CI -1.5 to -0.31; P<0.01). Importantly, the low ASRS score subgroup consumed higher (28 mg) monthly CBN doses than the high (15 [12][13][14][15][16][17][18][19][20] mg) ASRS score subgroup (OR 0.58, 95% CI -0.24 to 1.4; P<0.01). However, although CBN is a metabolite of THC, we found no significant differences of monthly THC doses between the low (5000 [3400-6700] mg) and high (4600 [3200-5900] mg) ASRS score subgroups (OR 0.26, 95% CI -0.54 to 1.1; P=0.56) (Figure 6). ...
... The division into low and high ASRS score subgroups was corroborated by its associations with the ADHD rating scale scores for ADHD symptom severity. Specifically, inattentiveness, compulsivity/hyperactivity, and the total questionnaire scores were higher in the high ASRS score subgroup (14 [12][13][14][15][16][17][18][19][20], 12 [9.2-14], and 26 [23][24][25][26][27][28][29][30][31], respectively) than for the low ASRS score subgroup (9 [7][8][9][10][11], 7 [5][6][7][8][9], and 16 [12][13][14][15][16][17][18][19][20], respectively) (OR -0.97, 95% CI -1.5 to -0.39; OR -0.7, 95% CI -1.3 to -0.14; and OR -1.1, 95% CI -1.6 to -0.49; P<0.001 for all). ...
Objective: The aim of this cross-sectional questionnaire-based study was to identify associations between the doses of cannabinoids and terpenes administered, and symptoms of attention deficit hyperactivity disorder (ADHD). Methods: Participants were adult patients licensed for medical cannabis (MC) treatment who also reported a diagnosis of ADHD by a physician. Data on demographics, ADHD, sleep, and anxiety were collected using self-report questionnaires. Data collected on MC treatment included administration route, cultivator, cultivar name, and monthly dose. Comparison statistics were used to evaluate differences in reported parameters between low (20–30 g, n=18) and high (40–70 g, n=35) MC monthly dose and low adult ADHD self-report scale (ASRS, 0–5) score (i.e. ≤3.17 score, n=30) or high ASRS score (i.e. ≥3.18 score, n=29) subgroups. Results: From the 59 patients that answered the questionnaire, MC chemovar could be calculated for 27 (45%) of them. The high MC monthly dose group consumed higher levels of most phyto-cannabinoids and terpenes, but that was not the case for all of the cannabis components. The high dose consumers and the ones with lower ASRS score reported a higher occurrence of stopping all ADHD medications. Moreover, there was an association between lower ASRS score subgroup and lower anxiety scores. In addition, we found an association between lower ASRS score and consumption of high doses of cannabinol (CBN), but not with ∆-9-tetrahydrocannabinol (THC). Conclusion: These findings reveal that the higher-dose consumption of MC components (phyto-cannabinoids and terpenes) is associated with ADHD medication reduction. In addition, high dosage of CBN was associated with a lower ASRS score. However, more studies are needed in order to fully understand if cannabis and its constituents can be used for management of ADHD.
Journal name: Rambam Maimonides Medical Journal
... For example, Surman, Hammerness, Pion and Faraone (2013) [183] found support for this in their study of adults based on self reported measures. Stimulant treatment is often given when someone is first diagnosed with ADHD due to its short-term effectiveness [184]. Other studies have assessed the longer term effectiveness of specific stimulants such as methylphenidate and amphetamine for adults. ...
... Other studies have assessed the longer term effectiveness of specific stimulants such as methylphenidate and amphetamine for adults. In a recent systematic review, Fredriksen, Halmøy, Faraone and Haavik (2013) found that stimulant treatment was more effective than a placebo, including at a 24 week follow up [184]. ...
This research was commissioned by the NHS Liverpool Clinical Commissioning Group (CCG) to identify the current health needs and service provision for adults and children with neurodevelopmental conditions in Liverpool; focusing on Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorders. The findings from this report aimed to inform decisions relating to the commissioning and delivery of local services for individuals with neurodevelopmental conditions
... 26 Long-term studies of efficacy and safety in adults with ADHD are also limited, potentially contributing to the undertreatment of adults. 27 Of particular importance is the rate of nonadherence among adult patients. Overall rates of nonadherence have been found to range from 13.2% to 64.0% of patients with ADHD, but predictors of nonadherence included older age and later-onset ADHD, suggesting adherence may be a greater challenge in adult patients. ...
... 28 This result is supported by findings from long-term studies of adult ADHD, which found a high rate of nonadherence to ADHD medications, with up to 50% of adults discontinuing treatment after 2 years. 27 This trend is observed in ADHD medications of all types, including long-acting stimulants (discontinuation rate, 19.1% across all ages), short-acting stimulants (99% beyond 12 months in 6-12-year-old patients), and atomoxetine (26.0%-38.3% across all ages). ...
Background
Adults with attention-deficit/hyperactivity disorder (ADHD) often face delays in diagnosis and remain untreated, despite significant negative impacts. To evaluate the safety and efficacy of transdermal treatment options in children, adolescents, and adults, a systematic literature review was conducted, with a focus on the implications of transdermal therapies for ADHD in adults.
Methods
A MEDLINE/Embase/BIOSIS/SCOPUS database search was conducted December 4, 2019, for English-language articles of interventional clinical trials using transdermal formulations for the treatment of ADHD without publication date limit. Assessed outcomes included efficacy, safety, adherence, abuse potential, cost efficacy, and health-related quality of life.
Results
Of 23 eligible publications, 18 were in children or adolescents (n = 1699; range 23-305), and 5 in adults (n = 274; range 14-90); all included methylphenidate transdermal system (MTS). All seven pediatric publications reporting change in ADHD symptomology from baseline reported a significant improvement with MTS treatment. Similarly, in three adult publications, ADHD symptoms improved significantly with MTS treatment. Safety findings in pediatric and adult studies were comparable; the most frequently reported treatment-emergent adverse events (TEAEs), namely, headache, decreased appetite, and insomnia, were reported in 13/16 (81%) of publications reporting specific TEAEs. MTS-related dermal reactions were mostly mild and transient. Discontinuation due to dermal reactions was reported in 10 studies (range 0%-7.1% [1 of 14 patients]). MTS compliance was high when assessed (97%-99%).
Conclusions
Transdermal therapies provide a useful treatment formulation for ADHD. Studies of MTS and other transdermal formulations, such as amphetamine, in adult patients are needed in this underserved population.
... The lower risk for all-cause mortality may be linked to other benefits of physical activity through reduced cardiovascular risk (i.e., improved exercise capacity) and reduced risk for other comorbidities" [59]. Nevertheless, currently, there is insufficient information to support specific recommendations related to the domain, optimal dose and timing of activity that could contribute to the dose of 10-15 METs hours per week in postmenopausal women with breast cancer [15,57,60]. The evidence highlights the importance of breast cancer survivors engaging in any amount of physical activity they can, increasing their activity level when possible, and especially not decreasing physical activity after their diagnosis and treatment [15]. ...
This study examines both the effect of a twice-weekly combined exercise—1 h session of strength and 1 h session of impact-aerobic—on body composition and dietary habits after one year of treatment with aromatase inhibitors (AI) in breast cancer survivors. Overall, forty-three postmenopausal women with a BMI ≤ 35 kg/m2, breast cancer survivors treated with AI, were randomized into two groups: a control group (CG) (n = 22) and a training group (IG) (n = 21). Body composition, i.e., abdominal, visceral, and subcutaneous adipose tissue) was measured by magnetic resonance. In addition, some questionnaires were used to gather dietary data and to measure adherence to the Mediterranean diet. After one year, women in the IG showed a significant improvement in body composition, indicated by decreases in subcutaneous and visceral adipose tissue, and total fat tissue. Furthermore, the dietary habits were compatible with moderate adherence to the Mediterranean diet pattern and a low dietary intake of Ca, Zn, Folic Ac, and vitamins D, A, and E. A twice-weekly training program combining impact aerobic exercise and resistance exercise may be effective in improving the body composition for postmenopausal women who have breast cancer treated with AI, and the results suggest the need for nutritional counselling for this population.
... Les adultes avec TDAH présentent en moyenne un niveau d'étude plus faible que des pairs sans TDAH DuPaul et al., 2009;Frazier et al., 2007). Ils comptabilisent davantage de jours d'absence au travail, sont plus souvent licenciés et changent fréquemment d'emploi (Adamou et al., 2013;Fredriksen et al., 2013;Mannuzza & Klein, 2000;Murphy & Barkley, 1996;Secnik et al., 2005). Sur le plan interpersonnel, les relations familiales sont marquées par une prévalence plus élevée de maltraitance et de rejet (Brod et al., 2012). ...
Le surplus de pensées et la dysrégulation émotionnelle (DE) sont deux expressions cliniques sous-évaluées dans le Trouble du Déficit de l’Attention avec ou sans Hyperactivité (TDAH) de l’adulte. Bien que qu’ils ne soient pas spécifiques au TDAH, ces deux symptômes sont pourtant au coeur des plaintes des patients. L’objectif de ce travail de thèse était de reconsidérer le tableau clinique du TDAH de l’adulte en investiguant les particularités psychopathologiques et cognitives des symptômes de surplus de pensées et de DE. Pour cela, différents auto-questionnaires ainsi qu’une évaluation cognitive comprenant la tâche de fluences verbales ont été proposés à des adultes avec TDAH. Sur le plan psychopathologique, le surplus de pensées et la DE représentent des caractéristiques centrales de la présentation clinique du TDAH de l’adulte, indépendantes d’un trouble de l’humeur associé. De plus, ces deux symptômes sont fortement associés et entretiennent des liens étroits avec l’arousal. Sur le plan cognitif, le surplus de pensées et la DE sont sous-tendus par des atypies du fonctionnement exécutif.
... Pharmacological treatment for ADHD has repeatedly been shown to reduce ADHD symptoms in several short-term randomized controlled trials [50]. However, limited studies have evaluated pharmacotherapy's long-term effects on these individuals' clinical and functional outcomes in real-life settings [51,52]. Our findings align with studies showing that pharmacotherapy for ADHD improves functional impairments caused by ADHD [34]. ...
Background:
Substance use disorders (SUDs) are a considerable public health problem. Attention-deficit/hyperactivity disorder (ADHD) frequently occurs in patients with SUD. Several studies demonstrated that ADHD constitutes a significant risk factor for the development of SUDs and suggest that childhood ADHD pharmacotherapy might help prevent development of SUD.
Objectives:
The study aimed to explore the effect of childhood ADHD pharmacotherapy on later life's functional impairment and substance use patterns.
Methods:
Treatment-seeking SUD patients with ADHD (n = 52) were recruited from various rehabilitation facilities in South Africa. Adult ADHD individuals without SUD (n = 48) were recruited from clinicians, retail pharmacies, and the general public. SUD participants in rehabilitation facilities were screened for and diagnosed with ADHD. Lifetime substance use was assessed using self-report. ADHD-related functional impairment was assessed by the Weiss Functional Impairment Rating Scale (WFIRS). Information on present and lifetime use of ADHD medication was obtained. Clinical outcomes between those with and without a history of ADHD pharmacotherapy were compared.
Results:
Medicated participants (n = 59) showed lower levels of ADHD-related impairment across all functional domains (p < 0.001), compared to non-medicated participants (n = 41). They also consumed less alcohol (p = 0.04), cannabis (p < 0.001), and illicit drugs (p = 0.006) compared to the non-medicated group. Furthermore, medicated participants had a lower frequency of tobacco use compared to non-medicated participants (p = 0.04). ADHD patients without SUD also more often received medication (100% vs. 18.6%; p < 0.001) and for a longer time (121.10 vs. 9.52 months; p < 0.001).
Conclusion:
Childhood ADHD pharmacotherapy might be associated with a decreased risk for substance use in adulthood and lower ADHD-related impairment. Despite study limitations, these findings underline the importance of early ADHD detection and treatment, which might prevent SUD.
... In case of a sufficient treatment response, regular treatment should be continued for at least 12 months. Longitudinal studies have shown that treatment lasting for several years can be rated as superior concerning symptom reduction and improvement of daily functioning compared to shorter therapy durations (Fredriksen et al. 2013). However, also in patients undergoing long-term treatment, it is reasonable to interrupt treatment from time to time in order to reevaluate the indication of stimulant treatment. ...
Besides psychosocial interventions, like psychoeducation and specific psychotherapeutic treatments, e.g., cognitive-behavioral therapy, pharmacological treatments present a key element within the overall therapeutic concept of attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults. Currently, three different pharmacological agents are approved by federal agencies in Germany for the treatment of ADHD in adults. As stimulants, delayed release methylphenidate and lisdexamfetamine can be prescribed. Efficacy and tolerance of both agents can be considered as good. Alternatively, atomoxetine can be prescribed, which does not belong to the stimulants and whose efficacy and tolerance can be considered as good as well.
... Atomoxetine is the main non-stimulant drug that is recommended for treatment of ADHD in adults (Bolea-Alamañac et al., 2014). Clinical efficacy of stimulants and atomoxetine are comparable (Bolea-Alamañac et al., 2014;Shang et al., 2016) in adult ADHD (Durell et al., 2013;Fredriksen et al., 2013) and pediatric ADHD (Cheng et al., 2007), although they cannot be considered similar because they have differences in their mechanisms of action and hazards (Spencer et al., 1998;Bolea-Alamañac et al., 2014). Atomoxetine is preferred if there are any contra-indications to stimulant treatment, such as if methylphenidate is ineffective or not tolerated, presence of anxiety disorder or tics, and risk of misuse or diversion (Bolea-Alamañac et al., 2014). ...
For decades, psychostimulants have been the gold standard pharmaceutical treatment for attention-deficit/hyperactivity disorder (ADHD). In the United States, an astounding 9% of all boys and 4% of girls will be prescribed stimulant drugs at some point during their childhood. Recent meta-analyses have revealed that individuals with ADHD have reduced brain volume loss later in life (>60 y.o.) compared to the normal aging brain, which suggests that either ADHD or its treatment may be neuroprotective. Crucially, these neuroprotective effects were significant in brain regions (e.g., hippocampus, amygdala) where severe volume loss is linked to cognitive impairment and Alzheimer’s disease. Historically, the ADHD diagnosis and its pharmacotherapy came about nearly simultaneously, making it difficult to evaluate their effects in isolation. Certain evidence suggests that psychostimulants may normalize structural brain changes typically observed in the ADHD brain. If ADHD itself is neuroprotective, perhaps exercising the brain, then psychostimulants may not be recommended across the lifespan. Alternatively, if stimulant drugs are neuroprotective, then this class of medications may warrant further investigation for their therapeutic effects. Here, we take a bottom-up holistic approach to review the psychopharmacology of ADHD in the context of recent models of attention. We suggest that future studies are greatly needed to better appreciate the interactions amongst an ADHD diagnosis, stimulant treatment across the lifespan, and structure-function alterations in the aging brain.
... The severity of impairments in verbal memory and psychomotor function for methamphetamine users were correlated with the loss of dopamine transporters in the striatum and nucleus accumbens [14,15]. Atomoxetine, a cognitive enhancer, is marketed for Attention-Deficit/Hyperactivity Disorder (ADHD) and is a generally well-tolerated and efficacious treatment for ADHD across prolonged treatment [16,17]. Rabiey et al. [18] demonstrated that atomoxetine has appropriate efficacy in suppressing methamphetamine craving and possible potential effects on its treatment. ...
Background: A substantial body of evidence indicates that methamphetamine abuse can lead to persistent and severe cognitive dysfunction. Preclinical studies and early pilot clinical investigations suggested that atomoxetine, a cognitive enhancer, may improve cognitive dysfunction. The present study evaluated whether atomoxetine would affect cognitive dysfunction in methamphetamine-dependent patients. Methods: Participants with methamphetamine dependence (N=86) under Methadone Maintenance Therapy (MMT) were enrolled in a double-blind, placebo-controlled, randomized clinical trial. This investigation was performed on 86 subjects to consume either 40 mg/day atomoxetine (n=45) or placebo (n=41) for 8 weeks. Between January 2016 and June 2017, volunteers were selected from methamphetamine abusers in MMT centers in Kashan City, Iran. They completed the Cognitive Abilities Questionnaire at the first and each monthly visit to assess the cognitive functions. The collected data were analyzed using the Independent Samples t-test, Mann Whitney U test, and Chi-square in SPSS software. Results: This study revealed that atomoxetine treatment improved some cognitive dysfunctions in methamphetamine users, including memory, inhibitory control, selective attention, decisionmaking, planning, sustained attention, and cognitive flexibility in methamphetamine users (P<0.05); however, social cognition improvement was less than others (P=0.107). There were only mild adverse effects in the placebo and atomoxetine groups. Conclusion: The obtained findings indicated the efficacy of atomoxetine for improving cognitive dysfunction in metham
... Atomoxetine, a cognitive enhancer, is marketed for ADHD and has been shown to be a generally well-tolerated and efficacious treatment for ADHD across prolonged treatment (16,17). In the study by Rabiey et al. (18), demonstrated that atomoxetine appropriate efficacy in suppressing methamphetamine craving and possible potential effects on its treatment. ...
Background: A substantial body of evidence indicates that methamphetamine abuse can lead to persistent and severe cognitive dysfunction. Preclinical studies and early pilot clinical investigations suggested that atomoxetine, a cognitive enhancer, may improve cognitive dysfunction. The present study evaluated whether atomoxetine would affect cognitive dysfunction in methamphetamine-dependent patients.
Methods: Participants with methamphetamine dependence (N=86) under Methadone Maintenance Therapy (MMT) were enrolled in a double-blind, placebo-controlled, randomized clinical trial. This investigation was performed on 86 subjects to consume either 40 mg/day atomoxetine (n=45) or placebo (n=41) for 8 weeks. Between January 2016 and June 2017, volunteers were selected from methamphetamine abusers in MMT centers in Kashan City, Iran. They completed the Cognitive Abilities Questionnaire at the first and each monthly visit to assess the cognitive functions. The collected data were analyzed using the Independent Samples t-test, Mann Whitney U test, and Chi-square in SPSS software.
Results: This study revealed that atomoxetine treatment improved some cognitive dysfunctions in methamphetamine users, including memory, inhibitory control, selective attention, decision-making, planning, sustained attention, and cognitive flexibility in methamphetamine users (P
... Pharmacological treatment has been shown to be effective in reducing the core symptoms of ADHD (Cortese, 2020). However, medication does not help everyone (Faraone & Buitelaar, 2010) and is associated with side effects such as irritability, sleep disturbance, nervousness and reduced appetite (Cortese, 2020;Fredriksen, Halmøy, Faraone & Haavik, 2013). Some uncertainty remains about the long-term effects of ADHD medication and the need to monitor blood pressure and growth has been emphasized (Graham, Banaschewski, Buitelaar et al., 2011). ...
Psychoeducation is regarded as a first line of intervention for attention‐deficit/hyperactivity disorder (ADHD). Previous studies have been limited to psychoeducation for adult patients or parents of children with ADHD. Therefore, the aim of the present study was to investigate the acceptability and effectiveness of a psychoeducational group intervention for children with ADHD. The two‐session psychoeducational intervention, SKILLS, was completed by 125 children (6–12 years) with ADHD and their parents. Self‐ratings and parental ratings of ADHD symptoms, functional impairment and attitudes to diagnosis and treatment were collected before and after treatment. Post‐treatment client satisfaction and parental responses to an open question about SKILLS were assessed. The data were analyzed using a combination of quantitative and qualitative (content analysis) methods. A majority of the participants expressed satisfaction with the group intervention. The intervention had no effect on symptoms and level of function, although the parents were more positive to their child’s diagnosis after the intervention. The parents were positive to the group format and to the opportunity for their children to meet other children with similar symptoms. Parents wished for more interactive elements and more opportunities for children to share experiences. We concluded that the group intervention was accepted by most participants, although more activating exercises and opportunities for interaction between participants should be included. Since the intervention group was not compared with a control group, the results should be interpreted with caution. Future studies should use a randomized control treatment design and investigate the effect on adherence to later treatment.
... Bari and Robbins 2013). Collectively, the above findings from both animal experiments and clinical studies suggest that the NE system plays a vital role in the regulation of attention and impulsivity, and NE-related drugs are widely used in the treatment of ADHD with significant efficacy (Clemow et al. 2017;Fredriksen et al. 2013). ...
RationaleNoradrenaline (NE) is closely related to attentive performance and impulsive control. However, the potential sex differences regarding attention and impulsivity under the noradrenergic modulation have been largely neglected. Therefore, our study aimed to investigate whether male and female rats exhibit differential responses to NE-related drugs during the five-choice serial reaction time task (5CSRT).Methods
Male and female rats were trained in 5CSRT and administered with different NE drugs after obtaining stable baseline performance: atipamezole, a highly selective α2 receptor antagonist; prazosin, an α1 receptor antagonist; and atomoxetine, a selective NE reuptake inhibitor. Later, prazosin was selected to co-administration with atomoxetine.ResultsMale and female rats exhibited equal learning speed, and no significant baseline differences were found as measured by the 5CSRT. Atomoxetine decreased premature responses in both sexes, but the extent of this reduction was different, with the reduction greater in males. Besides, atomoxetine (1.8 mg/kg) increased the error of omissions in females. The high dose of prazosin (0.5 mg/kg) decreased the accuracy only in male rats, but this was ameliorated by the co-administration with atomoxetine.Conclusions
Atomoxetine showed significant improvement in impulsivity, but atomoxetine had less beneficial effects on impulsive control in females than in males, and it even impaired attentional performance in female rats. The α1 receptors were mainly responsible for NE drug-related sex differences in attention rather than impulsivity. The results obtained in this study indicate that the sex differences exist in both attention and impulsivity by the modulation of noradrenaline and raise the concern to improve sex-specific treatments.
... In case of a sufficient treatment response, regular treatment should be continued for at least 12 months. Longitudinal studies have shown that treatment lasting for several years can be rated as superior concerning symptom reduction and improvement of daily functioning compared to shorter therapy durations (Fredriksen et al. 2013). However, also in patients undergoing long-term treatment, it is reasonable to interrupt treatment from time to time in order to reevaluate the indication of stimulant treatment. ...
... La evidencia de la efectividad y seguridad a largo plazo, tanto del tratamiento farmacológico como del no farmacológico, sigue siendo tan escasa e inconsistente que no es concluyente 161,162 . ...
... Arrears per month remained constant in the 2 years preceding and following new prescriptions. These findings are consistent with recent longitudinal studies indicating modest effects of medication on functional outcomes among those with ADHD (9,33), despite significant concurrent and long-term reductions in core ADHD symptoms such as hyperactivity and inattention (34,35). Of note, although reduced criminal behavior on November 29, 2020 http://advances.sciencemag.org/ ...
Attention-deficit/hyperactivity disorder (ADHD) exerts lifelong impairment, including difficulty sustaining employment, poor credit, and suicide risk. To date, however, studies have assessed selected samples, often via self-report. Using mental health data from the entire Swedish population ( N = 11.55 million) and a random sample of credit data ( N = 189,267), we provide the first study of objective financial outcomes among adults with ADHD, including associations with suicide. Controlling for psychiatric comorbidities, substance use, education, and income, those with ADHD start adulthood with normal credit demand and default rates. However, in middle age, their default rates grow exponentially, yielding poor credit scores and diminished credit access despite high demand. Sympathomimetic prescriptions are unassociated with improved financial behaviors. Last, financial distress is associated with fourfold higher risk of suicide among those with ADHD. For men but not women with ADHD who suicide, outstanding debt increases in the 3 years prior. No such pattern exists for others who suicide.
... The use of the ICF framework emphasizes the intersection between individuals' abilities and the impact of the specific context on individual functioning in identifying real-life challenges (Castro & Pinto, 2013). These core sets comprehensively highlight a range of categories related to function, from activities of daily living, social relationships, academic achievement, occupational functioning, and self-care (Arnold, Hodgkins, Kahle, Madhoo, & Kewley, 2015;Fredriksen, Halmoy, Faraone, & Haavik, 2013;Hoza, 2007;Michielsen et al., 2015), underscoring the recognition of functional problems in daily life as the reason for the initial referral to services, as well as the focus of interventions (Bölte et al., 2018). ...
Children with Attention Deficit Hyperactivity Disorder (ADHD), a neurobehavioral disorder prevalent in childhood, demonstrate a persistent pattern of inattention and hyperactive and/or impulsive behavior that is more severe than their typically developing peers. Much of this challenging behavior is observed in the classroom. However, current literature on ADHD for school-aged children largely examines issues of clinical diagnosis and pharmacological management. Consequently, the associated challenges in functional limitations and participation restrictions that these children demonstrate have not been well examined. Fortunately, as members of the school-based team, occupational therapists are uniquely suited to address this important perspective. Therefore, the purpose of this study was to 1) identify the scope of occupational therapy (OT) practices in assessment, intervention and service delivery with children/youth with ADHD across Canada, 2) indicate potential research and practice gaps, and 3) discuss future implications with respect to OT intervention for children with ADHD. A bilingual national survey was created based on a comprehensive literature review and consultation with experts in pediatrics and knowledge translation. The survey link was sent to pediatric occupational therapists across Canada through mailing lists obtained from national and provincial organizations. A total of 172 surveys were completed (response rate = 10%). The majority of respondents reported that children with ADHD comprised 26–75% of their caseloads. More than 90% of respondents reported using OT interventions to address skills related to impairments (sensory processing), activity (fine motor function), and participation (school functioning) in their treatment of children with attentional disorders. OTs frequently reported using sensory-based principles to address the behavioral symptoms of children with ADHD. The most common form of service delivery was individualized sessions, followed by consultation. Potential gaps and implications at the research, practice and organizational levels are discussed to further support the role of OT with school-aged children with ADHD.
... Medication is safe and effective, with 70% of patients reporting improvement compared to 7% of controls (Fields et al. 2017;Spencer et al. 2001). As a consequence, this is perhaps the reason that the majority of research has tended to focus on the efficacy of the different classifications of medications available rather than non-pharmacological interventions (Fredriksen et al. 2013;Mészáros et al. 2009;Ravishankar et al. 2016;Wilens et al. 2001). Subsequently, for clinicians wanting to employ psychological interventions, such as Cognitive Behavioral Therapy (CBT) for example, they have a more limited evidence base when compared with interventions available for mood and anxiety disorders for instance (Sprich et al. 2012). ...
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, characterized by symptoms of inattention, hyperactivity and or impulsivity. First line treatment is medication; however, medication alone may not provide sufficient functional improvement for some patients, or be universally tolerated. A recent surge in research to treat ADHD using non-pharmacological interventions demands a comprehensive, systematic review of the literature. The aim of this review was to examine the evidence base for psychological treatments for ADHD management in adulthood. A systematic search of PsycINFO, MEDLINE, CINAHL, AMED, PubMed, and EMBASE was undertaken until January 2019 for peer-reviewed articles exploring psychological interventions for adults (18 years with no upper limit) diagnosed with ADHD. A total of 53 papers were identified for inclusion. Collectively, 92% of studies (employing various non-pharmacological interventions) found a variant of significant positive effect on either primary or secondary outcomes associated with ADHD. The strongest empirical support derived from Cognitive Behavioral Therapy interventions. In addition, findings indicated support for the effectiveness of Mindfulness, Dialectical Behavior Therapy and Neurofeedback. Other types of interventions also demonstrated effectiveness; however, support was limited due to lack of available research and methodological rigor. Psychological interventions should be considered a valid and useful addition to clinical practice. Implications and areas for future research are discussed.
... Currently, medication is the first-line treatment recommended to improve cognitive functioning, including WM, and ADHD symptoms. Both stimulants (amphetamines and methylphenidate) and nonstimulants (atomoxetine, clonidine, and guanfacine) are used for the purpose (Fredriksen, Halmøy, Faraone, & Haavik, 2013;Strand et al., 2012;Tamminga, Reneman, Huizenga, & Geurts, 2016). ...
This study examine the effects of the Cogmed training program among youths 7 to 13 years old, while controlling presence and presentation of ADHD‐related comorbidity. Participants were under pharmacological treatment for ADHD. They were randomized into an experimental group that received the Cogmed program and an active control group. They were evaluated at three time points: six weeks prior to intervention onset (T1), immediately prior to onset (T2), and one week following intervention completion (T3). Cognitive training did not lead to a reduction in ADHD symptoms or to an improvement in cognitive functions or in academic achievement.The fact that participants were on medication at time of training and evaluation normalized their performances and limited the detection of effects. The results of this study do not demonstrate the effectiveness of the Cogmed program for youths with ADHD combined type and a comorbidity when training is received while medicated. This article is protected by copyright. All rights reserved.
... Currently, medication is the first-line treatment recommended to improve cognitive functioning, including WM, and ADHD symptoms. Both stimulants (amphetamines and methylphenidate) and nonstimulants (atomoxetine, clonidine, and guanfacine) are used for the purpose (Fredriksen, Halmøy, Faraone, & Haavik, 2013;Strand et al., 2012;Tamminga, Reneman, Huizenga, & Geurts, 2016). ...
The primary objective of this study was to examine the effects of the Cogmed training program on working memory among youths 7 to 13 years old, with ADHD type and comorbidity controlled for. A secondary objective was to examine the generalization of effects to ADHD symptoms, non‐verbal reasoning, attentional and executive functions, inhibition, reading comprehension, and mathematical reasoning. Participants were under pharmacological treatment for ADHD combined type and a comorbidity. They were randomized into an experimental group that received the Cogmed program and an active control group that received a low‐intensity comparison version of the training. They were evaluated at three time points: six weeks prior to intervention onset (T1), immediately prior to onset (T2), and one week following intervention completion (T3). Results indicate no significant effect attributable to the Cogmed program. The fact that participants were on medication at time of training and evaluation normalized their performances and limited the detection of effects. Moreover, cognitive training did not lead to a reduction in ADHD symptoms or to an improvement in the other cognitive functions measured or in academic performance. The results of this study do not demonstrate the effectiveness of the Cogmed program for youths with ADHD combined type and a comorbidity when they receive the training while under pharmacological treatment.
... Randomised controlled studies have shown that pharmacotherapy reduces the ADHD symptom burden [16] and observational studies have reported that it improves important life outcomes, such as academic performance [17], social functioning [18,19] and the rate of motor vehicle accidents [20]. Nonetheless, the current pharmacological treatment of ADHD is not curative and, although many patients improve markedly, optimal outcomes are difficult to achieve, especially with regards to signs of executive dysfunction and emotional dysregulation [21,22]. ...
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder with only symptomatic care available. Genome-wide association (GWA) studies can provide a starting point in the search for novel drug targets and possibilities of drug repurposing. Here, we explored the druggable genome in ADHD by utilising GWA studies on ADHD and its co-morbid conditions. First, we explored whether the genes targeted by current ADHD drugs show association with the disorder and/or its co-morbidities. Second, we aimed to identify genes and pathways involved in the biological processes underlying ADHD that can be targeted by pharmacological agents. These ADHD-associated druggable genes and pathways were also examined in co-morbidities of ADHD, as commonalities in their aetiology and management may lead to novel pharmacological insights. Strikingly, none of the genes encoding targets of first-line pharmacotherapeutics for ADHD were significantly associated with the disorder, suggesting that FDA-approved ADHD drugs may act through different mechanisms than those underlying ADHD. In the examined druggable genome, three loci on chromosomes 1, 4 and 12 revealed significant association with ADHD and contained nine druggable genes, five of which encode established drug targets for malignancies, autoimmune and neurodevelopmental disorders. To conclude, we present a framework to assess the druggable genome in a disorder, exemplified by ADHD. We highlight signal transduction and cell adhesion as potential novel avenues for ADHD treatment. Our findings add to knowledge on known ADHD drugs and present the exploration of druggable genome associated with ADHD, which may offer interventions at the aetiological level of the disorder.
... 47 In many patients, pharmacologic treatment (usually given in combination with nonpharmacologic interventions) is effective in reducing ADHD symptoms. 45,48,49 However, not all patients respond well to medication (one study estimated efficacy of stimulant medication around 70% 50 ) or may not tolerate adverse effects. 45,51 Nonpharmacologic Interventions for Attention Deficit Hyperactivity Disorder Nonpharmacologic treatments generally have smaller effect sizes compared with pharmacologic treatment, but may be very important for those patients who do not respond well to medication 52,53 or those who present with adverse effects. ...
Genetic and environmental factors play a role in the cause and development of attention-deficit/ hyperactivity disorder (ADHD). Recent studies have suggested an important role of the gut-brain axis (GBA) and intestinal microbiota in modulating the risk of ADHD. Here, the authors provide a brief overview of the clinical and biological picture of ADHD and how the GBA could be involved in its cause. They discuss key biological mechanisms involved in the GBA and how these may increase the risk of developing ADHD. Understanding these mechanisms may help to characterize novel treatment options via identification of disease biomarkers.
Using the following link (https://authors.elsevier.com/a/1ZUyR3AL6MDLaQ) before September 21, 2019 will take you directly to the final version of our article on ScienceDirect.
... Stimulant medications for Attention-Deficit/Hyperactivity Disorder (ADHD), amphetamines and methylphenidate, are among the most researched and acutely efficacious psychoactive medication treatments in behavioral health. 1,2 They are also classified by the U.S. ...
Objectives:
To address increasing rates of stimulant misuse in college students, this study developed an evidence-based, brief clinical practice intervention for primary care providers (PCPs) to reduce stimulant medication diversion among young adults with ADHD.
Methods:
College students (N-114; 18-25 years; 68% attending universities; 24% attending community college) treated for ADHD with a stimulant and their PCPs across six practices participated in this initial, uncontrolled study of pre- to post-intervention change. An educational workshop providing strategies aimed at reducing stimulant diversion was developed and delivered to providers and staff across all practices (50% pediatric; 50% family medicine). Patients and providers completed baseline and post intervention surveys.
Results:
Diversion was relatively infrequent, 16.7% at baseline and 14.9% post-intervention, respectively. Statistically significant decreases from baseline to post-intervention were found for three diversion risk factors: (1) number of times approached to divert, (2) intent to share, sell, or trade stimulants, and (3) disclosure of stimulant use. Providers and staff reported mostly high satisfaction with the training.
Conclusions:
This study provides initial evidence for a PCP-delivered intervention to reduce stimulant diversion. Research is needed on the efficacy of targeting college students directly, working with pharmacies and student health centers, and preventing misuse among teenagers.
... The stimulants are believed to exert their effect on the catecholaminergic systems, as they amplify the actions of dopamine and norepinephrine (del Campo, Chamberlain, Sahakian, & Robbins, 2011). The stimulant methylphenidate (MPH) is a cornerstone in pharmacological treatment of ADHD in adults (Faraone & Glatt, 2010;Fredriksen, Halmoy, Faraone, & Haavik, 2013) and the majority of the MPH treatment studies have indicated improvement on at least some aspect of CPT performance (Riccio et al., 2001). Although the responses on the CPT appear to be somewhat task and dose dependent, the majority of studies indicate that RT is decreased and less variable after stimulant medication (Losier et al., 1996). ...
Objective: The aim of this study was to examine whether reaction time parameters in adult patients with ADHD could predict their response to methylphenidate (MPH). Method: Previously unmedicated patients (N = 123) were administered the Conners’ Continuous Performance Test II (CPT II) at baseline and after 6 weeks of treatment with immediate-release MPH. In addition to traditional CPT measures, we extracted intraindividual raw data and analyzed time series using linear and nonlinear mathematical models. Results: Clinical responders, assessed with the Clinical Global Impression-Improvement scale, showed significant normalization of target failures, reduced variability and skewness, and increased complexity of reaction time series after 6 weeks of treatment, while nonresponders showed no significant changes. Prior to treatment, responders had significantly higher variability and skewness, combined with lower complexity, compared with nonresponders. Conclusion: These results show that the CPT test is useful in the evaluation of treatment response to MPH.
... This first asks whether a treatment of a disorder is worthwhile when compared against alternatives in terms of allocation of healthcare funds, and second which ADHD intervention brings the most benefit at the lowest cost. For the former, an argument can be made that adult ADHD is a condition which is cost effective to treat from the societal perspective because of the efficacy and relatively low cost of the medicines used for its treatment [224,338]. For the latter, among children and adolescents with ADHD, there is consistent evidence [339][340][341][342][343] that pharmacotherapies are cost effective compared with no treatment or behavioral therapy [344]. ...
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
Objective:
The aim of this study was to evaluate growth trajectories in stimulant-exposed and stimulant-unexposed children using electronic medical record data from a large health care organization attending to moderating effects of the magnitude of exposure to stimulants, sex, and race.
Methods:
Weight, height, body mass index (BMI), prescription, and sociodemographic information were extracted from the electronic medical records of a large health care organization. Included were children who were 6 to 12 years at the time they were receiving stimulants with a concurrent growth assessment (index assessment) plus 1 to 4 years of additional growth assessments thereafter. Non-attention-deficit/hyperactivity disorder (ADHD) children who were unexposed to stimulants were age and sex matched to those exposed. Stimulant exposure was examined as the total number of months with stimulant prescriptions, percentage of follow-up time exposed to stimulants, and cumulative stimulant dose.
Results:
Our sample consisted of 323 children exposed to stimulants with available growth data and 1615 unexposed children. Small but significant decreases in height trajectories were found over time in exposed children compared with those unexposed. Weight and BMI trajectories decreased in the first year of follow-up with stabilization and increased thereafter. Growth trajectory effects were largest in girls (height, weight, and BMI), White children (weight), and children with more total stimulant exposure (weight).
Conclusion:
This comprehensive analysis of an ecologically informative sample attending to key covariates of the magnitude of exposure to stimulants, sex, and race extends previous findings, showing that effects on growth trajectories are small and do not appear to pose a significant clinical concern for most children with ADHD treated with stimulants from childhood onto adolescent years.
The second volume of Behavioral Genetics of the Mouse provides a comprehensive overview of the major genetically modified mouse lines used to model human neurobehavioral disorders; from disorders of perception, of autonomous and motor functions to social and cognitive syndromes, drug abuse and dependence as well as neurodegenerative pathologies. Mouse models obtained with different types of genetic manipulations (i.e. transgenic, knockout/in mice) are described in their pathological phenotypes, with a special emphasis on behavioral abnormalities. The major results obtained with many of the existing models are discussed in depth highlighting their strengths and limitations. A lasting reference, the thorough reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
At the end of the twentieth century, there were great expectations that neuroscience discoveries catalyzed by the Decade of the Brain would result in enhanced clinical practices for treatment and prevention of Attention-Deficit/Hyperactivity Disorder (ADHD) or Hyperkinetic Disorder (HKD), which were summarized by an international collaborative group of child psychologists and psychiatrists (Swanson JM, Sergeant J, Taylor E, Sonuga-Barke EJS, Jensen PS, Cantwell DP: Lancet 351:429–433, 1998). Based on five topics (diagnosis, epidemiology, treatment, prognosis, and pathophysiology), we suggested that “brain imaging studies implicate the frontal basal-ganglia neural networks,” “molecular genetic studies implicate the dopamine pathways that modulate and integrate neural activity of these networks,” and “neuroanatomical and biochemical abnormalities provide firm ground to build an understanding of the biological bases of ADHD/HKD.” Almost 20 years later, the collaborative group was reconvened (Swanson JM, Sergeant JA, Taylor EA, Sonuga-Barke EJS, Jensen PS, Castellanos FX: Chapter 142: attention deficit hyperactivity disorder. In: Pfaff DW, Volkow ND (eds) Neuroscience in the 21st century. Springer, New York, 2016) and prepared a chapter for the second edition of Neuroscience in the twenty-first Century. During the beginning of the twenty-first century, we noted progress was made, but problems emerged that muted the previous hopes and expectations. We concluded “the underlying pathophysiology of ADHD is much more complex than suggested by research from the twentieth century,” “ADHD is not a unitary condition and instead is a final common pathway of many underlying biologic and environmental factors,” and “research should clarify these factors and enable the refinement of available intervention and the development of new interventions for ADHD across the life span.” For this revision, we reconstituted the group to provide another update based on the same five topics that were addressed previously. Brief reviews are provided to summarize the (a) revisions to the official diagnostic criteria that define essential features of the modern disorder, (b) estimates of the administrative prevalence in different countries of the recognized disorder, (c) trends in use of stimulant and non-stimulant medications for treatment of the symptomatic disorder, (d) expectations of the course of the neurodevelopmental disorder, and (e) speculations about the biological and environmental causes of the complex disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a common developmental disorder of the brain with the essential features of a persistent pattern of age-inappropriate inattention and/or hyperactivity–impulsivity. The symptom-based diagnosis of ADHD in elite athletes is not different from that of ADHD in the general population. However, athletes’ fame and advanced athletic skills can be obstacles to diagnosis by clinicians. ADHD symptoms can negatively affect sports performance, while ADHD may play a salient role in the choice of both sport as a career and competition at the elite level. Stimulants are the primary pharmacological treatment for ADHD in the general population and in elite athletes. Atomoxetine is the first-line medication for the treatment of ADHD among sports psychiatrists. The management of ADHD should focus on psychosocial interventions with or without medication to optimize long-term outcomes for elite athletes in sports and in life.KeywordsElite athleteAttention-deficit/hyperactivity disorderStimulantPsychosocial intervention
Objective
Adult Attention Deficit Hyperactivity Disorder (ADHD) is internationally well described but little clinical information has emerged from Australia. We explored the demographic and psychiatric characteristics of adults consecutively referred to an Australian private psychiatric clinic.
Methods
Medical records of 473 adults aged 18–70 with ADHD were reviewed with the Adult Self-Report Scale (ASRS) 1.1, Depression Anxiety and Stress Scale-21 (DASS-21) and Behaviour and Symptom Identification Scale (BASIS-32).
Results
The sex ratio was lower in the ADHD adulthood versus childhood diagnosed group (1.4:1 versus 4.9:1). Women were likely to be diagnosed 5 years later than men, had lower socioeconomic status, and experienced more ADHD symptoms and trauma.
Conclusion
Women are at risk of delayed diagnosis despite more ADHD symptoms and related problems. There is a need for increased adult ADHD services and health professional education in Australia to identify and support adult ADHD.
Key points
What is already known about this topic:
• (1) Attention deficit hyperactivity disorder (ADHD) persists into adulthood and affects around 2-3% of adults.
• (2) Adult ADHD is associated with high levels of psychiatric comorbidity.
• (3) There is very little research on the presentation of Australian adults with ADHD.
What this topic adds:
• (1) This research describes the clinical presentation of 473 Australian adults with ADHD who were consecutively referred to a private psychiatric clinic.
• (2) Women were likely to be diagnosed with ADHD later than men.
• (3) There were high rates of comorbidities and minimal differences between those diagnosed with ADHD in adult versus childhood.
Methylphenidate is a frequently prescribed drug treatment for Attention-Deficit/Hyperactivity Disorder. However, methylphenidate has a mode of action similar to amphetamine and cocaine, both powerful drugs of abuse. There is lingering concern over the long-term safety of methylphenidate, especially in a pediatric population, where the drug may be used for years. We performed a long-term evaluation of the effects of chronic methylphenidate use on a behavioral measure of motivation in male rhesus monkeys. Animals were orally administered a sweetened methylphenidate solution (2.5 or 12.5 mg/kg, twice a day, Mon-Fri) or vehicle during adolescence and into adulthood. These animals were assessed on a test of motivation (progressive ratio responding), during methylphenidate treatment, and after cessation of use. Moreover, animals were evaluated with quantitative T2 MRI about one year after cessation of use.
During the administration phase of the study animals treated with a clinically relevant dose of methylphenidate generally had a higher rate of responding than the control group, while the high dose group generally had a lower rate of responding. These differences were not statistically significant. In the month after cessation of methylphenidate, responding in both experimental groups dropped compared to their previous level of performance (p = 0.19 2.5 mg/kg, p = 0.06 12.5 mg/kg), and responding in the control animals was unchanged (p = 0.81). While cessation of methylphenidate was associated with an acute reduction in responding, group differences were not observed in the following months. These data suggest that methylphenidate did not have a significant impact on responding, but withdrawal from methylphenidate did cause a temporary change in motivation. No changes in T2 MRI values were detected when measured about one year after cessation of treatment.
These data suggest that long-term methylphenidate use does not have a negative effect on a measure of motivation or brain function / microstructure as measured by quantitative T2 MRI. However, cessation of use might be associated with temporary cognitive changes, specifically alteration in motivation. Importantly, this study modeled use in healthy individuals, and results may differ if the same work was repeated in a model of ADHD.
In this chapter the treatment with stimulant and other medications for ADHD, also in combination with other psychiatric medications, is explained and practical tips for finding the right dosage and timing are offered. Also treatment of the delayed sleep phase with sleep hygiene, melatonin and light therapy in adults with ADHD is described.KeywordsTreatment of ADHD in adultsMedicationEvaluation of medical treatmentEffectSide effectsContra-indicationsPregnancyDrivingAlcohol and drug useMelatonin treatmentLight therapy
Introduction to Psychological Science provides students with an accessible, comprehensive, and engaging overview of the field of scientific psychology. It expertly incorporates a variety of perspectives ranging from neuroscience to cultural perspectives at an introductory level. Ray brings together cutting-edge research from traditional psychological literature to modern, evolving perspectives, and creates a unified approach by focusing on three core themes: Behavior and Experience: an analysis of behavior and experiences observed across a variety of everyday life situations. Neuroscience: an examination of psychological experiences through neuroscience lens ranging from genetic/epigenetic to cortical networks as related to psychology. Evolutionary/Human Origins: an exploration of broader scientific questions by examining psychological processes from the perspective of human and cultural history. Through these themes, the book delves into topics like social processes, psychopathology, stress and health, motivation and emotion, developmental sequences, and cognitive functions such as memory, learning, problem solving, and language. Throughout it helps students to understand the nature of psychological science by addressing common myths and misconceptions in psychology, showing how psychological science can be applied to everyday life and how new Research can be created. Additionally, this student-friendly book is packed with pedagogical features, including "concept checks" to test reader knowledge, "extensions" features which show how to apply knowledge, and a comprehensive glossary. Reflecting the latest APA Guidelines concerning the essential elements of an introductory psychology course, this text is core reading for all undergraduate introductory psychology students.
Attention-deficit and hyperactivity disorder (ADHD) is a widespread neurodevelopmental disorder in children and adolescents, persisting into adulthood in a majority of them. ADHD and substance use disorders (SUDs) commonly co-occur in the clinical adult population. The higher-than-normal prevalence rates of SUDs in people with ADHD indicate increased risk for developing SUD. This narrative review deals with the question of whether or not adults with both disorders should be treated with methylphenidate (MPH), addressing specific issues surrounding this form of treatment. MPH is considered as first-line pharmacotherapy for ADHD. However, because of its stimulant-like reinforcing properties, MPH has a significant addictive potential to which persons with SUDs are especially susceptible. Appropriate treatment is therefore complex. Because of concerns about misuse and diversion of MPH medication, clinicians may be reluctant to use MPH to manage ADHD symptoms in these patients. However, it is essential to diagnose and treat ADHD adequately as appropriate therapy reduces the impairments, as well as the risk of developing comorbid disorders and poor treatment response. MPH should not be deprived of these patients because of the risk for misuse, especially as several strategies can be applied to minimize this risk. To conclude, carefully applied guideline-based diagnostics to clarify the potential presence of ADHD as well as a responsible prescription practice in a well-defined therapeutic setting with reliable monitoring of medication intake and regular consultations are essential conditions for a safe and proficient MPH treatment of ADHD in patients with SUD.
Background:
Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial.
Objectives:
To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults.
Search methods:
In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches.
Selection criteria:
Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants.
Data collection and analysis:
Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI.
Main results:
We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest.
Authors' conclusions:
We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.
Frequentemente nei pazienti affetti da Disturbo da Uso di Sostanze (SUD) vengono riscontrate comorbidità psichiatriche, tra queste il Disturbo da Deficit di Attenzione e Iperattività (ADHD) appare tra le comorbidità meno diagnosticate benché più frequenti in letteratura. Diverse ricerche evidenziano che circa un terzo dei pz con ADHD presentano anche una condizione di Addiction.Nell'affrontare i soggetti affetti da questa comorbidità è importante sottolineare la rilevanza dell'assessment clinico al fine di individuare sintomi che frequentemente si sovrappongono e che rendono più complesso il trattamento. Una valutazione accurata deve inoltre tenere presente l'influenza che alcune sostanze d'abuso può esercitare sulle funzioni cognitive che a loro volta influenza il decorso dell'ADHD con frequente riduzione della compliance terapeutica e ripercussione sugli esiti finali.Il trattamento di questo tipo di comorbidità, che richiede una pluralità di interventi, tra cui anche interventi psicologici e socio-educativi, deve porre particolare attenzione alle terapie farmacologiche erogate e ai rischi connessi al loro misuso.Per la riuscita di qualunque trattamento si deve comunque prevedere l'impostazione di un setting altamente integrato nel quale gli interventi specifici vengano erogati contemporaneamente.
Objective
ADHD treatment has positive effects on behavioral symptoms and psychosocial functioning, but studies that follow children treated for ADHD into adulthood are rare.
Method
This follow-up study assessed symptom severity and functional outcomes of adults ( n = 70) who had received individualized ADHD treatment in the Cologne Adaptive Multimodal Treatment (CAMT) Study at ages 6 to 10 years.
Results
Despite symptomatic improvement, participants reported poorer educational and occupational outcomes than expected (e.g., currently unemployed: 17%). They had also been in contact with the justice system more often than expected (e.g., lifetime convictions: 33%) and were impaired on health-related outcomes (e.g., substance use problems: 15%). Several social outcomes were favorable (e.g., long-term relationship/married: 63%).
Conclusion
Compared to the general population or norm samples, CAMT participants had a higher relative risk ( RR) of functional impairments, demonstrating the need for continued support for a substantial proportion of the young adults.
Pharmacotherapy is a central component in the context of an overall therapeutic concept in the treatment of adults with attention deficit hyperactivity disorder (ADHD). In this concept psychosocial interventions with psychoeducation or specific psychotherapy measures also play an important role. In adults three compounds are currently approved for the pharmacological treatment of ADHD in Germany. The long-acting stimulants retarded methylphenidate preparations and lisdexamfetamine can be prescribed. Alternatively, the adrenergic uptake inhibitor atomoxetine can be used. In several meta-analyses good effectiveness and tolerance of these drugs on ADHD psychopathology has been shown. They also improve ADHD-related disorders of emotional regulation capability and disorganization in everyday life. Importantly, an improvement in everyday functionality and quality of life under medication could also be shown in several studies. In this review the evidence for pharmacotherapy of ADHD and its implementation into treatment of adult patients is presented.
Objective:
This study aimed to compare the effect of continuing and discontinuing medications on quality of life of patients with attention-deficit/hyperactivity disorder (ADHD).
Data sources:
PubMed, Cochrane Library, and Embase databases were searched using generic terms for ADHD, discontinuing, continuing, pharmacotherapy, and randomized controlled trials without date or language restrictions.
Study selection:
Of the 3,672 screened studies, 9 met the predefined inclusion criteria on patients with ADHD; 5 of these 9 studies reporting on 1,463 patients (children and adolescents, n = 894; adults, n = 569) measured quality of life and were included in this meta-analysis. Only randomized, double-blind, placebo-controlled withdrawal trials of ADHD medications were included.
Data extraction:
Data were independently extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. Analyses were based on random-effects models.
Results:
Compared with continuing medications, discontinuing them significantly worsened quality of life score in patients with ADHD (standardized mean difference [SMD] = 0.19; 95% CI, 0.08 to 0.30]). Moreover, discontinuing medications worsened this score in children and adolescents with ADHD (SMD = 0.21; 95% CI, 0.06 to 0.36) but not in adults with ADHD (SMD = 0.02; 95% CI, -0.46 to 0.50).
Conclusions:
Discontinuing medications was associated with a small but statistically significant decrease in quality of life among children and adolescents with ADHD but not in adults with ADHD. Quality of life can be applied in pharmacologic interventions regarding continuing and discontinuing medication because this concept is related to individuals' appraisal of their situation. Quality of life is an important factor for planning individualized ADHD medication treatment.
Background and objectives:
In a multisite, randomized study (CTN-0029), a 3-month course of Osmotic-Release Oral System Methylphenidate (OROS-MPH) improved smoking cessation in a group of patients with higher baseline severity in Attention-Deficit/Hyperactivity Disorder (ADHD). This treatment, however, worsened smoking cessation outcome in the group with lower baseline ADHD severity. We want to examine whether this differential treatment effect persisted after OROS-MPH was discontinued.
Methods:
We conducted a secondary analysis of the 1-month follow-up data from CTN-0029 after the discontinuation of OROS-MPH (N = 134). Nicotine patch was tapered during this month. We tested whether OROS-MPH had an effect on self-reported 7-day abstinence by week, as well as possible treatment by baseline ADHD severity interactions.
Results:
Abstinence diminished overall in time after the end of the treatment. In the high baseline severity group, patients who received OROS-MPH had an advantage in 7-day abstinence at week 15 (40% for OROS-MPH vs 20% for placebo, odds ratio = 2.63, P = .028). In the lower severity group (n = 121), no difference was detected (29% for OROS-MPH vs 32% for placebo, P = 1.00) between the two treatment groups. There was also a significant treatment by baseline ADHD severity interaction (P = .03).
Conclusions and scientific significance:
OROS-MPH promotes abstinence beyond the course of treatment for patients with more severe ADHD, while the paradoxical effects in the lower baseline severity group is not persistent after medication discontinuation. Targeting ADHD in smoking cessation as a comorbidity therefore can have broader impact with more precise patient selection. (Am J Addict).
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in difficulties with sustaining attention in tasks and/or hyperactivity/impulsivity. Prevalence rates vary and difficulties in objectively diagnosing ADHD may lead to overdiagnosis or underdiagnosis. Assessment should include a comprehensive evaluation, including history, physical, psychological evaluation, and questionnaires for ADHD. Stimulant medications are effective for treatment, but their use, side effects, and potential for misuse and abuse are a concern, particularly in athletes. Athletes and physicians also need to be aware of the governing body's drug policy for the sport.
Fallbericht. Die 21-jährige Frau E. stellte sich zur
vollstationären Aufnahme zur weiteren
Diagnostik und Terapieoptimierung
vor, nachdem während eines vorangegangenen externen teilstationären Aufenthalts eine Teilremission einer schweren depressiven Episode erreicht werden
konnte und die Verdachtsdiagnose eines
Aufmerksamkeitsdefzitsyndroms im
Erwachsenenalter gestellt worden war.
Zusätzlich hatte die Patientin im SKIDII den Cut-Of-Wert für eine Persönlichkeitsstörung vom emotional-instabilen
Typ, Borderline-Subtyp, überschritten,
sodass diese diferenzialdiagnostisch komorbid ebenfalls in Betracht gezogen
worden war.
Background: Reported prevalence of ADHD in children varies greatly from country to country. There is a similar disparity between rates of medication prescriptions for ADHD, with significant variation existing between rates in USA and Europe. North American studies report that parents have concerns about starting and continuing ADHD medication in children, though little is known about experiences in other geographies and healthcare systems. These studies may inform supports required, and help understand if these concerns may result in different treatment patterns, in other geographies.
Objective: To explore experiences of parents of children who used ADHD medication in Ireland.
Methods: A qualitative methodology was employed. Data were gathered through in-depth semi-structured interviews with ten parents who had a child with ADHD and had commenced medication. Analysis was performed using a phenomenographic approach.
Results: Four descriptive categories relating to parents’ experiences of decision-making emerged. Symptom severity prior to diagnosis, duration of ADHD symptoms and parental struggle to make an informed risk/benefit decision influenced decision-making. The child’s immediate response to medication was identified as an important factor facilitating persistence and adherence. Over time, parents sought to regain some control over and gain confidence in medication management and decision-making.
Conclusions: The decision to use medication in ADHD is difficult and dynamic for parents in Ireland. It is driven by a sense of urgency and powerlessness, mobilizing feelings of doubt, anxiety and guilt before concluding with a sense of autonomy and increased confidence. Lack of awareness of ADHD and treatments, alongside access to care issues, add to parental anxiety in Ireland. This is in contrast to previous North American studies. Current provisions of support and information at the time of ADHD diagnosis are insufficient. Initial reaction to medication options should be explored by clinicians and support continued over time.
The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks.
Methylphenidate (MPH) is widely prescribed for adults with attention deficit hyperactivity disorder (ADHD), but data on long-term treatment and maintenance of effect are lacking. Osmotic release oral system-methylphenidate (OROS–MPH) was evaluated in a 52-wk open-label study in subjects who had previously completed a short-term placebo-controlled trial and short-term open-label extension. Efficacy was assessed using the investigator- and subject-rated Conners’ Adult ADHD Rating Scales (CAARS:O-SV and CAARS:S-S), and the Clinical Global Impression – Severity (CGI-S), Sheehan Disability Scale (SDS) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Subjects completing ≥52 wk of treatment were eligible for a 4-wk randomized, placebo-controlled withdrawal phase in which loss of treatment effect was assessed using CAARS:O-SV and CGI-S. In the open-label phase (n=156), mean CAARS:O-SV score decreased from baseline by 1.9±7.8 (p<0.01), and small, statistically significant improvements from baseline were observed for CAARS:S-S, CGI-S and SDS. In the double-blind phase (OROS-MPH, n=23; placebo, n=22), CAARS:O-SV increased from double-blind baseline in the OROS-MPH and placebo arms (4.0±7.6 vs. 6.5±7.8, not statistically significant). Long-term OROS-MPH treatment was well tolerated, and there was no evidence of withdrawal or rebound after discontinuation. In conclusion, the short-term benefits of OROS-MPH continue during long-term open-label treatment. Maintenance of efficacy in a placebo-controlled withdrawal design remains to be confirmed in larger patient populations.
There is increased global recognition of attention deficit hyperactivity disorder (ADHD) as a serious medical condition with long-term consequences. Although originally conceived of as a childhood disorder, ADHD is being increasingly recognized in adults. Individual geographic regions may have specific interests and objectives for the study of ADHD. A systematic review of long-term outcomes (LTOs) in ADHD was conducted to evaluate research on ADHD LTOs on a global scale. Studies that were at least two years in duration were examined. We identified nine outcomes of interest and classified studies by specific geographical regions, age groups studied and study design by region and over time. Published studies of LTOs in ADHD have increased in all geographical regions over the past three decades, with a peak number of publications in 2008. Although many world regions have published on ADHD LTOs, the majority of studies have emerged from the US and Canada, followed by Europe. While investigators in the US and Canada were predominantly interested in drug addiction as a LTO, European researchers were more interested in antisocial behavior, and Eastern Asian investigators focused on both of these LTOs as well as self-esteem. Proportionally fewer prospective longitudinal studies and proportionally more retrospective and cross-sectional studies have been published in more recent decades. Finally, more studies focusing on ADHD in adolescents and adults have been conducted in recent years, and particularly adolescents in Eastern Asia. This systematic review analysis of publication trends in ADHD LTOs reflects geographically-based interests that change over time.
More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety.
To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults.
Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers).
Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias.
During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years.
Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.
Attention-deficit hyperactivity disorder (ADHD) is highly prevalent in prison inmates, but pharmacological treatment has not yet been evaluated in this group.
To evaluate osmotic-release oral system (OROS) methylphenidate in adult male long-term prison inmates with ADHD.
Randomised, double-blind, placebo-controlled 5-week trial, followed by 47-week open-label extension in 30 prison inmates with ADHD and comorbid disorders. Primary outcome was level of ADHD symptoms after 5 weeks, evaluated by a masked assessor. Secondary outcomes were self-reported ADHD symptoms, global severity and global functioning throughout the 52-week trial, and post hoc treatment response and numbers needed to treat (NNT) (trial registration: NCT00482313.)
Treatment significantly improved ADHD during the trial (P<0.001; Cohen's d = 2.17), with reduced symptom severity and improved global functioning. The placebo response, cardiovascular measures and adverse events were non-significant; the NNT was 1.1. Attention-deficit hyperactivity disorder symptoms, global severity and global functioning continued to improve during the open-label extension.
Osmotic-release oral system methylphenidate is an effective treatment for adult male prison inmates with ADHD.
Adverse-event reports from North America have raised concern that the use of drugs for attention deficit-hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events.
We conducted a retrospective cohort study with automated data from four health plans (Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology), with 1,200,438 children and young adults between the ages of 2 and 24 years and 2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs. We identified serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) from health-plan data and vital records, with end points validated by medical-record review. We estimated the relative risk of end points among current users, as compared with nonusers, with hazard ratios from Cox regression models.
Cohort members had 81 serious cardiovascular events (3.1 per 100,000 person-years). Current users of ADHD drugs were not at increased risk for serious cardiovascular events (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.31 to 1.85). Risk was not increased for any of the individual end points, or for current users as compared with former users (adjusted hazard ratio, 0.70; 95% CI, 0.29 to 1.72). Alternative analyses addressing several study assumptions also showed no significant association between the use of an ADHD drug and the risk of a study end point.
This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low. (Funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration.).
During the last few years several clinical guidelines on attention-deficit hyperactivity disorder (ADHD) have been published by national and international medical societies. To systematically review and compare recommendations of selected ADHD guidelines, we performed a systematic search in online guideline databases and PubMed in order to retrieve guideline texts. Guidelines meeting inclusion criteria were reviewed and recommendations on assessment and treatment extracted. The AGREE instrument was used to assess methodological quality. Of the 26 guidelines identified, 13 were selected for further analysis: 11 guidelines deal with ADHD in childhood and adolescence and 5 guidelines cover transitional patients and/or ADHD in adults. The methodological quality of ADHD guidelines is moderate to good. They reflect similarities and differences of healthcare systems. Diagnosis throughout the lifespan is based on a detailed clinical history. There is greater agreement on evidence-based pharmacological treatment than on psychosocial interventions, reflecting the strength of evidence.
Data on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated.
After a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale - Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions - Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis.
A total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes.
Improvements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.
Objective:
ADHD is associated with poor functional outcomes. The objectives were to investigate the prevalence of functional impairment and occupational status in a clinically referred sample of adults with ADHD and explore factors predicting occupational outcome.
Method:
A sample of 149 adults with a confirmed diagnosis of ADHD participated in the present study. Cross-sectional data were collected from the participant's medical records and from self-report questionnaires. A multiple regression model was applied to identify possible predictors of occupational outcome.
Results:
Only 22.2% had ordinary work as their source of income, compared with 72% in the general population. The most prevalent comorbid disorders were lifetime depression (37.8%), substance abuse (28.1%), and alcohol abuse (23.3%). Age at first treatment with central stimulants and inattentiveness negatively predicted occupational outcome.
Conclusion:
Adult ADHD was associated with lower educational attainment and lower level of employment. Later age of first central stimulant treatment and higher inattentiveness ratings were associated with lower level of employment.
The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks.
Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe.
The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated.
Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated?
ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group.
This open-label trial followed a previously reported randomized, placebo-controlled trial of osmotic release oral system (OROS) methylphenidate (MPH) for the treatment of personality disorder (PD). Important findings from the double-blind phase are reexamined for long-term significance.
Of 41 patients who completed the double-blind, placebo-controlled trial, 34 continued into this open-label phase. The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) measured outcome. Patients were categorized using previously defined attention-deficit/hyperactivity disorder (ADHD) groups: ADHD alone, ADHD with emotional dysregulation (ADHD + ED), and ADHD plus emotional dysregulation plus oppositional symptoms (ADHD + ED + ODD); and 3 post hoc personality categories: patients with no PD (PD-negative), patients with 1 PD (PD-positive), and patients meeting criteria for 2 or more PDs (PD-plus).
Three WRAADDS-defined ADHD dimensions improved at similar levels (attention + disorganization, 61%; hyperactivity + impulsivity, 60%; and emotional dysregulation, 66%). All ADHD subgroups (ADHD alone, ADHD + ED, and ADHD + ED + ODD) improved. ADHD + ED + ODD patients had the highest level of social maladjustment at baseline and showed the most long-term improvement in this area. PD-plus patients were less likely to complete the study or show improvement. Sixty-five percent of treatment responders were on moderate doses (< or =54 mg/d) of OROS MPH. Vital signs and ECGs did not differ from baseline.
Eighteen (44%) patients completed the trial. All 3 ADHD dimensions showed similar, well-maintained improvement. Patients with several PDs responded poorly to treatment in this small trial.
The Quality of Life, Effectiveness, Safety, and Tolerability (QU.E.S.T.) study was designed to evaluate effectiveness of long-acting amphetamines in adults with attention-deficit/hyperactivity disorder (ADHD) in community practice settings. This article reports moderators and mediators of symptoms and quality of life outcomes.
This was an open-label study of 725 adults with DSM-IV-diagnosed ADHD, treated with mixed amphetamine salts extended release and followed for up to 8 months. Multiple regressions were used to determine if patient moderators impact response in ADHD symptoms and how ADHD symptoms and medication satisfaction mediate quality of life. The study was conducted from December 2003 to December 2004.
Amphetamine treatment of ADHD resulted in a robust and enduring symptom response. Patient characteristics such as age, female gender, severity of illness, and treatment-naive status moderate improved symptom outcome. Symptom change and satisfaction with medication independently mediate change in mental but not physical quality of life outcomes. There is no time lag between changes in symptoms and improved quality of life. Attention is a stronger mediator of ADHD-specific quality of life outcomes than disruptive behavior.
If symptoms and quality of life improve simultaneously, improvement in quality of life can be understood as more than just a downstream, secondary effect of symptom remission. Satisfaction with medication is a direct measure of the complex interplay of symptom change, tolerability, and patient perception of treatment that predicts self-report of quality of life benefits. Although the disruptive symptoms of ADHD are more obvious, adults self-report that attention has greater impact.
Diagnosing attention deficit/hyperactivity disorder (ADHD) in patients with substance use disorder (SUD) is a complicated process in which a screening tool may be useful. We analyzed the ASRS-v1.1 validity in patients with SUD, considering the addiction severity and co-morbidity with depressive disorders, antisocial and borderline personality.
Eighty outpatients with SUD were evaluated with the following instruments: ASRS-v1.1, CAAD-II, EuropASI, SCID-I, SCID-II. A factor analysis was performed with Varimax rotation to determine the structure of the intercorrelations among the items. Accuracy of ASRS-v1.1 was also analyzed.
The diagnostic interview CAADID used as a gold standard indicated that 20% (95% confidence interval [CI]: 11-29) meet the criteria for ADHD. The ASRSv1.1 factor structure is marked by two factors related to inattention and hyperactivity / impulsivity that account for 67.7% of the variance. ASRS-v1.1, with a 4 cut-off, showed an 87.5% sensitivity and 68.6% specificity.
ASRS-v1.1 is a simple screening tool that is useful and has acceptable validity for the identification of ADHD among addicted patients.
To determine the effects of symptom profile, comorbid psychiatric problems, and treatment on occupational outcome in adult ADHD patients.
Adult ADHD patients (N = 414) responded to questionnaires rating past and present symptoms of ADHD, comorbid conditions, treatment history, and work status.
Of the patients, 24% reported being in work, compared to 79% in a population-based control group (N = 359). Combined subtype of ADHD, substance abuse, and a reported history of depression or anxiety were correlated with being out of work. Current and past medical treatment of ADHD was correlated with being in work. Logistic regression analyses showed that stimulant therapy during childhood was the strongest predictor for being in work as adults (odds ratio = 3.2, p = .014).
Early recognition and treatment of ADHD is a strong predictor of being in work as an adult, independently of comorbidity, substance abuse, and current treatment.
Introduction
Attention-deficit/hyperactivity disorder (ADHD) affects many adults who had ADHD in childhood. Although stimulants and methylphenidate in particular are a common off-label treatment for adult patients with ADHD in European countries, little is known about their long-term efficacy and safety.
Methods
A randomized, 24-week double-blind, placebo-controlled, parallel-design study of extended-release methylphenidate (MPH ER) in 359 adult individuals with ADHD according to DSM-IV. Standardized instruments were used for diagnosis. Treatment was started with MPH ER doses of 10 mg/day and titrated up to 60 mg/day, depending on individual efficacy and tolerability. Mean daily MPH SR dose was 0.55 mg/kg.
Results
Treatment with MPH ER resulted in clinical and statistically significant reductions of ADHD symptoms rated with the Wender-Reimherr adult attention deficit disorder scale (WRAADDS) and symptoms of inattention and hyperactivity/impulsivity according to DSM-IV, respectively. Improvements were maintained significant versus placebo up to week 24 of treatment. At endpoint, 61% of the subjects receiving MPH ER were rated as responders according to the a priori definition of response of more than 30% reduction of the WRAADDS score, compared to 42% in the placebo group. The second defined response criterion of much or very much improved on the clinical global impression scale (CGI) was fulfilled by 55% of subjects receiving MPH ER and 37% of subjects receiving placebo. MPH ER treatment was associated with a statistically significant increase of pulse at week 4 (72 bpm at baseline, 77 bpm at week 4). There were no significant differences of heart rate or blood pressure between treatment and placebo groups at any time point.
Discussion
MPH ER treatment in low to moderate doses was effective and safe in the treatment of ADHD in adults. Efficacy measures were clinical and statistically significant and robustly sustained during the 24-week observation period. In this study, no clinical significant effects on blood pressure but a transient increase of the heart rate were found. The interpretation of the results is limited by the low dose-range used in this study, the high drop-out rate and placebo-response which might have affected the therapeutic effect size.
Over 30% of children with ADHD treated with a rigorous multimodal intervention in the MTA study did not reach full functional remission. New long-acting drugs have been developed with this treatment goal in mind.
Presentations at the 2004 Annual Meeting of the Canadian Academy of Child and Adolescent Psychiatry discussed the development of long-acting drugs for ADHD and clinical studies of their efficacy; these presentations are summarized below.
Concerta(R) OROS-MPH releases methylphenidate (MPH) in an initial bolus, followed by increasing concentrations throughout the day. This pattern of drug delivery overcomes the development of acute tolerance; classroom analog studies have shown that ADHD symptoms and academic productivity are thereby maintained for 12 hours. A larger open-label study showed that efficacy was maintained through the 12-month study period. An 8-week open-label trial found that OROS-MPH produced significantly higher remission rates than immediate-release MPH (44% vs 16%; p = 0.0002), as well as significantly higher Clinical Global Impression and parent satisfaction scores. Adderall XR(R), an extended-release formulation of mixed amphetamine salts, has recently been withdrawn from the market.
Long-acting stimulant formulations have dramatically changed the landscape of ADHD practice.
Treatment with psychostimulant medication has been shown to improve scholastic functioning in children with attention-deficit/hyperactivity disorder (ADHD). However, the extent to which long-term academic gains are apparent in those having received such treatment remains elusive. This study examined prospectively the relationship of childhood stimulant treatment to academic functioning during adolescence. Children (n = 169) were initially recruited and diagnosed with ADHD when they were 7-11 years old. A subsample of those with childhood ADHD (n = 90) was reevaluated on average 9.13 (SD = 1.5) years later. Probands who did and did not receive treatment with stimulant medication were compared to each other and to a never-ADHD comparison group (n = 80) on three subtests from the Wechsler Individual Achievement Test-II (WIAT-II), as well as high school grade point average (GPA) and number of retentions in school as derived from school records. Analyses of covariance controlling for severity of childhood ADHD symptoms indicated that probands treated with psychostimulant medication achieved better academic outcomes, as measured by WIAT-II subtests and high school GPA, than those not treated with psychostimulants (p < .05). However, treated probands did not fare as well as the never-ADHD comparison group. Psychostimulant treatment for children with ADHD may benefit long-term adolescent academic performance, although the extent of improvement is likely to vary as a function of multiple factors.
Objective:
Despite growing interest in adult attention deficit hyperactivity disorder (ADHD), little is known about its prevalence or correlates.
Method:
A screen for adult ADHD was included in a probability subsample (N=3,199) of 18-44-year-old respondents in the National Comorbidity Survey Replication, a nationally representative household survey that used a lay-administered diagnostic interview to assess a wide range of DSM-IV disorders. Blinded clinical follow-up interviews of adult ADHD were carried out with 154 respondents, oversampling those with positive screen results. Multiple imputation was used to estimate prevalence and correlates of clinician-assessed adult ADHD.
Results:
The estimated prevalence of current adult ADHD was 4.4%. Significant correlates included being male, previously married, unemployed, and non-Hispanic white. Adult ADHD was highly comorbid with many other DSM-IV disorders assessed in the survey and was associated with substantial role impairment. The majority of cases were untreated, although many individuals had obtained treatment for other comorbid mental and substance-related disorders.
Conclusions:
Efforts are needed to increase the detection and treatment of adult ADHD. Research is needed to determine whether effective treatment would reduce the onset, persistence, and severity of disorders that co-occur with adult ADHD.
Psychostimulant drugs have for decades been considered the cornerstone of ADHD treatment. Non-stimulant drugs have also been reported successful. However, many controlled studies exclude patients with comorbidities typical for patients seen in clinical setting. Many patients are also considered non-responders to medication. Current knowledge might not be directly useful to clinicians. The present article reviews the literature on pharmacological and psychotherapeutic treatment in adult ADHD emphasizing comorbidity and other clinically important factors, as well as ADHD specific outcomes. Thirty-three relevant studies of pharmacotherapy and three studies of psychotherapy were included. Most subjects had little current comorbidity, but some studies included subjects with substance use disorder. Significant effect of treatment on ADHD symptoms was found in most studies using pharmacotherapy and all studies of psychotherapy. Both positive and negative effects on comorbid anxiety and depression measures were reported. Pharmacotherapy did not seem to have effect on substance use disorder. Few pharmacotherapy studies conducted any long-term follow-up; two studies that did, found that most subjects had discontinued medication. A clear-cut dose-respons relationship was not substanciated. In conclusion, clinicians have good support for both pharmacological and psychotherapeutic treatment of ADHD in adults, but should take additional measures to deal with comorbidities as well as treatment adherence.
Introduction:
Attention-deficit/hyperactivity disorder (ADHD) affects many adults who had ADHD in childhood. Although stimulants and methylphenidate in particular are a common off-label treatment for adult patients with ADHD in European countries, little is known about their long-term efficacy and safety.
Methods:
A randomized, 24-week double-blind, placebo-controlled, parallel-design study of extended-release methylphenidate (MPH ER) in 359 adult individuals with ADHD according to DSM-IV. Standardized instruments were used for diagnosis. Treatment was started with MPH ER doses of 10 mg/day and titrated up to 60 mg/day, depending on individual efficacy and tolerability. Mean daily MPH SR dose was 0.55 mg/kg.
Results:
Treatment with MPH ER resulted in clinical and statistically significant reductions of ADHD symptoms rated with the Wender-Reimherr adult attention deficit disorder scale (WRAADDS) and symptoms of inattention and hyperactivity/impulsivity according to DSM-IV, respectively. Improvements were maintained significant versus placebo up to week 24 of treatment. At endpoint, 61% of the subjects receiving MPH ER were rated as responders according to the a priori definition of response of more than 30% reduction of the WRAADDS score, compared to 42% in the placebo group. The second defined response criterion of much or very much improved on the clinical global impression scale (CGI) was fulfilled by 55% of subjects receiving MPH ER and 37% of subjects receiving placebo. MPH ER treatment was associated with a statistically significant increase of pulse at week 4 (72 bpm at baseline, 77 bpm at week 4). There were no significant differences of heart rate or blood pressure between treatment and placebo groups at any time point.
Discussion:
MPH ER treatment in low to moderate doses was effective and safe in the treatment of ADHD in adults. Efficacy measures were clinical and statistically significant and robustly sustained during the 24-week observation period. In this study, no clinical significant effects on blood pressure but a transient increase of the heart rate were found. The interpretation of the results is limited by the low dose-range used in this study, the high drop-out rate and placebo-response which might have affected the therapeutic effect size.
The realization that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood has led to increased frequency of diagnosis and treatment in adults. Osmotic release oral system (OROS) methylpheni-date is a long-acting stimulant demonstrated to be effective in the treatment of children and adolescents with ADHD.
Forty-seven adults entered and 41 completed this double-blind, placebo-controlled, crossover trial of OROS methylphenidate. Each double-blind arm lasted 4 weeks; data were collected from August 2004 through December 2005. Subjects met both DSM-IV-TR and Utah Criteria for ADHD in adults. Outcome measures included the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), the adult ADHD-Rating Scale (ADHD-RS), and the Clinical Global Impressions-Improvement scale (CGI-I). At baseline, subjects were categorized as having significant emotional symptoms with the WRAADDS and/or significant oppositional-defiant symptoms using a self-report scale assessing the DSM-IV criteria for oppositional defiant disorder.
17% of the sample (N = 8) had ADHD alone, 38% (N = 18) had ADHD plus significant emotional symptoms, and 40% (N = 19) had ADHD with both significant emotional and oppositional symptoms. At a mean +/- SD dose of 64.0 +/- 23.3 (0.75 mg/kg), OROS methylphenidate proved superior to placebo for all clinical measures: total WRAADDS score decrease of 42% versus 13%, respectively, p < .001 and total ADHD-RS score decrease of 41% versus 14%, respectively, p = .003, plus the subscales addressing inattention, hyperactivity/ impulsivity, and emotional dysregulation.
OROS methylphenidate proved effective in treating adult ADHD. ADHD alone was relatively uncommon. Over 80% of our patients had ADHD with a combination of emotional and/or oppositional symptoms.
Prospective young adult outcomes (mean age 21.8 years) of children who had been diagnosed as having attention deficit disorder with hyperactivity and who had been treated with methylphenidate for at least 3 years were compared with those of a matched normal control group and a group of hyperactive young adults who had not received any stimulant treatment. Results suggest that in many areas, e.g., school, work, and personality disorders, stimulant-treated hyperactives function significantly worse than matched normal controls but similar to untreated hyperactives. In some areas, e.g., less car accidents, more positive view of childhood, later delinquency, and better social skills and self-esteem, stimulant-treated hyperactives did better than their untreated counterparts. Thus stimulant treatment for hyperactive children may not eliminate educational work or life difficulties, but may result in less social ostracism and improved feelings toward themselves and others.
The authors sought to determine whether use of methylphenidate in adults is associated with elevated rates of serious cardiovascular events compared with rates in nonusers.
This was a cohort study of new users of methylphenidate based on administrative data from a five-state Medicaid database and a 14-state commercial insurance database. All new methylphenidate users with at least 180 days of prior enrollment were identified. Users were matched on data source, state, sex, and age to as many as four comparison subjects who did not use methylphenidate, amphetamines, or atomoxetine. A total of 43,999 new methylphenidate users were identified and matched to 175,955 nonusers. Events of primary interest were 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, and 4) a composite endpoint of stroke or myocardial infarction.
The age-standardized incidence rate per 1,000 person-years of sudden death or ventricular arrhythmia was 2.17 (95% CI=1.63-2.83) in methylphenidate users and 0.98 (95% CI=0.89-1.08) in nonusers, for an adjusted hazard ratio of 1.84 (95% CI=1.33-2.55). Dosage was inversely associated with risk. Adjusted hazard ratios for stroke, myocardial infarction, and the composite endpoint of stroke or myocardial infarction did not differ statistically from 1.
Although initiation of methylphenidate was associated with a 1.8-fold increase in risk of sudden death or ventricular arrhythmia, the lack of a dose-response relationship suggests that this association may not be a causal one.
To examine the literature pertaining to the diversion and misuse of pharmaceutical stimulants.
Relevant literature was identified through comprehensive MEDLINE, EMBASE and PubMed searches.
The evidence to date suggests that the prevalence of diversion and misuse of pharmaceutical stimulants varies across adolescent and young adult student populations, but is higher than that among the general population, with the highest prevalence found among adults with attention deficit-hyperactive disorder (ADHD) and users of other illicit drugs. Concerns that these practices have become more prevalent as a result of increased prescribing are not supported by large-scale population surveys. Information on trends in misuse in countries where there have been recent increases in prescription and consumption rates, however, is limited. Little is known about the frequency and chronicity of misuse, or the extent of associated harms, particularly among those populations, i.e. adolescents, young adult student populations, those with ADHD and illicit drug users, where abuse may be more likely to occur.
Continued monitoring of the diversion and misuse of pharmaceutical stimulants is of major clinical importance. Despite recognition of the abuse liability of these medications, there is a paucity of data on the prevalence, patterns and harms of diversion and misuse among populations where problematic use and abuse may be most likely to occur (e.g. adolescents, young adults, illicit drug users). Comprehensive investigations of diversion and misuse among these populations should be a major research priority, as should the assessment of abuse and dependence criteria among those identified as regular users.
Questions about the long-term effects of psychostimulant medication are frequently raised in the public domain. There is a need to articulate the methodological challenges to addressing this question, both to assist in the interpretation of existing research and to inform future research.
Two peer-reviewed studies and one published report have attempted to address the issue of long-term effects of psychostimulant medication. One is favourable, one found no benefit, and the third showed harm. All three studies struggled to deal with methodological challenges such as the variable time course of the disorder, variability in persistence and adherence with treatment, and self-selection for treatment continuation.
Future research examining the long-term effects of psychostimulant treatment will of necessity be naturalistic, but must be able to control for treatment quality, treatment adherence, and natural variation in the course of attention-deficit/hyperactivity disorder. It would be helpful to distinguish between long-term effects of treatment and effects of long-term treatment.
A three-year open-label study of atomoxetine in adults with ADHD followed two multicenter, double-blind trials. In the double-blind trials, female gender and higher levels of emotional symptoms were associated with better outcome. Following a 4-week placebo washout period, 384 (of 536) subjects continued into the open-label study. 61% of subjects entering this open-label study remained after 6 months at an average dose of 100 mg/day. Subjects who had previously responded to double-blind atomoxetine achieved maximum response after 8 weeks of open-label medication, but others continued to improve for 36 weeks. Women improved more (7.7 ± 6.4) than men (6.1 ± 6.4) on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) (P = .007) and the Conners' Adult ADHD Rating Scale (P = .03). Subjects with emotional dysregulation improved more than others on the WRAADDS (P = .001). Responders ultimately improved approximately 60% in attentional, hyperactive/impulsive, and emotional symptoms. Thirty-nine percent of atomoxetine double-blind non-responders became responders during open-label treatment.
To examine the impact of baseline severity on lisdexamfetamine dimesylate (LDX) efficacy in a long-term study of adults with attention-deficit/hyperactivity disorder (ADHD).
Adults from a 4-week, placebo-controlled, forced dose-escalation study with LDX (30-70 mg/day) or placebo were enrolled in a long-term, open-label dose-optimization study for an additional 12 months. In post hoc analyses, participants were stratified by baseline severity (from the prior short-term study) with Clinical Global Impressions-Severity (CGI-S) scores of 4 (moderately), 5 (markedly), or ≥6 (severely/extremely ill). ADHD-Rating Scale IV (ADHD-RS-IV) with adult prompts (primary) and CGI-Improvement (CGI-I) were used to assess effectiveness. Clinical response was defined as a ≥30% decrease in ADHD-RS-IV from baseline and a CGI-I of 1 or 2; symptomatic remission was defined as ADHD-RS-IV ≤18. Treatment-emergent adverse events (TEAEs) were monitored.
Participants had baseline CGI-S scores of 4 (n = 114), 5 (n = 188), or ≥6 (n = 43). At endpoint, mean (SD) change from baseline in ADHD-RS-IV was greater (p < 0.0001) for participants with CGI-S = 5 (-26.4 [11.77]) and ≥6 (-32.3 [9.81]) than for participants with CGI-S = 4 (-19.5 [9.97]). At endpoint, 81.6%, 84.6%, and 88.4% of participants were very much/much improved (CGI-I of 1 or 2) in CGI-S categories of 4, 5, and ≥6, respectively. Clinical response criteria were met by 78.9%, 83.5%, and 88.4% and symptomatic remission criteria by 64.0%, 65.4%, and 72.1% of participants with CGI-S = 4, 5, and ≥6, respectively. The most frequently reported TEAEs with participant incidence ≥10% for any LDX dose were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%).
Some aspects of these analyses (e.g., open-label design without placebo control, inclusion and exclusion criteria of the demographic profile of participants, and the post hoc nature of the statistical analysis) limit interpretation. However, long-term LDX treatment demonstrated increased degree of symptom improvement with greater baseline symptom severity. Rates of clinical response and symptomatic remission tended to be greater for those with greater baseline severity. LDX demonstrated a safety profile consistent with long-acting stimulant use.