Reviewing the role of emerging therapies in the ADHD armamentarium.
TL;DR: A robust pipeline of stimulants and nonstimulants in development are found, formulated to optimize onset and duration of effect, alter the time of administration, obviate the need to swallow whole capsules or tablets and to deter abuse.
Abstract: Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder that can be treated with both pharmacologic and nonpharmacologic modalities. Effective drug treatm...
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01 Jan 2017
TL;DR: In this article, the authors conducted a systematic review and meta-analysis of OST in children with ADHD and found that OST leads to moderate improvements in organizational skills as rated by teachers and large improvements by parents, while more modest improvements were observed on the ratings of symptoms of inattention and academic performance.
Abstract: BACKGROUND
In addition to problems with attention and hyperactivity, children with ADHD present with poor organizational skills required for managing time and materials in academic projects. Organizational skills training (OST) has been increasingly used to address these deficits. We conducted a systematic review and meta-analysis of OST in children with ADHD.
OBJECTIVES
The objective of this study was to systematically review the evidence of the effects of OST for children with ADHD for organizational skills, attention, and academic performance.
METHODS
We searched 3 electronic databases to locate randomized controlled trials published in English in peer-reviewed journals comparing OST with parent education, treatment-as-usual, or waitlist control conditions. Standardized mean difference effect sizes from the studies were statistically combined using a random-effects meta-analyses across six outcomes: teacher- and parent-rated organizational skills, teacher- and parent-rated inattention, teacher-rated academic performance, and Grade Point Average (GPA). Risk of bias was assessed for randomization, allocation concealment, blinding of participants and treatment personnel, blinding of outcome assessors, incomplete outcome data, and selective outcome reporting.
RESULTS
Twelve studies involving 1054 children (576 treatment, 478 control) were included in the meta-analyses. Weighted mean effect sizes for teacher- and parent-rated outcome measures of organizational skills were g=0.54 (95% CI 0.17 to 0.91) and g=0.83 (95% CI 0.32 to 1.34), respectively. Weighted mean effect sizes of teacher- and parent-rated symptoms of inattention were g=0.26 (95% CI 0.01 to 0.52) and g=0.56 (95% CI 0.38 to 0.74), respectively. Weighted standardized mean effect size for teacher-rated academic performance and GPA were g=0.33 (95% CI 0.14 to 0.51) and g=0.29 (95% CI 0.07 to 0.51), respectively.
CONCLUSIONS
OST leads to moderate improvements in organizational skills of children with ADHD as rated by teachers and large improvements as rated by parents. More modest improvements were observed on the ratings of symptoms of inattention and academic performance.
PROTOCOL REGISTRATION
PROSPERO (CRD42015019261).
19 citations
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TL;DR: A review of FDA approved and emerging medication options while providing guidelines for pharmacologic management of adult ADHD is presented in this paper . But, limitations still persist in available psychotropics for certain patient populations such as those with comorbid substance use or cardiovascular illness.
4 citations
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TL;DR: In this study, SPN-812 at 100 mg and 200 mg doses met the primary and secondary objectives with statistical significance and was well tolerated in children ages 6-11yrs with ADHD.
Abstract: Study Objective:
SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P301) evaluated the efficacy and safety of once-daily SPN-812 at doses of 100 and 200 mg compared to placebo in children ages 6-11yrs with ADHD. Method:
Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, a Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=477) were randomized 1:1:1 to placebo:100 mg SPN-812:200 mg SPN-812. The 6-week treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=460; placebo=155, 100 mg=147, 200 mg=158). The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and in Weiss Functional Impairment Rating Scale-Parent Version (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale. Results:
Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 100 mg and 200 mg SPN-812 treatment groups beginning at week 1 (p=0.0004, p=0.0244; respectively) through EOS (p=0.0004, p<0.0001; respectively). Significant improvement at EOS for both 100 mg and 200 mg SPN-812 compared to placebo was also observed in CGI-I score (p=0.0020, p<0.0001; respectively), Connors 3-PS Composite T-score (p=0.0003, p=0.0002; respectively), and in WFIRS-P total average score (p=0.0019, p=0.0002, respectively). The most common (≥5%) treatment-related AEs reported were somnolence, decreased appetite, and headache. Conclusions:
In this study, SPN-812 at 100 mg and 200 mg doses met the primary and secondary objectives with statistical significance. AE-related dropouts were ≤5%, indicating SPN-812 treatment was well tolerated.
This study is an encore of a poster presentation at the 2019 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP). Funding Acknowledgements:
This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.
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TL;DR: An issue concerning the criteria for tic disorders is highlighted, and how this might affect classification of dyskinesias in psychotic spectrum disorders.
Abstract: Given the recent attention to movement abnormalities in psychosis spectrum disorders (e.g., prodromal/high-risk syndromes, schizophrenia) (Mittal et al., 2008; Pappa and Dazzan, 2009), and an ongoing discussion pertaining to revisions of the Diagnostic and Statistical Manuel of Mental Disorders (DSM) for the upcoming 5th edition, we would like to take this opportunity to highlight an issue concerning the criteria for tic disorders, and how this might affect classification of dyskinesias in psychotic spectrum disorders.
Rapid, non-rhythmic, abnormal movements can appear in psychosis spectrum disorders, as well as in a host of commonly co-occurring conditions, including Tourette’s Syndrome and Transient Tic Disorder (Kerbeshian et al., 2009). Confusion can arise when it becomes necessary to determine whether an observed movement (e.g., a sudden head jerk) represents a spontaneous dyskinesia (i.e., spontaneous transient chorea, athetosis, dystonia, ballismus involving muscle groups of the arms, legs, trunk, face, and/or neck) or a tic (i.e., stereotypic or patterned movements defined by the relationship to voluntary movement, acute and chronic time course, and sensory urges). Indeed, dyskinetic movements such as dystonia (i.e., sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures or positions) closely resemble tics in a patterned appearance, and may only be visually discernable by attending to timing differences (Gilbert, 2006).
When turning to the current DSM-IV TR for clarification, the description reads: “Tic Disorders must be distinguished from other types of abnormal movements that may accompany general medical conditions (e.g., Huntington’s disease, stroke, Lesch-Nyhan syndrome, Wilson’s disease, Sydenham’s chorea, multiple sclerosis, postviral encephalitis, head injury) and from abnormal movements that are due to the direct effects of a substance (e.g., a neuroleptic medication)”. However, as it is written, it is unclear if psychosis falls under one such exclusionary medical disorder. The “direct effects of a substance” criteria, referencing neuroleptic medications, further contributes to the uncertainty around this issue. As a result, ruling-out or differentiating tics in psychosis spectrum disorders is at best, a murky endeavor.
Historically, the advent of antipsychotic medication in the 1950s has contributed to the confusion about movement signs in psychiatric populations. Because neuroleptic medications produce characteristic movement disorder in some patients (i.e. extrapyramidal side effects), drug-induced movement disturbances have been the focus of research attention in psychotic disorders. However, accumulating data have documented that spontaneous dyskinesias, including choreoathetodic movements, can occur in medication naive adults with schizophrenia spectrum disorders (Pappa and Dazzan, 2009), as well as healthy first-degree relatives of chronically ill schizophrenia patients (McCreadie et al., 2003). Taken together, this suggests that movement abnormalities may reflect pathogenic processes underlying some psychotic disorders (Mittal et al., 2008; Pappa and Dazzan, 2009).
More specifically, because spontaneous hyperkinetic movements are believed to reflect abnormal striatal dopamine activity (DeLong and Wichmann, 2007), and dysfunction in this same circuit is also proposed to contribute to psychosis, it is possible that spontaneous dyskinesias serve as an outward manifestation of circuit dysfunction underlying some schizophrenia-spectrum symptoms (Walker, 1994). Further, because these movements precede the clinical onset of psychotic symptoms, sometimes occurring in early childhood (Walker, 1994), and may steadily increase during adolescence among populations at high-risk for schizophrenia (Mittal et al., 2008), observable dyskinesias could reflect a susceptibility that later interacts with environmental and neurodevelopmental factors, in the genesis of psychosis.
In adolescents who meet criteria for a prodromal syndrome (i.e., the period preceding formal onset of psychotic disorders characterized by subtle attenuated positive symptoms coupled with a decline in functioning), there is sometimes a history of childhood conditions which are also characterized by suppressible tics or tic like movements (Niendam et al., 2009). On the other hand, differentiating between tics and dyskinesias has also complicated research on childhood disorders such as Tourette syndrome (Kompoliti and Goetz, 1998; Gilbert, 2006).
We propose consideration of more explicit and operationalized criteria for differentiating tics and dyskinesias, based on empirically derived understanding of neural mechanisms. Further, revisions of the DSM should allow for the possibility that movement abnormalities might reflect neuropathologic processes underlying the etiology of psychosis for a subgroup of patients. Psychotic disorders might also be included among the medical disorders that are considered a rule-out for tics.
Related to this, the reliability of movement assessment needs to be improved, and this may require more training for mental health professionals in movement symptoms. Although standardized assessment of movement and neurological abnormalities is common in research settings, it has been proposed that an examination of neuromotor signs should figure in the assessment of any patient, and be as much a part of the patient assessment as the mental state examination (Picchioni and Dazzan, 2009).
To this end it is important for researchers and clinicians to be aware of differentiating characteristics for these two classes of abnormal movement. For example, tics tend to be more complex than myoclonic twitches, and less flowing than choreoathetodic movements (Kompoliti and Goetz, 1998). Patients with tics often describe a sensory premonition or urge to perform a tic, and the ability to postpone tics at the cost of rising inner tension (Gilbert, 2006). For example, one study showed that patients with tic disorders could accurately distinguish tics from other movement abnormalities based on the subjective experience of some voluntary control of tics (Lang, 1991). Another differentiating factor derives from the relationship of the movement in question to other voluntary movements. Tics in one body area rarely occur during purposeful and voluntary movements in that same body area whereas dyskinesia are often exacerbated by voluntary movement (Gilbert, 2006). Finally, it is noteworthy that tics wax and wane in frequency and intensity and migrate in location over time, often becoming more complex and peaking between the ages of 9 and 14 years (Gilbert, 2006). In the case of dyskinesias among youth at-risk for psychosis, there is evidence that the movements tend to increase in severity and frequency as the individual approaches the mean age of conversion to schizophrenia spectrum disorders (Mittal et al., 2008).
As revisions to the DSM are currently underway in preparation for the new edition (DSM V), we encourage greater attention to the important, though often subtle, distinctions among subtypes of movement abnormalities and their association with psychiatric syndromes.
67,017 citations
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TL;DR: A review of studies that measured compliance using EM confirmed that the prescribed number of doses per day is inversely related to compliance.
2,311 citations
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TL;DR: The findings suggest that mental disorders affect a significant number of children and adolescents worldwide and the pooled prevalence estimates and the identification of sources of heterogeneity have important implications to service, training, and research planning around the world.
Abstract: Background
The literature on the prevalence of mental disorders affecting children and adolescents has expanded significantly over the last three decades around the world. Despite the field having matured significantly, there has been no meta-analysis to calculate a worldwide-pooled prevalence and to empirically assess the sources of heterogeneity of estimates.
Methods
We conducted a systematic review of the literature searching in PubMed, PsycINFO, and EMBASE for prevalence studies of mental disorders investigating probabilistic community samples of children and adolescents with standardized assessments methods that derive diagnoses according to the DSM or ICD. Meta-analytical techniques were used to estimate the prevalence rates of any mental disorder and individual diagnostic groups. A meta-regression analysis was performed to estimate the effect of population and sample characteristics, study methods, assessment procedures, and case definition in determining the heterogeneity of estimates.
Results
We included 41 studies conducted in 27 countries from every world region. The worldwide-pooled prevalence of mental disorders was 13.4% (CI 95% 11.3–15.9). The worldwide prevalence of any anxiety disorder was 6.5% (CI 95% 4.7–9.1), any depressive disorder was 2.6% (CI 95% 1.7–3.9), attention-deficit hyperactivity disorder was 3.4% (CI 95% 2.6–4.5), and any disruptive disorder was 5.7% (CI 95% 4.0–8.1). Significant heterogeneity was detected for all pooled estimates. The multivariate metaregression analyses indicated that sample representativeness, sample frame, and diagnostic interview were significant moderators of prevalence estimates. Estimates did not vary as a function of geographic location of studies and year of data collection. The multivariate model explained 88.89% of prevalence heterogeneity, but residual heterogeneity was still significant. Additional meta-analysis detected significant pooled difference in prevalence rates according to requirement of funcional impairment for the diagnosis of mental disorders.
Conclusions
Our findings suggest that mental disorders affect a significant number of children and adolescents worldwide. The pooled prevalence estimates and the identification of sources of heterogeneity have important implications to service, training, and research planning around the world.
2,219 citations
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TL;DR: This practice parameter describes the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) based on the current scientific evidence and clinical consensus of experts in the field.
Abstract: This practice parameter describes the assessment and treatment of children and adolescents with attention-deficit/ hyperactivity disorder (ADHD) based on the current scientific evidence and clinical consensus of experts in the field. This parameter discusses the clinical evaluation for ADHD, comorbid conditions associated with ADHD, research on the etiology of the disorder, and psychopharmacological and psychosocial interventions for ADHD. J. Am. Acad. Child Adolesc. Psychiatry, 2007;46(7):894Y921. Key Words: attention-deficit/hyperactivity disorder, evaluation, treatment, practice parameter.
1,561 citations
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TL;DR: Estimates of ADHD prevalence and correlates in the World Health Organization World Mental Health Survey Initiative should be considered more seriously in future epidemiological and clinical studies than is currently the case.
Abstract: Background Little is known about the epidemiology of adult attention-deficit hyperactivity disorder (ADHD). Aims To estimate the prevalence and correlates of DSM-IV adult ADHD in the World Health Organization World Mental Health Survey Initiative. Method An ADHD screen was administered to respondents aged 18-44 years in ten countries in the Americas, Europe and the Middle East (n=11422). Masked clinical reappraisal interviews were administered to 154 US respondents to calibrate the screen. Multiple imputation was used to estimate prevalence and correlates based on the assumption of cross-national calibration comparability. Results Estimates of ADHD prevalence averaged 3.4% (range 1.2-7.3%), with lower prevalence in lower-income countries (1.9%) compared with higher-income countries (4.2%). Adult ADHD often co-occurs with other DSM-IV disorders and is associated with considerable role disability. Few cases are treated for ADHD, but in many cases treatment is given for comorbid disorders. Conclusions Adult ADHD should be considered more seriously in future epidemiological and clinical studies than is currently the case.
1,219 citations