Javier Quintero

Complexity analysis of spontaneous brain activity in attention-deficit/hyperactivity disorder: diagnostic implications.

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is defined as the most common neurobehavioral disorder of childhood, but an objective diagnostic test is not available yet to date. Neurophychological, neuroimaging, and neurophysiological research offer ample evidence of brain and behavioral dysfunctions in ADHD, but these findings have not been useful as a diagnostic test. METHODS Whole-head magnetoencephalographic recordings were obtained from 14 diagnosed ADHD patients and 14 healthy children during resting conditions. Lempel-Ziv complexity (LZC) values were obtained for each channel and child and averaged in five sensor groups: anterior, central, left lateral, right lateral, and posterior. RESULTS Lempel-Ziv complexity scores were significantly higher in control subjects, with the maximum value in anterior region. Combining age and anterior complexity values allowed the correct classification of ADHD patients and control subjects with a 93% sensitivity and 79% specificity. Control subjects showed an age-related monotonic increase of LZC scores in all sensor groups, while children with ADHD exhibited a nonsignificant tendency toward decreased LZC scores. The age-related divergence resulted in a 100% specificity in children older than 9 years. CONCLUSIONS Results support the role of a frontal hypoactivity in the diagnosis of ADHD. Moreover, the age-related divergence of complexity scores between ADHD patients and control subjects might reflect distinctive developmental trajectories. This interpretation of our results is in agreement with recent investigations reporting a delay of cortical maturation in the prefrontal cortex.

Underdiagnosis of Attention-Deficit/Hyperactivity Disorder in Adult Patients: A Review of the Literature

Objective: To raise awareness of attention-deficit/hyperactivity disorder (ADHD) as an underdiagnosed, undertreated, often comorbid, and debilitating condition in adults. Data Sources: PubMed was searched using combinations of keywords, including ADHD, adult, diagnosis, identify, prevalence, and comorbid, to find articles published between 1976 and 2013. Study Selection: In total, 99 articles were selected for inclusion on the basis of their relevance to the objective and importance to and representation of ADHD research, including international guidelines for adults with ADHD. Results: In a large proportion of children with ADHD, symptoms persist into adulthood. However, although adults with ADHD often experience chaotic lifestyles, with impaired educational and vocational achievement and higher risks of substance abuse and imprisonment, many remain undiagnosed and/or untreated. ADHD is usually accompanied by other psychiatric comorbidities (such as major depressive disorder, anxiety disorder, and alcohol abuse). Indeed, adults with ADHD are more likely to present to a psychiatric clinic for treatment of their comorbid disorders than for ADHD, and their ADHD symptoms are often mistaken for those of their comorbidities. Untreated ADHD in adults with psychiatric comorbidities leads to poor clinical and functional outcomes for the patient even if comorbidities are treated. Effective treatment of adults’ ADHD improves symptoms, emotional lability, and patient functioning, often leading to favorable outcomes (eg, safer driving, reduced criminality). A few medications have now been approved for use in adults with ADHD, while a multimodal approach involving psychotherapy has also shown promising results. Conclusions General psychiatrists should familiarize themselves with the symptoms of ADHD in adults in order to diagnose and manage ADHD and comorbidities appropriately in these patients.

A Phase 3, Multicenter, Open-Label, 12-Month Extension Safety and Tolerability Trial of Lisdexamfetamine Dimesylate in Adults With Binge Eating Disorder

Background A 12-month, open-label extension study assessed the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in adults with binge eating disorder (BED). Methods Adults (aged 18–55 y) with BED who completed 1 of 3 antecedent studies were enrolled in a 52-week, open-label extension study (dose optimization, 4 weeks [initial titration dose, 30-mg LDX; target doses, 50- or 70-mg LDX]; dose maintenance, 48 weeks). Safety evaluations included the occurrence of treatment-emergent adverse events (TEAEs), vital sign and weight assessments, and Columbia-Suicide Severity Rating Scale responses. Results Of the 604 enrolled participants, 599 (521 women and 78 men) comprised the safety analysis set, and 369 completed the study. Mean (SD) LDX exposure was 284.3 (118.84) days; cumulative LDX exposure duration was 12 months or longer in 344 participants (57.4%). A total of 506 participants (84.5%) reported TEAEs (TEAEs leading to treatment discontinuation, 54 [9.0%]; severe TEAEs, 42 [7.0%]; serious TEAEs, 17 [2.8%]). Treatment-emergent adverse events reported in greater than or equal to 10% of participants were dry mouth (27.2%), headache (13.2%), insomnia (12.4%), and upper respiratory tract infection (11.4%). Mean (SD) changes from antecedent study baseline in systolic and diastolic blood pressure, pulse, and weight at week 52/early termination (n = 597) were 2.19 (11.043) and 1.77 (7.848) mm Hg, 6.58 (10.572) beats per minute, and −7.04 (7.534) kg, respectively. On the Columbia-Suicide Severity Rating Scale, there were 2 positive responses for any active suicidal ideations; there were no positive responses for suicidal behavior or completed suicides. Conclusions In this 12-month, open-label, extension study, the long-term safety and tolerability of LDX in adults with BED were generally consistent with its established profile for attention-deficit/hyperactivity disorder.

MEG analysis of neural dynamics in attention-deficit/hyperactivity disorder with fuzzy entropy

The aim of this study was to analyze the neural dynamics in attention-deficit/hyperactivity disorder (ADHD). For this purpose, magnetoencephalographic (MEG) background activity was analyzed using fuzzy entropy (FuzzyEn), an entropy measure that quantifies signal irregularity, in 13 ADHD patients and 14 control children. Additionally, relative power (RP) was computed in conventional frequency bands (delta, theta, alpha, beta and gamma). FuzzyEn results showed that MEG activity was more regular in ADHD patients than in controls. Moreover, we found an increase of power in delta band and a decrease in the remaining frequency bands. Statistically significant differences (p-values <0.05; nonparametric permutation test for multiple comparisons) were detected for FuzzyEn in the posterior and left temporal regions, and for RP in the posterior, anterior and left temporal regions. Our results support the hypothesis that ADHD involves widespread functional brain abnormalities, affecting more areas than fronto-striatal circuits, such as the left temporal and posterior regions.

Variation in Presentation, Diagnosis, and Management of Children and Adolescents With ADHD Across European Countries.

Objective: To characterize differences in presentation, diagnosis, and management of children/adolescents with ADHD in six European countries. Method: Physicians abstracted clinical records for patients aged 6 to 17 years, diagnosed from 2004 to 2007 and treated for ≥2 years. Documentation included impairment due to core ADHD symptoms and additional ADHD symptoms/behaviors at diagnosis, diagnostic approach, and treatment modality. Results: Study included 779 patients treated by 340 physicians. Prevalence of ADHD subtypes (inattention, hyperactivity/impulsivity, or combined) was similar across countries. Mean scores for core and noncore symptom impairment varied and were highest in Italy and the United Kingdom. Variability was noted in diagnostic approach; 95% of physicians in the Netherlands used Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria versus 10% in Germany. Differences were reported for initial treatment modality, treatment switching, and physician-reported treatment outcomes. Conclusion: European countries varied in diagnostic approaches and practice management of children/adolescents with ADHD.

Access to diagnosis, treatment, and supportive services among pharmacotherapy-treated children/adolescents with ADHD in Europe: data from the Caregiver Perspective on Pediatric ADHD survey

Background Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders and negatively impacts caregivers’ lives. Factors including barriers to accessing care, dissatisfaction with support services, and lack of caregiver resources may contribute to this. Objectives To report caregivers’ experiences of ADHD diagnosis, behavioral therapy (BT), and supportive care for children/adolescents with ADHD. Methods The Caregiver Perspective on Pediatric ADHD (CAPPA) survey included caregivers of children/adolescents (6–17 years) from ten European countries who were currently receiving/had received ADHD pharmacotherapy in the previous 6 months. Caregivers reported experiences of obtaining an ADHD diagnosis, access to BT, availability of caregiver resources, and level of health care/school support. Pan-EU and country-specific descriptive statistics are reported; responses were compared across countries. Results Of 3,616 caregivers, 66% were female. Mean age of children/adolescents was 11.5 years; 80% were male. Mean time from the first doctor visit to diagnosis was 10.8 (95% confidence interval 10.2, 11.3) months; 31% of caregivers reported the greatest degrees of difficulty in obtaining an ADHD diagnosis; 44% of children/adolescents did not receive BT. Forty-seven percent of caregivers reported that sufficient resources were available, 44% were “very satisfied”/“satisfied” with medical care, and 50% found health care providers “very supportive”/“somewhat supportive”. Mainstream schools were attended by 82% of children/adolescents. Of those, 67% of caregivers thought schools could help more with the child/adolescent’s ADHD and 48% received extra help/special arrangement. Results varied significantly between countries (P<0.001, all parameters). Conclusion Almost a third of caregivers reported a high degree of difficulty in obtaining an ADHD diagnosis for their child/adolescent, less than half felt that sufficient resources were available, and gaps in support from health care providers/schools were identified. Findings underscore the need to improve access to diagnosis and provision of supportive services to enable better standards of care, and potentially reduce the impact of child/adolescent ADHD on caregivers’ lives.

Factors associated with caregiver burden among pharmacotherapy-treated children/adolescents with ADHD in the Caregiver Perspective on Pediatric ADHD survey in Europe

Background Burden on caregivers of children/adolescents with attention-deficit/hyperactivity disorder (ADHD) is multidimensional, but incompletely understood. Objective To analyze caregiver burden across the concepts of work, social/family life, and parental worry/stress, in relation to selected contributing factors. Methods The online Caregiver Perspective on Pediatric ADHD survey was fielded in ten European countries. Analysis included children/adolescents (6–17 years) who were receiving/had received ADHD pharmacotherapy in the previous 6 months. Caregivers recorded their child’s/adolescent’s symptoms “on”/“off” medication (ie, when the caregiver reported that the child/adolescent forgot/chose not to take medication, before the onset of medication effect, or medication worn off). Effects of ADHD severity, comorbidities, and medication adherence on each burden outcome were assessed (multiple regression models). Results In total, 2,326 caregivers were included (children/adolescents’ mean age: 11.5 years, 80% male). Caregivers reported missed/altered work, avoiding social activity, increased parental worry/stress, and strain on family life, despite using ADHD pharmacotherapy. Child/adolescent comorbidities and ADHD severity were significantly related to all burden concepts measured; the strongest comorbidity associations were with altered work (odds ratios [ORs] =1.68 [95% confidence interval {CI} 1.33, 2.12], 1.87 [1.37, 2.54], 3.47 [2.51, 4.78] for 1, 2, 3+ comorbidities, respectively) and planning the day around the child/adolescent (OR =1.42 [95% CI 1.17, 1.72], 1.73 [1.33, 2.15], 2.65 [1.99, 3.53]); the strongest severity associations were: quitting a job (OR =1.41 [95% CI 1.26, 1.59]) and planning a day around the child/adolescent (OR =1.26 [95% CI 1.20, 1.32]). Increased medication adherence was most associated with reducing the caregiver burden for altered work (OR =0.57 [95% CI 0.45, 0.72]), worrying about how they are being perceived as a parent (OR =0.68 [0.56, 0.83]), and avoiding social activity (OR =0.56 [0.45, 0.68]), but not family or stress burden. Conclusion Burdens related to work, social activity, family life, and parental worry/stress were experienced by the caregivers of children/adolescents with ADHD, despite using ADHD pharmacotherapy. Better understanding of clinical/treatment characteristics most associated with the components of caregiver burden may help improve ADHD management and may ease caregiver burden.

Cluster-randomized, controlled 12-month trial to evaluate the effect of a parental psychoeducation program on medication persistence in children with attention-deficit/hyperactivity disorder

Background This multicenter, cluster-randomized, nonblinded study evaluated the effect of parental psychoeducation on medication persistence among children and adolescents with newly diagnosed attention-deficit/hyperactivity disorder (ADHD). Methods Patients received standard medication alone or medication plus a parental psychoeducation program, and were followed for 12 months. The primary endpoint was time to withdrawal or termination of medication due to any cause. Secondary endpoints included change in ADHD symptom severity, functional outcome, program satisfaction, and safety. Results A total of 208 patients completed the study, which was terminated early because recruitment had ceased. At 12 months, there was no significant difference between the psychoeducation and control groups in the proportion of patients who discontinued pharmacologic treatment (13.2% versus 14.3%, respectively; size effect −0.3, P=0.34; hazard ratio 0.72, 95% confidence interval 0.36–1.43). Psychoeducation was associated with a significantly greater improvement in ADHD symptoms but not in functional outcome. Parental satisfaction with psychoeducation was high, and satisfaction with pharmacologic treatment was significantly greater in the psychoeducation group. There were no safety concerns. Conclusion No significant advantage for parental psychoeducation plus medication over medication alone in terms of time to medication withdrawal was observed. Psychoeducation had inconsistent but interesting effects on other outcomes.

Caregiver perspective on pediatric attention-deficit/hyperactivity disorder: medication satisfaction and symptom control

The caregiver perspective on pediatric attention-deficit/hyperactivity disorder (ADHD) study (CAPPA) was a web-based, cross-sectional survey of caregivers of children and adolescents (6–17 years of age) with ADHD and was conducted in 10 European countries. CAPPA included caregiver assessments of global medication satisfaction, global symptom control, and satisfaction with ADHD medication attributes. Overall, 2,326 caregiver responses indicated that their child or adolescent was currently receiving ADHD medication and completed the “off medication” assessment required for inclusion in the present analyses. Responses to the single-item global medication satisfaction question indicated that 88% were satisfied (moderately satisfied to very satisfied) with current medication and 18% were “very satisfied” on the single-item question. Responses to the single-item global symptom control question indicated that 47% and 19% of caregivers considered their child or adolescent’s symptoms to be “controlled” or “very well controlled”, respectively. Significant variations in response to the questions of medication satisfaction and symptom control were observed between countries. The correlation between the global medication satisfaction and global symptom control questions was 0.677 (P<0.001). Global medication satisfaction was significantly correlated (P<0.001) with all assessed medication attributes, with the highest correlations observed for symptom control (r=0.601) and effect duration (r=0.449). Correlations of medication attributes with global symptom control were generally lower than with global medication satisfaction but were all statistically significant (P<0.001). CAPPA medication satisfaction and symptom control were also significantly correlated (P<0.001) with symptom control as based on the ADHD-Rating Scale-IV symptom score and the number of bad days per month when on medication. In conclusion, caregiver responses in this European sample suggest that current treatment could potentially be improved. The observed correlations of global medication satisfaction with global symptom control and other CAPPA assessments, including medication attributes, provide support for the inter-connectivity of the medication satisfaction and symptom control.

Emotional Intelligence as an Evolutive Factor on Adult With ADHD

Objective: ADHD adults exhibit deficits in emotion recognition, regulation, and expression. Emotional intelligence (EI) correlates with better life performance and is considered a skill that can be learned and developed. The aim of this study was to assess EI development as ability in ADHD adults, considering the effect of comorbid psychiatric disorders and previous diagnosis of ADHD. Method: Participants (n = 116) were distributed in four groups attending to current comorbidities and previous ADHD diagnosis, and administered the Mayer–Salovey–Caruso Emotional Intelligence Test version 2.0 to assess their EI level. Results: ADHD adults with comorbidity with no previous diagnosis had lower EI development than healthy controls and the rest of ADHD groups. In addition, ADHD severity in childhood or in adulthood did not influence the current EI level. Conclusion: EI development as a therapeutic approach could be of use in ADHD patients with comorbidities.