Alonso Montoya

Attention deficit hyperactivity disorder in the European adult population: prevalence, disease awareness, and treatment guidelines

Abstract Background: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobiological disorder with childhood onset and persistence into adolescence and adulthood. Methods: Our literature review reports scientific publications and guidelines on the treatment of adult ADHD, with a particular focus on European countries, identified by literature searches in Medline and Embase. The final literature search was performed in July 2012, incorporating literature from 1974 to 2012. The primary research parameters were ‘Europe’ (including single European countries), ‘ADHD’, ‘attention deficit disorder’, ‘attention deficit’, ‘attention disorder’, and ‘hyperactivity’. Secondary search parameters were ‘comorbid’, ‘epidemiology’ or ‘prevalence’, ‘disease management’, ‘drug therapy’, or ‘therapy’. The main searches were also limited to adults and English language publications. The papers identified by this literature review were selected for inclusion by consensus of the authors based on clinical relevance. Results: Appropriate resources for the diagnosis and treatment of adult ADHD in Europe are scarce, and many cases go untreated, particularly because of the frequent presence of psychiatric comorbidities. Apart from atomoxetine, and an extended-release form of methylphenidate in Germany, no other medications have been approved for starting treatment in adult ADHD patients in the European Union. However, a variety of stimulant and non-stimulant medications are used off-label, and a number of studies have confirmed that these medications are well tolerated and effective in adult patients with ADHD. Conclusions: Our results emphasize the need for broader access to effective treatments for adult ADHD patients in Europe.

Validation of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) in a naturalistic sample of 278 patients with acute psychosis and agitation in a psychiatric emergency room

BackgroundDespite the wide use of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) in a clinical setting to assess agitated patients, a validation study to evaluate its psychometric properties was missing.MethodsData from the observational NATURA study were used. This research describes trends in the use of treatments in patients with acute psychotic episodes and agitation seen in emergency departments. Exploratory principal component factor analysis was performed. Spearmans correlation and regression analyses (linear regression model) as well as equipercentile linking of Clinical Global Impression of Severity (CGI-S), Agitation and Calmness Evaluation Scale (ACES) and PANSS-EC items were conducted to examine the scales diagnostic validity. Furthermore, reliability (Cronbachs alpha) and responsiveness were evaluated.ResultsFactor analysis resulted in one factor being retained according to eigenvalue ≥1. At admission, the PANSS-EC and CGI-S were found to be linearly related, with an average increase of 3.4 points (p < 0.001) on the PANSS-EC for each additional CGI-S point. The PANSS-EC and ACES were found to be linearly and inversely related, with an average decrease of 5.5 points (p < 0.001) on the PANSS-EC for each additional point. The equipercentile method shows the poor sensitivity of the ACES scale. Cronbachs alpha was 0.86 and effect size was 1.44.ConclusionsThe factorial analyses confirm the unifactorial structure of the PANSS-EC subscale. The PANSS-EC showed a strong linear correlation with rating scales such as CGI-S and ACES. PANSS-EC has also shown an excellent capacity to detect real changes in agitated patients.

Evaluation of atomoxetine for first-line treatment of newly diagnosed, treatment-naïve children and adolescents with attention deficit/hyperactivity disorder.

Abstract Objective: To test the hypothesis that first-line treatment with atomoxetine provides superior efficacy than placebo for up to 12 weeks in improving the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). Research design and methods: This double-blind, randomized, placebo-controlled, parallel clinical trial included 151 treatment-naïve children (n = 113) and adolescents (n = 38) with newly diagnosed (≤3 months) ADHD. Atomoxetine dose was uptitrated from 0.5 to 1.2 mg/kg/day after two weeks. Outcome assessments included the ADHD Rating Scale-IV-Parent-reported Investigator-rated (ADHDRS-IV-Parent:Inv), the Clinical Global Impression of Severity of ADHD (CGI-ADHD-S), and the incidence of adverse events. Mixed-model repeated measures analysis was used to compare scale score changes between groups. Clinical trial registration: Trial registered at www.clinicaltrials.gov (study internal code: B4Z-XM-LYDM, identifier: NCT00191945). Results: Most patients were male (79.2%), of caucasian origin (96.0%) and severely ill (72.5%). Their mean age was 10.3 years. Atomoxetine-treated patients showed greater reductions from baseline to week 12 of total ADHDRS-IV-Parent:Inv score than placebo-treated patients (least square mean difference: −7.9 [95% CI: −11.0 to −4.8], corresponding to a large effect size of 0.8). Between-group mean differences increased progressively with treatment exposure from week 6 to 12 (−2.7 [−4.9 to −0.6] for total and −1.6 [−2.9 to −0.3] for inattention scores). At the end of the study, 50% of atomoxetine-treated patients (14% with placebo) showed a reduction ≥40% in total ADHDRS-IV-Parent:Inv score, and only 29% (46% with placebo) were severely ill (by CGI-ADHD-S). Treatment-related adverse events were significantly more frequent with atomoxetine (65.0%) than with placebo (37.3%), the most frequent being decreased appetite and somnolence. Only one case of decreased appetite was rated as severe. No patient discontinued treatment because of adverse events. Conclusions: A continued improvement of symptoms is expectable until 12 weeks in treatment-naïve ADHD patients treated with atomoxetine as first-line medication. Chief limitations are the small, national sample size and the absence of data beyond the 12-week time-point.

The noradrenergic paradox: implications in the management of depression and anxiety

Both major depressive disorder and the anxiety disorders are major causes of disability and markedly contribute to a significant global burden of the disease worldwide. In part because of the significant socioeconomic burden associated with these disorders, theories have been developed to specifically build clinical treatment approaches. One such theory, the monoaminergic hypothesis, has led to the development of several generations of selective and nonselective inhibitors of transporters of serotonin and norepinephrine, with the goal of augmenting monoaminergic transmission. These efforts have led to considerable success in the development of antidepressant therapeutics. However, there is a strong correlation between enhanced noradrenergic activity and fear and anxiety. Consequently, some physicians have expressed concerns that the same enhanced noradrenergic activity that alleviates depression could also promote anxiety. The fact that the serotonergic and noradrenergic reuptake inhibitors are successfully used in the treatment of anxiety and panic disorders seems paradoxical. This review was undertaken to determine if any clinical evidence exists to show that serotonergic and noradrenergic reuptake inhibitors can cause anxiety. The PubMed, EMBASE, and Cochrane Library databases were searched, and the results limited to randomized, double-blind, placebo-controlled studies performed in nongeriatric adults and with clear outcome measures were reported. Based on these criteria, a total of 52 studies were examined. Patients in these studies suffered from depression or anxiety disorders (generalized and social anxiety disorders, panic disorder, and posttraumatic stress disorder). The large majority of these studies employed venlafaxine or duloxetine, and the remainder used tri-cyclic antidepressants, atomoxetine, or reboxetine. All the studies reported clinically significant alleviation of depressive and/or anxious symptoms by these therapeutics. In none of these studies was anxiety a treatment-emergent adverse effect. This review argues against the impression that enhanced generalized noradrenergic activity promotes the emergence of anxiety.

Changes of urine dihydroxyphenylglycol to norepinephrine ratio in children with attention-deficit hyperactivity disorder (ADHD) treated with atomoxetine.

This study investigated changes in the urine dihydroxyphenylglycol to norepinephrine ratio in patients with attention-deficit hyperactivity disorder (ADHD) treated with atomoxetine. The possible relationship with clinical response was also explored. Newly ADHD diagnosed, treatment-naïve children or adolescents were double-blindly randomized (2:1) to atomoxetine (n = 28) or placebo (n = 13). The dihydroxyphenylglycol to norepinephrine ratio decreased in both groups, showing significantly greater changes with atomoxetine than with placebo at week 6 (-42% versus -14%; P = .001), when dosed at 1.2 mg/kg/day, than at week 2 (-20% versus -2%; P = .118) with a dose of 0.5 mg/kg/day. Although the significant dihydroxyphenylglycol to norepinephrine ratio decrease with atomoxetine indicated norepinephrine transporter blockade, no association with ADHD clinical response (ADHD Rating Scale-IV-Parent:Investigator) was found. Therefore, dihydroxyphenylglycol to norepinephrine ratio might be a useful pharmacodynamic/pharmacokinetic biomarker, although not sufficiently sensitive to predict clinical efficacy. It remains a possibility that this ratio might have value to facilitate personalized atomoxetine pharmacotherapy in ADHD patients.

Evaluating internet information on attention-deficit/hyperactivity disorder (ADHD) treatment: Parent and expert perspectives

BACKGROUND The Internet is increasingly used as a source of health-related information. The objective of this study was to assess the quality of web-based information on treatments for attention-deficit/hyperactivity disorder (ADHD). METHODS Sixteen expert health professionals in ADHD and 35 parents of paediatric patients with a recent diagnosis of ADHD assessed the information contained in the 10 highest ranked websites in Spanish, using the Spanish version of the DISCERN tool - a validated questionnaire designed to assess the quality and reliability of web-based information on treatment choices (rating scores from 15 to 75). RESULTS DISCERN scores given by parents and experts were low (total mean scores [standard deviation]: 35.9 [13.1] and 43.4 [13.7], respectively) and inter-rater agreement was poor/moderate (weighted kappa for the global assessment between -0.69 and +0.93, average = 0.29). There was a significant change on the ADHD-knowledge and motivation for treatment (ADHD-KMT) basic knowledge sub-scale score after the assessment of the different websites by parents (total mean scores [standard deviation]: 49.09 [9.46] and 63.21 [9.45]). CONCLUSIONS Despite a poor/moderate inter-rater agreement between parent and expert opinions, all agreed that the quality of the web-based information on treatment choices for ADHD is generally poor.

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.

Clinical characteristics of agitated psychotic patients treated with an oral antipsychotics attended in the emergency room setting: NATURA study.

Purpose. Prospective observational study to describe the clinical characteristics of patients with acute psychosis and agitation who receive oral psychopharmacological treatment at psychiatric emergency services (PES). Methods. A total of 278 patients with acute psychosis and agitation were admitted to PES and received oral psychopharmacological treatment. Diagnosis at admission, agitation level at entry and discharge, use of mechanical restraints, pharmacological and time to reintervention were prospectively explored. Severity of the disease was evaluated according to the Positive and Negative Syndrome Scale–Excitement Component (PANSS-EC), Agitation Calmness Evaluation Scale (ACES) and Clinical Global Impression-Severity (CGI-S) at admission, before first reintervention (if any) and at discharge from PES. Results. Most prevalent diagnoses were schizophrenia (77%) and bipolar disorder (12.2%). Mean (SD) scores in rating scales at baseline and at discharge were, respectively: PANSS-EC, 20.38(5.3) and 13.04 (5.5); CGI-S, 3.86(1.1) and 2.17(0.9); and ACES, 2.35(0.6) and 3.60(1.1). A total of 21.6% (60/278) of the patients required mechanical restraints and 38.1% (106/278) reintervention. From the emergency room, 20.5% patients went home while 71.2% were transferred to inpatient units. Conclusion. Clinical characteristics of psychotic agitated patients may help in deciding which type of treatment should be used and may be useful for the design of future prospective trials to explore treatment of agitation.

Fast vs. slow switching from stimulants to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE To compare fast versus slow switching from stimulants to atomoxetine (ATX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS This was a randomized, controlled, open-label study in 6-16-year-old ADHD patients, previously treated with stimulants and cross-titrated (fast switch, over 2 weeks, or slow switch, over 10 weeks) to ATX because of unsatisfactory response and/or adverse events. Study duration was 14 weeks with an ATX standard target dose of 1.2 mg/kg/day. Primary measure was the change from baseline in the investigator-rated ADHD-Rating Scale (ADHD-RS) at weeks 2 and 10. Secondary measures included Global Impression of Perceived Difficulties (GIPD) and Child Health and Illness Profile-Child Edition (CHIP-CE). RESULTS The majority of the 111 patients were male (83.8%, n=93) and mean (SD) age was 11.5 (2.38) years. Mean baseline ADHD-RS total score was 36.0 in the fast and 38.0 in the slow group. Adjusted mean change after 2 weeks was -8.1 (-10.1; -6.1) in the fast and -8.0 (-9.9;-6.0) in the slow group (p=0.927), and after 10 weeks -15.0 (-17.4;-12.6) and -14.3 (-16.7;-12.0), respectively, (p=0.692). GIPD scores did not show differences between groups. Significant differences at week 10 were found in the CHIP-CE achievement domain favoring slow (p=0.036) and the comfort domain favoring fast cross-titration (p=0.030). No significant differences were found for adverse events, and differences for systolic blood pressure (BP) and weight were not considered clinically relevant. CONCLUSIONS ADHD-RS and GIPD scores improved in both switching groups. No clinically relevant differences between fast and slow switching from stimulants to ATX were found.