Incidence and risk of attention-deficit hyperactivity disorder in children with amblyopia: A nationwide cohort study.

IMPORTANCE: The association between visual deficits and attention disorders has been reported but remains unproven. BACKGROUND: The objective of this study was to evaluate the risk of attention-deficit hyperactivity disorder (ADHD) in children with amblyopia. DESIGN: Population-based, cohort study. PARTICIPANTS: The dataset from the Taiwan National Health Insurance Research Database in 2000 to 2010. METHODS: A total of 6817 patients aged <18 years with newly diagnosed amblyopia were identified. Four age- and sex-matched controls without amblyopia were included for each patient, that is, 27268 controls. MAIN OUTCOME MEASURES: The primary outcome was the risk of ADHD. The secondary outcomes were age at ADHD onset and use of ADHD medication. RESULTS: During a mean observation period of 7.18 years, the incidence of ADHD per 1000 person-years was 7.02 in the amblyopia group and 4.61 in the control group (P < 0.0001). The ADHD risk in the amblyopia group was 1.81 times that in the control group (hazard ratio 1.81; 95% confidence interval 1.59-2.06). After stratification by amblyopia subtype, the greatest risk was in the deprivation type (hazard ratio 2.14; 95% confidence interval 1.56-2.92) followed by the strabismic (hazard ratio 2.09; 95% confidence interval 1.15-3.79) and refractive (hazard ratio 1.76; 95% confidence interval 1.54-2.02) types. Age at ADHD onset was younger in the amblyopia group (median 8.14 vs 8.45 years; P = 0.0096). The average duration of neuropsychiatric medication use was comparable between groups (P = 0.98). CONCLUSIONS AND RELEVANCE: The ADHD risk is higher in children with amblyopia.

Risk of Type 2 Diabetes in Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder: A Nationwide Longitudinal Study.

BACKGROUND: Studies have suggested there is an association between attention-deficit/hyperactivity disorder (ADHD) and type 2 diabetes mellitus (DM)-related risk factors, such as obesity, hypertension, and dyslipidemia. However, the association between ADHD and type 2 DM remains unknown. METHODS: Using the Taiwan National Health Insurance Research Database, we enrolled 35,949 adolescents and young adults with ADHD (ICD-9-CM code: 314) and 71,898 (1:2) age- and sex-matched controls from 2002 through 2009 and followed up with them until the end of 2011. Participants who developed type 2 DM during the follow-up period were identified. RESULTS: Adolescents (hazard ratio [HR] = 2.83; 95% CI, 1.96-4.09) and young adults (HR = 3.28; 95% CI, 1.41-7.63) with ADHD had a higher risk of developing type 2 DM than did the controls after adjustment for demographic characteristics, use of ADHD medications and atypical antipsychotics, and medical comorbidities. Individuals with ADHD had a shorter mean ± SD duration between enrollment and onset of type 2 DM (3.17 ± 2.33 vs 4.08 ± 2.11 years, P = .004) during the follow-up compared with the controls. Sensitivity analyses after excluding first-year (HR = 2.36; 95% CI, 1.65-3.38) and first-3-year (HR = 1.92; 95% CI, 1.19-3.09) observation periods were consistent. Long-term use of atypical antipsychotics was associated with a higher likelihood of subsequent type 2 DM (HR = 2.82, 95% CI, 1.74-4.58). DISCUSSION: Adolescents and young adults with ADHD were more likely than non-ADHD controls to develop type 2 DM in later life. In addition, those with ADHD taking atypical antipsychotics exhibited a higher risk. Although correlation does not equal causation, our findings merit further study about the relationship between ADHD and type 2 DM.

Efficacy of Hippotherapy Versus Pharmacotherapy in Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial.

OBJECTIVES: Pharmacotherapy among children with attention-deficit/hyperactivity disorder (ADHD) is effective, but many patients suffer from secondary psychiatric problems even after improvement of ADHD core symptoms. Hippotherapy have been used as adjunct treatment options for physical and psychosocial rehabilitation as well as to ameliorate core symptoms. The aim of this study was to investigate the effects of Hippotherapy versus pharmacotherapy for children with ADHD. DESIGN: Thirty-four participants with ADHD were randomly assigned at a 1:1 ratio to either 24 sessions of a twice-weekly hippotherapy or pharmacotherapy. To assess therapeutic effects, the ADHD Rating Scale (ARS) was used pretreatment and posttreatment as the primary outcome measure. Secondary outcomes included the Child Behavior Checklist (CBCL), Self-Esteem Scale (SES), Pediatric Quality of Life Inventory (PedsQL) child and parent report version, Developmental Coordination Disorder Questionnaire (DCDQ), Clinical Global Impressions-Severity (CGI-S), and quantitative electroencephalography. RESULTS: Both groups showed marked improvements in ADHD symptoms, CGI-S. No significant differences between groups were detected regarding treatment outcome except thought problem subscales of CBCL. Twelve weeks of hippotherapy improved attention, impulsivity/hyperactivity, and quality of life. CONCLUSION: This trial is promising, but further studies are required to evaluate the long-term clinical effectiveness of hippotherapy. The study is registered with ClinicalTrials.gov, number NCT 02482649.

Miscellaneous treatments for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere. OBJECTIVES: To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers (16 July 2015 and 26 April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We included reports if they were randomised controlled trials (RCTs) dealing with people with antipsychotic-induced TD and schizophrenia or other chronic mental illnesses who remained on their antipsychotic medication and had been randomly allocated to the interventions listed above versus placebo, no intervention, or any other intervention. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE. MAIN RESULTS: We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'. AUTHORS' CONCLUSIONS: This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia. However, since only one RCT has investigated each one of these compounds, we are awaiting results from ongoing trials to confirm these results. Results for the remaining interventions covered in this review must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.

Fatigue in Patients with Major Depressive Disorder: Prevalence, Burden and Pharmacological Approaches to Management.

Fatigue is a frequently reported symptom in major depressive disorder, occurring in over 90% of patients. Clinical presentations of fatigue within major depressive disorder encompass overlapping physical, cognitive and emotional aspects. While this review addresses the epidemiology, burden, functional impact and management of fatigue in major depressive disorder, the main focus is on available pharmacotherapy options and their comparative efficacies. Our review of the effects of pharmacological treatments on fatigue in major depressive disorder found that medications with dopaminergic and/or noradrenergic action such as modafinil, flupenthixol and atomoxetine were most effective in improving symptoms of fatigue and low energy. However, significant variation across studies in assessment tools and study inclusion/exclusion criteria may have contributed to inconsistent findings. The efficacy of non-pharmacological interventions is also discussed, including light therapy and exercise.

Mindfulness vs psychoeducation in adult ADHD: a randomized controlled trial.

BACKGROUND: Mindfulness training is a promising treatment approach in adult ADHD. However, there has not yet been a randomized controlled trial comparing mindfulness to an active control condition. In this study, we assessed the efficacy of a mindfulness training program (MAP) compared to structured psychoeducation (PE). METHODS: After randomization 81 medication-free adult ADHD patients participated either in an 8-week MAP or PE group program. At baseline (T1), after 8 weeks (T2) and after 8 months (T3), severity of ADHD and associated symptoms (depression, general psychopathology, quality of life) were measured with the Conner's ADHD Rating Scales (CAARS), the Beck Depression Inventory (BDI), the Brief Symptom Inventory (BSI) and the SF-36 by self and blind observer ratings. RESULTS: Both groups showed significant pre-post improvements in observer-rated Inattention scale (p < .001, partial η2 = 0.18) and in associated symptomatology, which persisted through 6 months of follow-up. There were no significant differences regarding symptom reduction between the treatment groups. Women benefited more compared to men irrespective of treatment group. Men showed the most pronounced changes under MAP. CONCLUSIONS: In the current study, MAP was not superior to PE regarding symptom reduction in adult ADHD. Both interventions, mindfulness meditation and PE, were efficacious in reducing symptom load in adult ADHD. Furthermore in exploratory post hoc tests the study provides evidence for a potential gender-specific treatment response in adult ADHD.

Relationships Between Functional Outcomes and Symptomatic Improvement in Atomoxetine-Treated Adult Patients with Attention-Deficit/Hyperactivity Disorder: Post Hoc Analysis of an Integrated Database.

BACKGROUND: Atomoxetine treatment is associated with improvements in functional outcomes in patients with attention-deficit/hyperactivity disorder (ADHD), although relationships between improvements in these outcomes and reductions in ADHD symptoms have not been comprehensively investigated in adults. OBJECTIVES: The aim of this study was to assess relationships between functional outcomes and ADHD symptoms (primary objective), and to assess time courses of changes in functional outcomes from baseline to weeks 10 and 24 (secondary objective). METHODS: We analyzed data pooled from seven Eli Lilly-sponsored placebo-controlled trials of atomoxetine in adults with ADHD that had Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version (CAARS-Inv:SV) total scores and functional outcome data at baseline and at week 10. Two trials also had these data at week 24. Patients were included in these pooled analyses if they had a CAARS-Inv:SV total score at baseline and at one or more post-baseline visits at weeks 10 or 24, or had post-baseline scores that would allow missing scores at weeks 10 or 24 to be imputed. To address the primary objective, changes in functional outcomes during treatment with atomoxetine versus placebo were assessed using last observation carried forward (LOCF) analysis of covariance (ANCOVA) and mixed-effects model repeated measures (MMRM) analysis, and correlations between score changes in CAARS-Inv:SV total and functional outcomes were assessed using Spearman's rank correlation coefficient (r) at weeks 10 and 24. The secondary objective was addressed using MMRM. RESULTS: At baseline, patients generally had moderately severe or worse ADHD symptoms (based on CAARS-Inv:SV total scores) and impaired functional outcomes (based on Adult ADHD Quality-of-Life [AAQoL], Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A], Sheehan Disability Scale [SDS], and 36-item Short-Form Health Survey [SF-36] scores). These baseline characteristics were comparable in the atomoxetine and placebo groups. For atomoxetine versus placebo, statistically significant improvements were detected in AAQoL total and subscores at weeks 10 and 24, and in BRIEF-A Self-Report scores at week 10, but not in BRIEF-A Informant Report or SDS scores at week 10 (no BRIEF-A or SDS data were available at week 24), and not in SF-36 at weeks 10 or 24. All functional improvements were gradual. During treatment with atomoxetine, there were moderate correlations between reductions in CAARS-Inv:SV total scores and increases in AAQoL total and subscores at weeks 10 and 24 (r range -0.58 to -0.39; n = 394-545), and also with reductions in BRIEF-A Self-Report at week 10 (r = 0.49; n = 256). With placebo, moderate correlations were also found between reductions in CAARS-Inv:SV total scores and increases in AAQoL total and subscores at weeks 10 and 24 (r range -0.56 to -0.28; n = 321-542), and with reductions in BRIEF-A Self-Report at week 10 (r = 0.49; n = 271). However, correlations between changes in CAARS-Inv:SV and BRIEF-A Informant at week 10 were low for atomoxetine-treated patients (r = 0.25; n = 65), moderate with placebo (r = 0.42; n = 72), and there were low/no correlations between changes in CAARS-Inv:SV and functional outcome rating scales that are not specific to ADHD; that is, for atomoxetine-treated patients, SDS total r = 0.19 (n = 32 at week 10) and SF-36 r range - 0.20 to -0.01 (n = 51 at week 10, n = 183 at week 24). CONCLUSIONS: Atomoxetine-treated adult patients experienced improvements in functional outcomes (AAQoL and BRIEF-A Self-Report) that correlated with reductions in ADHD symptoms. Although atomoxetine improved both the ADHD symptoms and functional outcomes, the correlation between symptoms and functional outcomes was low to moderate, suggesting that they measure overlapping but different aspects of the disorder. Hence, clinicians should assess not just ADHD symptoms, but also the functional impairments.

Forgotten but not gone: new developments in the understanding and treatment of tardive dyskinesia.

The broad use of atypical antipsychotics was expected to dramatically reduce the prevalence and incidence of tardive dyskinesia (TD), but data show that TD remains an important challenge due the persistent nature of its symptoms and resistance to numerous treatment modalities, including antipsychotic discontinuation. Recent insights on genetic risk factors and new concepts surrounding pathophysiology have spurred interest in the possibility of targeted treatment for TD. As will be reviewed in this article, the number of evidence-based strategies for TD treatment is small: only clonazepam, amantadine, ginkgo biloba extract, and the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine have compelling data. Using new insights into the metabolism of tetrabenazine and the properties of its active metabolites, 2 modifications of tetrabenazine have been synthesized to improve the kinetic profile, and are currently involved in double-blind placebo controlled studies aimed at U.S. Food and Drug Administration (FDA) regulatory approval. The possible availability of these new agents, deuterated tetrabenazine and valbenazine, significantly widens the range of treatment choices for patients with TD. For clinicians with patients at risk for TD due to dopamine antagonist exposure, experience has shown that the problem of TD will be an ongoing issue in modern psychiatry, and that an appreciation of new developments in the pathophysiology of, risk factors for, and treatment of TD is crucial to managing this condition.

Effect of Atomoxetine on the Cognitive Functions in Treatment of Attention Deficit Hyperactivity Disorder in Children with Congenital Hypothyroidism: A Pilot Study.

BACKGROUND: With early initiation of thyroxine supplementation, children with congenital hypothyroidism (CH) retain some subtle deficits, such as attention and inhibitory control problems. This study assessed the effects of atomoxetine on cognitive functions in treatment of attention deficit hyperactivity disorder (ADHD) symptoms in children with CH. METHODS: In a 6-month, open-labeled pilot study, 12 children were recruited and received atomoxetine. The measures of efficacy were scores on the Swanson, Nolan and Pelham Teacher and Parent Rating Scale, version IV (SNAP-IV) and Clinical Global Impression-Severity scale (CGI-S). The cognitive functions were evaluated with the Wechsler Intelligence Scale for Chinese Children, Digit Span, Wisconsin Card Sorting Test, and Stroop test. RESULTS: A statistically significant difference was found between the mean CGI-S and SNAP-IV scores before and after treatment (p < 0.01). All the indicators of cognitive functions at the endpoint were improved compared with those at baseline. No serious adverse events were reported. CONCLUSION: Atomoxetine appears to be useful in improving ADHD symptoms, as well as cognitive functions, in children with CH. Larger, randomized, double-blinded, clinical trials are required to replicate these results.

Efficacy of atomoxetine for symptoms of attention-deficit/hyperactivity disorder in children with a history of child abuse.

OBJECTIVE: Recent studies suggest that the severity and drug response of depression and anxiety are correlated with childhood abuse. However, whether a history of child abuse can predict the severity and/or drug response of attention-deficit/hyperactivity disorder (ADHD) is unclear. Therefore, we conducted a retrospective study to assess the efficacy of atomoxetine in children with a history of child abuse. METHODS: We reviewed 41 cases of children treated with atomoxetine. Specifically, we compared dissociation associating symptoms (DAS) and other symptoms (OS) measured via the ADHD Rating Scale (ADHD-RS) in abused and nonabused children at baseline and at 8 weeks after atomoxetine administration. RESULTS: At baseline, abused children had higher total scores (38.7±9.3 vs. 30.5±9.4, p=0.011), and greater levels of hyperactivity/impulsivity (17.3±5.8 vs. 11.3±6.0, p=0.004) on the ADHD-RS than did nonabused children, whereas the inattention scores were similar between the two groups (21.4±4.8 vs. 19.2±4.6). Additionally, the total score and the two subscores decreased at week 8 for both groups. In the nonabused group, DAS (5.5±2.3 vs. 3.9±1.7, p<0.001) and OS (25.0±8.1 vs. 17.4±6.7, p<0.001) significantly decreased after atomoxetine treatment. However, DAS in the abused group did not change after atomoxetine treatment (5.9±2.3 vs. 5.1±1.8), whereas OS significantly decreased (32.8±7.6 vs. 25.7±7.2, p=0.002). CONCLUSIONS: If DAS were caused by traumatic experiences in abused children, trauma treatment tools other than pharmacotherapy might be useful to treat DAS. These tools may include eye movement desensitization and reprocessing and trauma-focused cognitive behavioral therapy.

Tardive dyskinesia (syndrome): Current concept and modern approaches to its management.

Tardive dyskinesia is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. The pathophysiology of tardive dyskinesia is complex, multifactorial and still not fully understood. A number of drugs were tried for the management of this motor disturbance, yet until now no effective and standard treatment has been found. It is very disappointing to realize that the introduction of antipsychotics from the second generation has not significantly decreased the prevalence and incidence of tardive dyskinesia. Therefore, the management of this motor disturbance remains an actual topic as well as a challenge for clinicians. This review summarizes recent relevant publications concerning the treatment of tardive dyskinesia.

[Conservative treatment in male urinary incontinence]. / Konservative Therapie der Harninkontinenz beim Mann.

Prevalence, pathophysiology, diagnostic and therapeutic approaches of urinary incontinence are well studied in women; however, studies on male urinary incontinence focus on incontinence following surgery of the bladder or prostate, predominantly incontinence after radical prostatectomy. Aging men suffer from incontinence, most frequently urge incontinence (overactive bladder, OAB), nearly as often as women do.The domain of conservative therapy of urinary stress incontinence in men is pelvic floor training. It remains unclear whether biofeedback procedures, electrostimulation therapy, or magnetic stimulation therapy can enhance pelvic floor training. There are data suggesting that an off-label therapy with Duloxetin®, a selective serotonin-noradrenaline reuptake inhibitor (SSNRI), improves urinary incontinence following radical prostatectomy. Antimuscarinic agents in combination with bladder training have been proven as safe and effective treatment in men with OAB. Data, however, suggest that men with OAB are far less frequently treated than women.

Antidepressant properties of aqueous macerate from Gladiolus dalenii corms.

BACKGROUND: Gladiolus dalenii Van Geel (Iridaceae) has been used for the treatment of depression and psychotic disorders in African traditional medicine. The aim of this study was to assess the effect of the aqueous extract from the corm of Gladiolus dalenii and its possible mechanisms of action. MATERIALS AND METHODS: We assessed the antidepressant properties of G. dalenii corm aqueous extract in mice, using the open field, forced swimming, and tail suspension tests. Spontaneous locomotor activity of mice given various doses of G. dalenii extract (per os) was determined in the open field, whereas immobility was evaluated in the other two tests. RESULTS: Extract maximal effect was observed at 15 mg/kg, as mice displayed a marked reduction in immobility time in both the forced swimming test (80%) and the tail suspension test (66%). In further studies aimed at investigating the mechanism of action of G. dalenii extract, the latter significantly antagonized the effect of N-methyl-D-aspartate (NMDA, 75 mg/kg) at both the doses 15 mg/kg (p<0.001) and 150 mg/kg (p=0.004). A significant reduction in immobility time was also observed following treatment with combinations of a sub-effective dose of extract (7.5 mg/kg) with either the NMDA receptor antagonist D-(-)-2-amino-7-phosphonoheptanoic acid (D-AP7, 50 mg/kg, P< 0.001), the serotonin reuptake inhibitor fluoxetine (5 and 10 mg/kg, P< 0.001 and P< 0.001 respectively), and the multi-target antidepressant imipramine (5 and 10 mg/kg, P< 0.001 and P< 0.001 respectively). Moreover, neither G. dalenii extract alone nor its combinations with NMDA ligands imipramine and fluoxetine enhanced mouse spontaneous locomotor activity. CONCLUSION: Altogether, these results suggest that G. dalenii has antidepressant properties, probably mediated through interactions with NMDA, serotonin and/ or noradrenergic systems, and may justify its use in traditional medicine.

Outcome of a standardized approach to childhood urinary symptoms-long-term follow-up of 720 patients.

AIMS: To investigate the relevance of enuresis subtyping for selection of treatment modality and for long-term outcome in a large consecutive patient cohort. MATERIALS AND METHODS: We included all patients referred for urinary incontinence during a 5-year period but excluding recurrent urinary tract infections (UTI). Type and severity of incontinence, prior history, results of examinations performed, number of visits, and effect of all treatments provided, were included in a clinical database. RESULTS: Seven hundred twenty children aged 4-16 years (mean 8.5 ± 2.2 years, 239 girls) were included in the analysis (42% with monosymptomatic (MNE), 55% with non-MNE, and 3% with isolated daytime incontinence). Initial evaluation revealed only few underlying causes (one neurological and eight anatomical). Investigations showed significant differences between MNE and non-MNE patients as both maximal voided volume and nocturnal urine volume was lower in non-MNE patients (P < 0.001). Follow-up for average 1,587 days (3.4 years) was performed in 660 (92%) patients. A higher number of visits and a longer treatment period were needed for non-MNE patients (on average 4.7 ± 2.8 visits) than MNE patients (3.1 ± 1.6 visits, P < 0.001). The most common treatment regimen that resulted in dryness in both MNE (40%) and non-MNE (36%) was the alarm system. Interestingly, of the 539 patients who initially were referred due to desmopressin resistance 177 (33%) of these were dry on desmopressin monotherapy. CONCLUSIONS: The study indicated that MNE and non-MNE are two distinct disease entities with different optimal treatments and showed that the latter patients are more difficult and time-consuming to manage.

A randomized placebo-controlled trial of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: A double-blind, randomized, placebo-controlled study was designed to assess the efficacy and safety of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD). The study started in August 2008 and ended in July 2012 and was conducted at Karakter Child and Adolescent Psychiatry University Centre in Nijmegen, The Netherlands. METHOD: Forty-one children (aged 8-15 years) with a DSM-IV-TR diagnosis of ADHD were randomly assigned to treatment with either EEG neurofeedback (n = 22) or placebo neurofeedback (n = 19) for 30 sessions, given as 2 sessions per week. The children were stratified by age, electrophysiologic state of arousal, and medication use. Everyone involved in the study, except the neurofeedback therapist and the principal investigator, was blinded to treatment assignment. The primary outcome was severity of ADHD symptoms on the ADHD Rating Scale IV, scored at baseline, during treatment, and at study end. Clinical improvement as measured by the Clinical Global Impressions-Improvement scale (CGI-I) was a secondary outcome. RESULTS: While total ADHD symptoms improved over time in both groups (F1,39 = 26.56, P < .001), there was no significant treatment effect, ie, group × time interaction (F1,39 = 0.36, P = .554); the same was true for clinical improvement as measured by the CGI-I (P = .092). No clinically relevant side effects were observed. Among the children and their parents, guessing treatment assignment was not better than chance level (P = .224 for children, P = .643 for parents). CONCLUSION: EEG neurofeedback was not superior to placebo neurofeedback in improving ADHD symptoms in children with ADHD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00723684.

Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis.

OBJECTIVES: To synthesise the available evidence on pharmacological and non-pharmacological interventions recommended for fibromyalgia syndrome (FMS). METHODS: Electronic databases including MEDLINE, PsycINFO, Scopus, the Cochrane Controlled Trials Registry and the Cochrane Library were searched for randomised controlled trials comparing any therapeutic approach as recommended in FMS guidelines (except complementary and alternative medicine) with control interventions in patients with FMS. Primary outcomes were pain and quality of life. Data extraction was done using standardised forms. RESULTS: 102 trials in 14 982 patients and eight active interventions (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors (SNRIs), the gamma-amino butyric acid analogue pregabalin, aerobic exercise, balneotherapy, cognitive behavioural therapy (CBT), multicomponent therapy) were included. Most of the trials were small and hampered by methodological quality, introducing heterogeneity and inconsistency in the network. When restricted to large trials with ≥100 patients per group, heterogeneity was low and benefits for SNRIs and pregabalin compared with placebo were statistically significant, but small and not clinically relevant. For non-pharmacological interventions, only one large trial of CBT was available. In medium-sized trials with ≥50 patients per group, multicomponent therapy showed small to moderate benefits over placebo, followed by aerobic exercise and CBT. CONCLUSIONS: Benefits of pharmacological treatments in FMS are of questionable clinical relevance and evidence for benefits of non-pharmacological interventions is limited. A combination of pregabalin or SNRIs as pharmacological interventions and multicomponent therapy, aerobic exercise and CBT as non-pharmacological interventions seems most promising for the management of FMS.

Cost effectiveness of guanfacine extended-release versus atomoxetine for the treatment of attention-deficit/hyperactivity disorder: application of a matching-adjusted indirect comparison.

BACKGROUND: About 7% of children and adolescents are diagnosed with attention-deficit/hyperactivity disorder (ADHD) in the US. Patients with ADHD who are intolerant of or do not have an optimal response to stimulants often use non-stimulants as alternative therapies. Guanfacine extended-release (GXR) and atomoxetine (ATX) are the only non-stimulants approved by the US Food and Drug Administration for once-daily use in the treatment of children and adolescents with ADHD in the US. ATX has been on the market since 2002 while GXR was recently approved in 2009. To date, there is no comparative effectiveness or cost-effectiveness study comparing the two drugs. OBJECTIVES: The aim of this study was to assess the cost effectiveness of GXR versus ATX for the treatment of ADHD in children and adolescents, using the comparative efficacy results from a matching-adjusted indirect comparison (MAIC). METHODS: The MAIC method was used to compare the efficacy between GXR (target dose and lower doses) and ATX (target dose) in the absence of head-to-head clinical trials. Individual patients in the GXR trials were weighted such that the summary baseline characteristics and the efficacy of the placebo arm of the GXR trials matched exactly with those from published ATX trials. After weighting, the efficacy (i.e. change in the ADHD rating scale, fourth edition [ADHD-RS-IV] total score from baseline) was compared between each GXR dosing group and the ATX group. The results from the MAIC analyses were used to populate a 1-year Markov model that is used to compare the cost effectiveness of GXR versus ATX from a US third-party payer perspective. Effectiveness outcomes for each treatment group were estimated as the proportion of responders, defined as patients with ≥25% reduction in ADHD-RS-IV total score from baseline, and average quality-adjusted life years (QALYs). Utilities associated with response/non-response and disutilities due to adverse events were applied in the model. Costs included drug and medical service costs and were inflated to 2011 US dollars ($US). Incremental cost/QALY and incremental cost/responder were estimated. Univariate sensitivity analyses were conducted by varying all model parameters, including costs, utilities, and response rate. RESULTS: The target dose of GXR was 0.12 mg/kg/day. In match-adjusted populations with balanced baseline characteristics, patients receiving GXR at the dose of 0.09-0.12(p = 0.0016) [DOSAGE ERROR CORRECTED] and 0.075-0.09 mg/kg/day (p = 0.0248) had better efficacy, while those receiving GXR at the dose of 0.046-0.075 mg/kg/day had comparable efficacy (p = 0.0699), compared with patients receiving ATX at the target dose of 1.2 mg/kg/day. In the base case of the cost-effectiveness analysis (CEA), GXR had incremental cost-effectiveness ratios of $US10 637/QALY and $US853/responder, compared with ATX (incremental costs: $US74; incremental effectiveness: 0.007 QALYs and 86 responders per 1000 patients treated). Results of all univariate sensitivity analyses showed that the model results were robust to changes in model inputs. CONCLUSIONS: To our knowledge, this is the first application of the novel comparative efficacy method of MAIC to a CEA model. The MAIC results indicate that GXR (0.075-0.12 mg/kg/day) was more effective than ATX (1.2 mg/kg/day) in the trial population. The CEA results indicate that GXR is cost effective compared with ATX for the treatment of ADHD in children and adolescents.

Sensory trick with metoclopramide-associated tardive tremor.

Tardive tremor is a 3-5 Hz bilateral resting and action tremor, associated with the use of dopamine receptor blocking drugs, accompanied by other tardive movement disorders and responsive to tetrabenazine or clozapine. We describe a case of a sensory trick associated with tardive tremor which raises important points about semiology and management. First, the presence of a sensory trick with tardive limb tremor suggests that the disorder may be a form of dystonia. Second, further study of osteopathic manipulative therapy for treatment of dystonia or tardive tremor is supported by a symptomatic response observed in our case.