The mixed amphetamine salt extended release (Adderall XR, Max-XR) as an adjunctive to SSRIS or SNRIS in the treatment of adult ADHD patients with comorbid partially responsive generalized anxiety: an open-label study

To examine the changes in partially responsive anxiety symptoms utilizing adjunctive treatment with the mixed amphetamine salt extended release (Adderall XR, MAX-XR) in the treatment of adult ADHD patients, with comorbid refractory anxiety. Consenting adult patients (n = 32) with confirmed diagnosis of generalized anxiety (GA) and comorbid (ADHD) participated in this open-label study. All patients had significant comorbid anxiety symptoms (HAM-A > 7) and failed to respond to 8-week trials of Serotonin Reuptake Inhibitors (SSRIs) or Norepinephrine Reuptake inhibitors (SNRIs). All patients were treated with the "Mixed Amphetamine salts Extended Release Adderall XR, (MAS-XR), as adjunctive to SSRIs or to SNRIs and were followed for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression severity subscale (CGI-S). Other scales included the Hamilton Anxiety Scale (HAM-A), the adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist, and Sheehan's disability scale. Baseline measures prior to the treatment with MAS-XR were compared to those at 4, 8, and at 12 weeks of treatment. Monitoring for pulse, blood pressure, and weight changes was carried out at baseline and at end point. All patients completed this open-label trial. There was significant and robust resolution of symptoms of all effectiveness measures, including the symptoms of anxiety, as shown by changes from baseline in HAM-A, ASRS-v1.1, and CGI at 8 weeks. Also there was significant reduction in the disability score at 12 weeks. Patients tolerated the treatment, and there were no significant cardiovascular changes at 12 weeks. There was decrease in mean weight at 12 weeks by 2.2 kg (P < .001). Mixed amphetamine salts MAS-XR can be used in adult patients with ADHD and comorbid anxiety symptoms. Larger controlled studies are needed to support the effectiveness of mixed amphetamine salts in patients with comorbid anxiety symptoms. Treatments need to include the targeting of the ADHD symptoms effectively in order to achieve better resolution of anxiety symptoms.     

Long-term open-label response to atomoxetine in adult ADHD: influence of sex, emotional dysregulation, and double-blind response to atomoxetine

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.     

Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients.     

Self-esteem in adolescent patients with attention-deficit/hyperactivity disorder during open-label atomoxetine treatment: psychometric evaluation of the Rosenberg Self-Esteem Scale and clinical findings

To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12–17 years), treated in an open-label study for 24 weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous structure of the SES could be confirmed. Reliability and internal consistency were moderate to excellent. Highest coefficients were found for the correlation between SES and GIPD scores. Self-esteem significantly increased over time, accompanied by an improvement of ADHD symptoms and related perceived difficulties. The Rosenberg SES was shown to be internally consistent, reliable, and sensitive to treatment-related changes of self-esteem. According to these findings, self-esteem may be an important individual patient outcome beyond the core symptoms of ADHD.     

Selective serotonin reuptake inhibitors,and serotonin and norepinephrine reuptake inhibitors for anxiety,obsessive-compulsive,and stress disorders: A 3-level network meta-analysis

BackgroundAnxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis.Methods and findingsWe searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies’ databases. No restriction was made regarding comorbidities with any other mental disorder, participants’ age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration’s risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD −0.56, 95% CI −0.62 to −0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials.ConclusionsIn this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy.

In a meta-analysis of randomized trials, Natan Pereira Gosmann and colleagues study efficacy of SSRIs and SNRIs for symptoms of anxiety, obsessive-compulsive, and stress-related disorders.     

Health-related quality of life in ADHD: a pooled analysis of gender differences in five atomoxetine trials

Attention-deficit/hyperactivity disorder (ADHD) is associated with considerable impairment in health-related quality of life (HR-QoL). Atomoxetine has been found to improve HR-QoL in both children and adolescents. However, there is scarcity of data on gender differences in treatment responses to ADHD medications. This pooled analysis of five atomoxetine trials aimed to evaluate treatment differences with respect to HR-QoL and ADHD symptoms across genders. Data from 5 clinical atomoxetine trials (4 from Europe and 1 from Canada) with similar inclusion and exclusion criteria and similar durations (8- to 12-week follow-up) were included in the pooled analysis. All studies included the Child Health and Illness Profile-Child Edition (CHIP-CE) Parent Report Form. In addition, correlations between HR-QoL and ADHD core symptoms were compared between girls and boys. Data from 136 girls and 658 boys (mean age: 9.6 and 9.7 years, respectively) were pooled. Boys and girls were similarly impaired at baseline with minor differences in some of the subdomains. Treatment effect of atomoxetine was significant in both groups for the Risk Avoidance domain and its subdomains. No gender effect with both clinical and statistical significance was found for treatment outcome. Correlations between ADHD Rating Scale and CHIP-CE scores were similar in both genders and were generally low at baseline and moderate at endpoint and for the change from baseline to endpoint. Atomoxetine was effective in improving some aspects of HR-QoL in both genders without any significant differences across genders. Correlations between core symptoms of ADHD and HR-QoL were low to moderate in both boys and girls.     

Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD

Few studies have examined the impact of childhood attention deficit hyperactivity disorder (ADHD) symptoms on adult ADHD functional outcomes. To address this issue dimensionally, ADHD symptoms in childhood and adulthood and their relation to educational deficits and work disability are studied in a clinical sample of adult patients with previously untreated ADHD. About 250 adults diagnosed systematically with ADHD according to DSM-IV were prospectively recruited. Primary outcomes were high school dropout and being out of the work last year. Childhood ADHD symptoms, sex differences, comorbidities of other mental disorders, and adult ADHD symptoms were examined by historical data, clinician interviews, and questionnaires. High levels of ADHD symptom severity in childhood were related to dropping out of high school [odds ratio (OR) = 3.0], as were higher numbers of hyperactive–impulsive symptoms in childhood. Significantly, more women than men were long-term work disabled (OR = 2.0). After adjusting for age and gender, persisting high levels of ADHD inattention symptoms in adulthood (OR = 2.5), number of comorbid disorders, and particularly anxiety disorders were significantly related to long-term work disability. Childhood hyperactive–impulsive symptoms and overall severity of childhood ADHD symptoms were associated with high school dropout rates; however, persisting ADHD inattention symptoms and comorbid mental disorders in adulthood were more correlated to occupational impairment. These findings underline proposals for studies on early recognition and interventions for ADHD and psychiatric comorbidity. They further suggest that inattentive symptoms be a focus of adult ADHD treatment and that workplace interventions be considered to prevent long-term work disability.     

Epilepsy Associated Depression: An Update on Current Scenario,Suggested Mechanisms,and Opportunities

Depression is one of the most frequent psychiatric comorbidities associated with epilepsy having a major impact on the patient’s quality of life. Several screening tools are available to identify and follow up psychiatric disorders in epilepsy. Out of various psychiatric disorders, people with epilepsy (PWE) are at greater risk of developing depression. This bidirectional relationship further hinders pharmacotherapy of comorbid depression in PWE as some antiepileptic drugs (AEDs) worsen associated depression and coadministration of existing antidepressants (ADs) to alleviate comorbid depression has been reported to worsen seizures. Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) are first choice of ADs and are considered safe in PWE, but there are no high-quality evidences. Similar to observations in people with depression, PWE also showed pharmacoresistant to available SSRI/SNRIs, which further complicates the disease prognosis. Randomized double-blind placebo-controlled clinical trials are necessary to report efficacy and safety of available ADs in PWE. We should also move beyond ADs, and therefore, we reviewed common pathological mechanisms such as neuroinflammation, dysregulated hypothalamus pituitary adrenal (HPA) axis, altered neurogenesis, and altered tryptophan metabolism responsible for coexistent relationship of epilepsy and depression. Based on these common pertinent pathways involved in the genesis of epilepsy and depression, we suggested novel targets and therapeutic approaches for safe management of comorbid depression in epilepsy.

     

ADHD in acute care psychiatric inpatients

Attention-deficit hyperactivity disorder (ADHD) is a neurocognitive disorder characterized by symptoms of inattention, impulsivity and motor hyperactivity. The worldwide prevalence of ADHD, in the general adult population, has been estimated to be 2.8%. Patients with ADHD have a high incidence of comorbidity with other psychiatric disorders. Those with a psychiatric disorder as well as ADHD have more psychosocial difficulties than those without ADHD. Despite knowing that ADHD is often comorbid with other psychiatric diagnoses, there are currently no studies elucidating the prevalence of ADHD in the inpatient psychiatric population, nor is there significant information about its impact. The lack of research into this topic suggests more needs to be done in the field of adult ADHD, especially in the inpatient psychiatric population and with respect to impairment in patient function. Knowing the prevalence of ADHD and its impact on quality of life in adult inpatients will help lay the groundwork for effective screening and management. The purpose of this study was to understand the prevalence rates of ADHD among psychiatric acute care inpatients. Other objectives included comparing the quality of life and functioning between patients with a primary psychiatric diagnosis and ADHD (treated or untreated) versus those with a primary psychiatric diagnosis and no ADHD. Thirty-three (N = 31) psychiatric inpatients were screened using the Adult ADHD Self-Report Scale. Those that screened positive for ADHD received a full diagnostic assessment for ADHD. All patients completed the Weiss Functional Impairment Rating Scale (WFIRS) to assess level of functioning and a Clinical Global Impression of Severity/Improvement Scale (on admission and discharge). Demographic information was also obtained. Of the 31 patients analyzed, 12 had a diagnosis of ADHD (36.4%). The participants diagnosed with ADHD scored significantly higher on the WFIRS, suggesting decreased functioning compared to patients without comorbid ADHD. Patients with ADHD also scored significantly higher in the individual domains of this rating scale, suggesting impairment in family, work and social functioning as well as decreased life-skills, poor self-concept and increased risk-taking behavior. In this sample, the prevalence of ADHD is significantly higher among acute care psychiatric inpatients than in the general population. Patients with concomitant ADHD suffer more functional impairment than those without. These findings merit further investigation into the value of routine screening and patient-specific treatment of ADHD in this patient population.     

Atomoxetine response in the inattentive and combined subtypes of attention deficit hyperactivity disorder: a retrospective chart review

The DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 1994, American Psychiatric Association) describes attention deficit hyperactivity disorder (ADHD) as a heterogeneous disorder; providing diagnostic criteria for three subtypes: hyperactive/impulsive (ADHD/HI), inattentive (ADHD/I), and combined type (ADHD/C). Differences among the subtypes are well defined, but there may be also differences in terms of treatment responses. The aim of this study is to assess the responses of ADHD/I and ADHD/C to atomoxetine treatment. The medical records of the January–June 2012 term, first time referrals to outpatient clinic, were reviewed, and 37 ADHD diagnosed primary school age children (18 ADHD/I, 19 ADHD/C) that were treated with atomoxetine were determined. Thirty-five of them who completed 8 weeks of treatment duration were recruited for the study. The children with an ADHD medication use history in 2 months time prior to onset of treatment and/or the children receiving additional psychopharmacologic treatment to atomoxetine were excluded. Baseline and eighth week assessment, records were evaluated. Efficacy assessments included Turgay DSM-IV ADHD Screening and Rating Scale parent and teacher forms (T-DSM-IV) and Clinical Global Impression Scale-Severity and Improvement subscales. Safety assessments included laboratory and body weight assessments, ECG, heart rate, and blood pressure evaluations (baseline and eighth week) along a scale filled by the parents at the eighth week to review side effects. Atomoxetine was found to be effective in both ADHD/I and ADHD/C groups. Atomoxetine also decreased the opposition defiance subscale scores of T-DSM-IV (both parent and teacher forms), whereas it was not found to make statistically significant difference in the conduct disorder subscale scores. Mean difference in 8-week time in T-DSM-IV hyperactivity subscale and total scores of parent and teacher forms; inattention subscale scores of only parent forms and the CGI- severity subscale scores; differed significantly among the ADHD/I and ADHD/C groups; that ADHD/C types responded better to medication. Results of this study revealed that atomoxetine is effective both in ADHD/I and ADHD/C subtypes. ADHD/C types may be responding better to atomoxetine treatment than the ADHD/I subtypes.     

Comorbidity and continuity of attention deficit hyperactivity disorder (ADHD) from childhood to adolescence in Turkey

The aim of this study was to examine clinical outcomes, psychiatric comorbidity and neuropsychological characteristics in Turkish adolescents with an attention deficit hyperactivity disorder (ADHD) diagnosis in childhood. A total of 45 children with ADHD diagnosis and 28 children with a psychiatric diagnosis other than ADHD in a 1-year cohort of 7–10-year-olds were reevaluated 6 years later using Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime version and Wechsler Intelligence Scale for Children-Revised and Stroop Test TBAG version. This study shows that the clinical outcomes and the comorbidity patterns for ADHD from childhood to adolescence in Turkey are similar to reported rates in the Western countries. In the ADHD group, 75.6 % still has impairing ADHD symptoms and 46.6 % has comorbid psychiatric disorders. The main difference is anxiety disorders being the most common comorbid disorders (37.8 %) in Turkish ADHD youth. These findings stress the high comorbidity associated with ADHD and support the importance of assessment and treatment for ADHD and comorbidities during adolescence.     

Comparative Efficacy and Acceptability of Antidepressants in Parkinson's Disease: A Network Meta-Analysis

Background

Depression is a common non-motor symptom in patients with Parkinson''s disease (PD). There are many kinds of antidepressants being used, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and Dopamine agonists which are suggested as alternative antidepressants for the treatment of depression in PD. Which one should we choose first? Literatures have shown inconsistent results.

Methods

We conducted a network meta-analysis of randomized controlled trials to compare the efficacy and acceptability of therapeutic methods for the treatment of depression in Parkinson''s disease.

Results

We used the odds ratios (OR) as effect size firstly and the results indicated no statistical significance between each compared intervention. Then we used the logarithm of the individual odds ratios as effect size. With efficacy of TCAs as the standard of comparison, the degree of incoherence (a measure of how closely the entire network fits together) was small (ω =  4.824827e-05). The logor were: SSRIs −0.69 (95% CI −1.28– −0.10); Pramipexole −0.73 (−1.71– −0.26); Pergolide −1.97 (−3.67– 0.27); SNRIs −0.86 (−1.86– 0.15); Placebo −1.24 (−1.99– −0.50). With Placebo as the standard of comparison, the logor were: TCAs 1.24 (0.50– 1.99); SSRIs 0.55 (−0.03– 1.13); Pramipexole 0.51 (−0.12– 1.15); Pergolide −0.73 (−2.25– 0.80); SNRIs 0.38 (−0.42– 1.19); TCAs, pramipexole, pergolide and SNRIs showed better profile of acceptability, leading to significant fewer discontinuations than that of SSRIs.

Conclusions

There is insufficient evidence to support antidepressant efficacy for SSRIs, pramipexole, pergolide and SNRIs. TCAs might be the best choice when starting antidepressant treatment in patients of Parkinson''s disease because it has the most favorable balance between benefits and acceptability, followed by pramipexole and SNRIs, SSRIs might be the last choice.     

Assessment of effects of atomoxetine in adult patients with ADHD: consistency among three geographic regions in a response maintenance study

A previous study (Upadhyaya et al. in Eur J Psychiatry 2013b; 27:185–205) reported that adults with attention-deficit/hyperactivity disorder (ADHD) demonstrated maintenance of response for up to 25 weeks after initially responding to atomoxetine treatment. In the present report, the consistency of treatment effect across three geographic regions (Europe, United States/Canada [US/Can], and Latin America [Latin Am]) was explored. Data were analyzed from a phase 3, multicenter, randomized, double-blind, maintenance-of-response (randomized withdrawal) trial of atomoxetine versus placebo in adults with ADHD. Patients were randomized to atomoxetine (N = 266) or placebo (N = 258) for 25 weeks. Consistency assessments included the interaction test, pairwise t tests, noninferiority, and the criteria from Basic Principles on Global Clinical Trials (Ministry of Health, Labour and Welfare of Japan 2007). Atomoxetine-treated patients maintained the improved ADHD symptoms relative to placebo-treated patients on the Conners’ Adult ADHD Rating Scale Investigator-Rated: Screening Version 18-Item (CAARS-Inv:SV) total score in all three regions (atomoxetine–placebo mean difference = ?4.55, ?3.18, and ?0.07 for Europe, US/Can, and Latin Am, respectively). For the Latin Am region, the mean change in total score (0.41) was notably smaller for the placebo group than for Europe (5.87) and US/Can (4.39). Similar results were observed for the CAARS-Inv:SV hyperactivity/impulsivity and inattention subscale scores. Overall, patients maintained the response with atomoxetine treatment compared to placebo; however, the magnitude of treatment effect differed among the regions studied, being numerically higher in the EU and US/Can than Latin Am. Trial registration http://www.clinicaltrials.gov/(NCT00700427).     

Evaluation of the efficacy and effectiveness of a structured disorder tailored psychotherapy in ADHD in adults: study protocol of a randomized controlled multicentre trial

ADHD is a serious risk factor for co-occurring psychiatric disorders and negative psychosocial consequences in adulthood. Previous trials on psychotherapeutic concepts for adult ADHD are based on behavioural (cognitive behavioural and dialectical behavioural) psychotherapeutic approaches and showed significant effects. The aim of our study group (COMPAS) is to carry out a first randomized and controlled multicentre study to evaluate the effects of a disorder tailored psychotherapy in adult ADHD compared to clinical management in combination with psychopharmacological treatment or placebo. A total of 448 adults with ADHD according to DSM-IV will be treated at seven university sites in Germany. In a four-arm design, patients are randomized to a manualized dialectical behavioural therapy (DBT) based group programme plus methylphenidate or placebo or clinical management plus methylphenidate or placebo with weekly sessions in the first 12 weeks and monthly sessions thereafter. Therapists are graduated psychologists or physicians. Treatment integrity is established by independent supervision. Primary endpoint (ADHD symptoms measured by the Conners Adult Rating Scale) is rated by interviewers blind to the treatment allocation. Intention-to-treat analysis will be performed within a linear regression model (Current Controlled Trials ISRCTN54096201). The trial is funded by the German Federal Ministry of Research and Education (01GV0606) and is part of the German network for the treatment of ADHD in children and adults (ADHD-NET).     

Predictors of relapse or maintenance of response in pediatric and adult patients with attention-deficit/hyperactivity disorder following discontinuation of long-term treatment with atomoxetine

We identified relapse/maintenance-of-response (MOR) predictors following discontinuation of long-term atomoxetine treatment in pediatric and adult patients with attention-deficit/hyperactivity disorder (ADHD) and assessed correlations between ADHD symptoms and quality of life (QoL). Post hoc analyses of data from two randomized, double-blind, placebo-controlled, phase 3 withdrawal studies in patients with ADHD meeting predefined response criteria before randomization. Study 1: patients (N = 163; 6–15 years) received atomoxetine (1.2–1.8 mg/kg/day) for 1 year, followed by randomization to atomoxetine (n = 81) or placebo (n = 82) for 6 months. Study 2: patients (N = 524; 18–50 years) received atomoxetine (80–100 mg/day) for ~6 months, followed by randomization to atomoxetine (n = 266) or placebo (n = 258) for ~6 months. Placebo patients were used for the analyses. Relapse: ≥50% worsening of prerandomization improvement in ADHD symptoms and ≥2 level severity increase on the Clinical Global Impression-Severity (CGI-S) scale at 2 consecutive visits; MOR: retaining ≥75% of prerandomization symptom improvement and CGI-S ≤ 2 at all visits (study 1); retaining ≥70% of prerandomization symptom improvement and CGI-S ≤ 3 at all visits (study 2). In adults, statistically significantly (P ≤ .05) increased likelihood of relapse was associated with prerandomization presence of Conners’ Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator-Rated:Screening Version (CAARS-Inv:SV) items “difficulty awaiting turn” and “careless mistakes.” In pediatric patients, less MOR was associated with prerandomization presence of ADHD Rating Scale-IV-Parent Version Investigator-Rated item “does not listen”; in adults, less MOR was associated with prerandomization presence of CAARS-Inv:SV items “loses things” and “difficulty awaiting turn.” Changes in patients’ QoL after withdrawal from atomoxetine moderately correlated with changes in ADHD symptoms in pediatric patients and mildly in adults.     

Prevalence of comorbid substance use disorder during long-term central stimulant treatment in adult ADHD

Central stimulant (CS) therapy is a cornerstone in treatment of adult attention-deficit/hyperactivity disorder (ADHD). Substance use disorder (SUD) is a common comorbid disorder of ADHD and might complicate the treatment. Our main objectives were to investigate the prevalence of SUD during CS treatment, and identify variables associated with SUD during the treatment. The collection of data was based on a naturalistic, retrospective approach using the medical records of a cohort of all adult ADHD patients (N = 117) starting treatment with CS in a specific catchment area in the period 1997 to May 2005. A logistic regression model was applied to identify possible predictors of SUD during CS treatment. The study showed no onset of SUD during the CS treatment in the group of patients without comorbid SUD at baseline (mean CS treatment length 41.1 months). In the group of patients with comorbid SUD at baseline, 58.5 % had one or more relapses of SUD during treatment (mean CS treatment length 27.9 months). Younger age and comorbid antisocial personality disorder were associated with relapse. In a logistic regression analysis, cannabis abstinence for more than 12 months was a negative predictor for relapse of SUD. CS treatment does not precipitate onset of SUD in adults without previous SUD.     

Obsessive–compulsive adults with and without childhood ADHD symptoms

Obsessive–compulsive disorder (OCD) and attention-deficit and hyperactivity disorder (ADHD) frequently coexist. To understand whether childhood ADHD can increase the risk of OCD in adulthood and whether it influences the phenomenology of OCD, we investigated the symptoms of ADHD during childhood in obsessive–compulsive adults who had never been diagnosed as ADHD. Adults with OCD (n = 83) were given the Wender Utah Rating Scale (WURS), Yale–Brown Obsessive Compulsive Scale (Y-BOCS), Barratt Impulsiveness Scale-11 (BIS-11), Hamilton Depression Rating Scale-17 (HDRS-17) and Beck Anxiety Inventory (BAI). The prevalence of childhood ADHD symptoms was 40.9 % (n = 34) and that of adult ADHD was 16.9 % (n = 14). Patients with childhood ADHD symptoms had an earlier onset of OCD, higher scores of the BAI and BIS-11. The scores of the Y-BOCS and HDRS-17 did not differ between those having and not having childhood ADHD symptoms. Childhood history of ADHD symptoms is common in adult OCD patients who have never been diagnosed as ADHD. Childhood ADHD symptoms are associated with an earlier age of OCD, more severe anxiety and higher impulsiveness. Even remitted ADHD may be a risk factor for OCD in later life.     

Effects of Milnacipran in Animal Models of Anxiety and Memory

Serotonin (5-HT) and noradrenaline (NA) are involved in both pathogenesis and recovery from depression and anxiety. We examined the effects of acute and chronic treatment with milnacipran, a serotonin/noradrenaline reuptake inhibitors (SNRIs) antidepressant, on anxiety and memory retention in rats. Male Wistar rats received acute or chronic administration of milnacipran (12.5, 25 or 50 mg/kg) or saline (control group). The animals were separately submitted to elevated plus-maze, inhibitory avoidance and open-field tasks 1 h after injection, in the acute group, or 23 h after last injection, in the chronic group. Our results showed an anxiolytic-like effect after chronic administration of milnacipran at doses of 25 and 50 mg/kg. The treatment does not interfere in memory retention and habituation to a novel environment at any doses studied. These findings support that milnacipran, an established SNRIs antidepressant, can also be useful in the treatment of anxiety disorders.     

Treatment compliance or medication adherence in children and adolescents on ADHD medication in clinical practice: results from the COMPLY observational study

Although the efficacy and tolerability of ADHD medications have been investigated fairly extensively, there are very few data comparing the different types of medication (e.g. psychostimulants, non-stimulants) in terms of medication adherence. The primary research objective of the COMPLY observational study was to evaluate medication adherence (i.e. compliance) over 1 year in children and adolescents with ADHD in a routine clinical setting. COMPLY was a prospective 12-month, observational, open-label study that included children and adolescents, aged 6–17 years, with ADHD. Medication adherence (i.e. compliance) was measured using the Pediatric Compliance Self-Rating (PCSR) instrument and using items 1–4 of the Medication Adherence Rating Scale (MARS). A total of 504 patients were enrolled. At baseline, 252 patients (50.0 %) were prescribed non-stimulant (atomoxetine) medication and 247 patients (49.0 %) were prescribed psychostimulant medication. Both types of medication were prescribed concomitantly in five patients (1.0 %). After 12 months, 123 patients (48.8 %) were taking atomoxetine and 176 patients (71.3 %) were taking psychostimulants. Adherence (PCSR score ≥5) was present in both groups (atomoxetine: 67.5 %; psychostimulant: 74.2 %) throughout the observation period. MARS scores declined over time in both groups (atomoxetine: from 3.7 to 2.9; psychostimulant: from 3.6 to 3.1), indicating a deterioration in adherence. There was no statistically significant difference in terms of medication adherence between the two groups.     

Traitement psychopharmacologique du trouble obsessionnel compulsif de l’enfant et de l’adolescent

The present report review available literature on psychopharmacological treatment of obsessive compulsive disorder (OCD) in children and adolescents. There is now clear evidence that drugs that are potent serotonin reuptake inhibitors (clomipramine and SSRIs) induce a clinically substantial reduction of OC symptoms for most children and adolescents with the disorder. However, improvement is often incomplete, few patients become asymptomatic, and long-term maintenance treatment may be required. Cognitive behavioural treatment, based on graded exposure with response prevention, might have more durable benefits, and is considered as the first line treatment in mild non comorbid OCD. Because OCD frequently occurs in the context of other psychopathology and adaptative difficulties, additional individual and family psychotherapy, pharmacological associations and educational interventions are often necessary.