A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients.

The lack of head-to-head clinical studies powered to compare atomoxetine and osmotic release oral system (OROS) methylphenidate necessitates treatment comparison by methods that include indirect evidence such as network meta-analysis (NMA). A NMA assessing the relative treatment effects of atomoxetine and OROS methylphenidate in adults with attention-deficit/hyperactivity disorder (ADHD) was conducted. Studies were identified by systematic literature review. Analyses summarised improvements in efficacy, measured by ADHD-specific scales, using Cohen'sdto calculate the standardised mean difference (SMD), and all cause discontinuations. Results showed effect sizes (SMD, 95% credible interval (CrI)) relative to placebo that did not differ significantly between atomoxetine (0.46, 0.36-0.56) and OROS methylphenidate (0.51, 0.40-0.63) in clinical studies of up to 12 weeks' duration (SMD, 95% CrI for atomoxetine versus OROS methylphenidate: -0.05, -0.18-0.08). Patients treated with these medications responded better than those given placebo across all analyses. There was also no significant difference in discontinuation rates between atomoxetine and OROS methylphenidate (odds ratio, 95% CrI: 0.85, 0.53-1.35). Between-study heterogeneity was low overall. Results of this NMA suggest that the efficacy of atomoxetine and OROS methylphenidate in adults does not differ significantly. Clinical guidelines may require amendment to reflect these recent data.

Understanding the treatment of attention deficit hyperactivity disorder in newly diagnosed adult patients in general practice: a UK database study.

BACKGROUND: Adult attention deficit hyperactivity disorder (ADHD) has been largely ignored in psychiatric and general practice guidance until recently. Adult ADHD has a high social and medical burden, but health care is not well described in the UK. The main study objective was to evaluate a primary care adult ADHD population in terms of prescribing and health care contact rates. METHODS: This was a retrospective observational study using data from the Clinical Practice Research Database from January 1, 2002 to July 31, 2011. Adult patients with an incident ADHD diagnosis or ADHD medication were identified as having been free of ADHD medication or diagnoses in the previous 2 years. Patients were followed for 12-24 months after diagnosis. RESULTS: Of the 663 patients with ADHD in the cohort, 54.1% were prescribed ADHD medication during the observation period. During the first 6 months, 34.2% of patients initiated methylphenidates and 14.0% atomoxetine. In total, 36.3% patients were referred to secondary care psychiatry during observation, with the remaining population (63.7%) never having a referral. Most of the referrals were before diagnosis in primary care. At the end of the observation period, 16.2% of patients were on antipsychotics, 17.3% hypnotics, and 34.8% antidepressants or anxiolytics; however, some patients appeared to be prescribed antipsychotic or antidepressant medications even if they did not have an observable diagnosis in their records. Health care contact rates (general practitioner or hospital) increased by 39.2% post-diagnosis (incidence rate ratio: 1.39; 95% confidence interval: 1.32, 1.47), which may be related to the need for medication monitoring and titration. CONCLUSION: This study has shown in primary care that there is relatively low use of ADHD medication, low referrals into secondary care, high rates of usage of psychiatric non-ADHD medications for different indications, and an increasing burden in terms of health care contacts in adult ADHD patients post-diagnosis.

Health state utilities associated with adult attention-deficit/hyperactivity disorder.

OBJECTIVES: With growing awareness of the importance of adult attention-deficit/hyperactivity disorder (ADHD) treatment, cost-effectiveness analyses, including utilities, are needed to compare the value of treatment options. Although utilities have been reported for childhood ADHD, little is known about utilities representing adult ADHD. Therefore, the purpose of this study was to estimate utilities associated with adult ADHD. METHODS: Health-state descriptions of adult ADHD were drafted based on literature review, interviews with four clinicians, and clinical trial data. Health states were revised based on a pilot study with 26 participants. Final health states were rated in time trade-off interviews with general population respondents in London and Edinburgh, UK. RESULTS: A total of 158 participants completed interviews (mean age =47.0 years; 49.4% female; Edinburgh =80 participants). Mean (standard deviation [SD]) utilities were 0.82 (0.17), 0.68 (0.28), and 0.67 (0.28) for health states describing treatment responders (health state A), nonresponders (health state B), and untreated patients (health state C), respectively. Most participants rated health state A as preferable to B (n=92; 58.2%) and C (n=97; 61.4%). The majority rated B and C as equal (n=125; 79.1%). Paired Student's t-tests found that A had a significantly greater mean utility than B (t=10.0; P<0.0001) and C (t=10.2; P<0.0001). CONCLUSION: The current study provides utilities that may be used in cost-utility models of treatment for adult ADHD. Results reflected clear differences between health states representing treatment responders and nonresponders/untreated patients. Current utilities were comparable to those previously reported for childhood ADHD.

Impact of pretreatment with antidepressants on the efficacy of duloxetine in terms of mood symptoms and functioning: an analysis of 15 pooled major depressive disorder studies.

OBJECTIVE: This post hoc analysis aimed to determine whether patients with major depressive disorder (MDD) in duloxetine trials who were antidepressant naive or who were previously exposed to antidepressants exhibited differences in efficacy and functioning. METHOD: Data were pooled from 15 double-blind, placebo- and/or active-controlled duloxetine trials of adult patients with MDD conducted by Eli Lilly and Company. The individual studies took place between March 2000 and November 2009. Data were analyzed using 4 pretreatment subgroups: first-episode never treated, multiple-episode never treated, treated previously only with selective serotonin reuptake inhibitors (SSRIs), and previously treated with antidepressants other than just SSRIs. Measures included the 17-item Hamilton Depression Rating Scale (HDRS-17) total and somatic symptom subscale scores, Montgomery-Asberg Depression Rating Scale (MADRS) total score, and Sheehan Disability Scale total score. Response rates (50% and 30%) were based on the HDRS-17 total score and remission rates on either the HDRS-17 or MADRS total score. RESULTS: Response and remission rates were significantly greater (P < .05 in 11 of 12 comparisons) for duloxetine versus placebo in the 4 subgroups. A trend of greater response and remission occurred for first-episode versus multiple-episode patients; both groups were generally higher than the antidepressant-treated groups. Mean changes in efficacy measures were mostly significantly greater (P < .05 in 13 of 16 comparisons) for duloxetine versus placebo within each pretreatment subgroup, with some (P < .05 in 2 of 24 comparisons) significant interaction effects between subgroups on HDRS-17 total and somatic symptoms scores. CONCLUSIONS: Duloxetine was generally superior to placebo on response and remission rates and in mean change on efficacy measures. Response and remission rates were numerically greater for first-episode versus multiple-episode and drug-treated patients. Mean change differences on efficacy measures among the 4 subgroups were inconsistent. Duloxetine showed a similar therapeutic effect independent of episode frequency and antidepressant pretreatment.