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.

A review of the efficacy of atomoxetine in the treatment of attention-deficit hyperactivity disorder in children and adult patients with common comorbidities.

Attention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that is often diagnosed during childhood, but has also increasingly been recognized to occur in adults. Importantly, up to 52% of children (including adolescents) and 87% of adults with ADHD also have a comorbid psychiatric disorder. The presence of a comorbid disorder has the potential to impact diagnosis and could affect treatment outcomes. Atomoxetine is a nonstimulant treatment for ADHD. Despite numerous published studies regarding efficacy of atomoxetine in the treatment of ADHD in patients with comorbid disorders, there is limited information about the impact of individual common comorbid disorders on the efficacy of atomoxetine for ADHD, especially with regard to adults. Moreover, a cumulative review and assessment of these studies has not been conducted. For this reason, we performed a literature review to find, identify, and cumulatively review clinical studies that examined the efficacy of atomoxetine in the treatment of patients with ADHD and comorbid psychiatric disorders. We found a total of 50 clinical studies (37 in children; 13 in adults) that examined the efficacy of atomoxetine in patients with ADHD and a comorbid disorder. The comorbidities that were studied in children or in adults included anxiety, depression, and substance use disorder. Overall, the presence of comorbidity did not adversely impact the efficacy of atomoxetine in treatment of ADHD symptoms in both patient populations. In the studies identified and assessed in this review, atomoxetine did not appear to exacerbate any of the comorbid conditions and could, therefore, be an important therapy choice for the treatment of ADHD in the presence of comorbid disorders.

Burden of illness and health care resource utilization in adult psychiatric outpatients with attention-deficit/hyperactivity disorder in Europe.

OBJECTIVE: To assess the burden of illness and health care resource utilization of adult nonpsychotic psychiatric outpatients with attention-deficit/hyperactivity disorder (ADHD) in Europe. METHODS: This was a multicountry, cross-sectional, observational study where unselected routine patients from clinical psychiatric outpatient settings were screened and assessed for ADHD. Patients were evaluated using the Clinical Global Impressions of Severity (CGI-S) scale, the Sheehan Disability Scale (SDS), and the EuroQol-5 Dimensions questionnaire. Data on comorbidities, functional impairment, and health care resource utilization were captured. RESULTS: The study enrolled 2284 patients, of whom 1986 completed the study. The prevalence of ADHD was 17.4%, of whom 46.0% had a previous ADHD diagnosis. Patients with ADHD had a high clinical burden with psychiatric comorbidities, especially depression (43.0%) and anxiety disorders (36.4%). Substance abuse (9.2% vs. 3.4%) and alcohol abuse (10.3% vs. 5.2%) were more common in the ADHD cohort vs. the non-ADHD cohort. Only 11.5% of the patients with ADHD had no other psychiatric disorder. Various measures indicated a significantly poorer level of functioning for patients with ADHD than without ADHD, as indicated by higher scores for CGI-S (3.8 vs. 3.3) and SDS (18.9 vs. 11.6) and higher percentages of debt (35.5% vs. 24.3%) and criminality (13.8% vs. 6.1%). Lastly, the health care resource utilization was considerable and similar between adult psychiatric outpatients diagnosed and not diagnosed with ADHD. CONCLUSIONS: Although care was taken when choosing the sites for this study, to make it representative of the general outpatient adult psychiatric population, caution should be advised in generalizing the findings of our study to the general ADHD or psychiatric outpatient population. This was an observational study, thus no inference on causality can be drawn. Having ADHD imposes a considerable health and social burden on patient and health care resource utilization comparable to other chronic psychiatric disorders.

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.

Post Hoc Analysis of Potential Predictors of Response to Atomoxetine for the Treatment of Adults with Attention-Deficit/Hyperactivity Disorder using an Integrated Database.

BACKGROUND: Responses to atomoxetine vary for individual patients with attention-deficit/hyperactivity disorder (ADHD). However, we do not know whether any factors can be used to reliably predict how individuals with ADHD will respond to treatment. OBJECTIVE: Our objective was to evaluate background variables that facilitate early identification of those adults with ADHD who are likely to respond to treatment with atomoxetine. METHODS: We pooled data for atomoxetine-treated adults with ADHD from 12 clinical trials for a short-term (10-week) analysis, and from 11 clinical trials for a long-term (24-week) analysis. Patients not meeting a response definition [≥30 % reduction in Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version (CAARS-Inv:SV) total score and Clinical Global Impressions of ADHD Severity Scale (CGI-S) score ≤3 at endpoint], or who discontinued, were defined as non-responders. Another definition of response (≥30 % reduction in CAARS-Inv:SV total score at endpoint) was also used in these analyses; only the results with the former definition are shown in this abstract, as the same conclusions were gained with both definitions. A treatment-specified subgroup detection tool (a resampling-based ensemble tree method) was used to identify predictors of response. RESULTS: Of 1945 adults in the long-term analysis, 548 (28.2 %) were responders to atomoxetine at week 24; 65.2 % of 1397 non-responders had discontinued. Of 4524 adults in the short-term analysis, 1490 (32.9 %) were responders at week 10; 33.2 % of 1006 non-responders had discontinued. No analyzed baseline parameters (age, sex, prior stimulant use, ADHD subtype, CAARS-Inv:SV, CGI-S) were statistically significant predictors of response. Reductions in CAARS-Inv:SV total, CAARS-Inv:SV subscores, and CGI-S at week 4 in the short-term analysis, and at weeks 4 or 10 in the long-term analysis, were statistically significant predictors of response, i.e., patients with versus without these reductions early in treatment were more likely to be clinical responders at later time points. Sensitivity ranged from 28.6 to 85.9 %, and specificity ranged from 23.8 to 86.7 %. Predictors with higher sensitivity had lower specificity, and vice versa. CONCLUSIONS: Reductions in CAARS-Inv:SV and CGI-S scores at weeks 4 and 10 are statistically significant predictors of response to atomoxetine at later time points in adults with ADHD. However, the predictors identified by these analyses are not reliable enough for use in clinical practice. The only currently available method to judge whether individuals with ADHD will respond to atomoxetine is to start treatment and assess the response over an extended period, sometimes longer than 10 weeks.

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.

Atomoxetine in patients with ADHD: A clinical and pharmacological review of the onset, trajectory, duration of response and implications for patients.

This article reviews data providing new insight into the trajectory of response and maintenance of response of atomoxetine in the treatment of child and adult attention-deficit hyperactivity disorder (ADHD). This nonsystematic review includes: onset of action and duration of effect, response rate, effect size, time to optimal response and norepinephrine transporter blockade biomarker data. Atomoxetine can have an onset of action within 1-2 weeks of starting treatment, but there is an incrementally increasing response for up to 24 weeks or longer. Responder rates and effect sizes are similar to methylphenidate. Upon treatment discontinuation, relapse rates are lower than expected. In adults, 50% maintain their response for at least 6 months after stopping atomoxetine, following 6 months of treatment. Single-dose atomoxetine can provide 24-hour efficacy, despite a 5-hour plasma half-life. Hypotheses can be generated relating to neuroadaptive changes, to explain these findings. Atomoxetine has a trajectory of response that is incremental over a long period of time, with a greater than expected maintenance of response. This has implications for physician atomoxetine dosing and efficacy assessment, patient education and outcomes, and for clinical trial design and assessment of comparative efficacy with stimulant medications.

A systems approach to evaluating ionizing radiation: six focus areas to improve quality, efficiency, and patient safety.

Ionizing radiation is an essential component of the care process. However, providers and patients may not be fully aware of the risks involved, the level of ionizing radiation delivered with various procedures, or the potential for harm through incidental overexposure or cumulative dose. Recent high-profile incidents demonstrating the devastating short-term consequences of radiation overexposure have drawn attention to these risks, but applicable solutions are lacking. Although various recommendations and guidelines have been proposed, organizational variability challenges providers to identify their own practical solutions. To identify potential failure modes and develop solutions to preserve patient safety within a large, national healthcare system, we assembled a multidisciplinary team to conduct a comprehensive analysis of practices surrounding the delivery of ionizing radiation. Workgroups were developed to analyze existing culture, processes, and technology to identify deficiencies and propose solutions. Six focus areas were identified: competency and certification; equipment; monitoring and auditing; education; clinical pathways; and communication and marketing. This manuscript summarizes this comprehensive, multidisciplinary, and systemic analysis of risk and provides examples to illustrate how these focus areas can be used to improve the use of ionizing radiation. The proposed solutions, once fully implemented, may advance patient safety and care.

Olanzapine long-acting injection: a review of first experiences of post-injection delirium/sedation syndrome in routine clinical practice.

BACKGROUND: Olanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a cluster of symptoms termed post-injection delirium/sedation syndrome (PDSS) in a small percentage (~2%) of patients during clinical trials. The objective of this analysis was to evaluate the rate and clinical characteristics of PDSS since olanzapine LAI entered commercial use. METHODS: Cases of PDSS were identified from all reported adverse events during worldwide commercial use of olanzapine LAI through to 1 March 2014. Data sources included two ongoing post-marketing safety studies as well as spontaneously reported adverse events from routine clinical practice over a 5-year period (1 March 2009 to 1 March 2014). RESULTS: A total of 338 PDSS events were identified. Of these, 91% occurred within 1 hour of injection, and 52% of these occurred within 15 minutes. None of the PDSS events in this analysis were fatal, and most resolved within 72 hours. The most common symptoms (occurring in >30% of cases) were sedation (61%), confusion (56%), dysarthria (54%), somnolence (46%), dizziness (45%) and disorientation (35%). Overall, PDSS occurred with approximately 0.07% of injections and in 0.46-1.03% of patients (reporting and incidence rates from spontaneous reports and post-marketing safety studies, respectively). CONCLUSIONS: The PDSS events reported during routine clinical use of olanzapine LAI are generally similar in incidence and presentation to those reported in clinical trials. Caution should be applied when interpreting spontaneously reported rates of adverse events, however, due to potential under-reporting. Implemented risk-minimisation activities may contribute substantially to the identification and appropriate management of patients with PDSS in clinical practice.

Efficacy of atomoxetine in adults with attention deficit hyperactivity disorder: an integrated analysis of the complete database of multicenter placebo-controlled trials.

Persistence of attention deficit hyperactivity disorder (ADHD) into adulthood can be disabling or lead to substantial impairment. Several clinical trials of atomoxetine (ATX) in adults with ADHD have been reported following the National Institute for Health and Clinical Excellence (NICE) guidelines issued in 2008. We performed an integrated analysis of all Eli Lilly-sponsored, randomized, double-blind, placebo-controlled studies of ATX in adults with ADHD completed as of May 2012. Individual patient data were pooled from six short-term (10-16 week) studies (1961 patients) and three longer-term (six-month) studies (1413 patients). In the short-term analysis, ATX patients achieved a significantly greater mean reduction in ADHD symptoms than placebo patients (-12.2 vs -8.1; Conners' Adult ADHD Rating Scale-Investigator-Rated: Screening Version (CAARS-Inv: SV); p<0.001). In the longer-term analysis, respective improvements after six months were -13.2 vs -9.7 (p<0.001). Response rates at study endpoints for ATX vs placebo, based on CAARS-Inv: SV improvement ≥ 30% and Clinical Global Impressions of ADHD-Severity (CGI-ADHD-S) ≤ 3 were 34.8% vs 22.3% in the short-term and 43.4% vs 28.0% after six months, and CAARS-Inv: SV improvements ≥ 40% were 41.3% vs 25.3% in the short-term and 44.0% vs 31.4% after six months (all p<0.001). Overall, ATX had a clinically significant effect in adults with ADHD, with reductions in core symptoms and clinically meaningful responder rates.

Systematic review of atomoxetine data in childhood and adolescent attention-deficit hyperactivity disorder 2009-2011: focus on clinical efficacy and safety.

BACKGROUND: Clinicians obtain critical prescribing knowledge from clinical papers and review articles. This is the first published systematic review of clinical atomoxetine data covering 2009-2011. OBJECTIVE: We aim to update clinicians on current clinical atomoxetine data with specific reference to time of onset of efficacy and maximal efficacy. These data may allow critical analysis of comparative efficacy between atomoxetine and stimulant medications. METHODS: A formal systematic review of atomoxetine data from January 2009-June 2011 was conducted. The search term used was "atomoxetine" in the English language. The search yielded 747 citations from which 106 are clinical data. This paper includes clinical efficacy and safety data and excludes quality-of-life and review papers. RESULTS: Atomoxetine has an onset of action within 4 weeks (possibly within 1 week in subsequent responders) but requires at least 12 weeks for full response to be demonstrated. Treatment-naïve cohorts (6-12 weeks) report effect sizes of 0.6-1.3. Using minimum 6-week clinical trial criteria, atomoxetine may demonstrate similar efficacy to methylphenidate comparing reduction in core ADHD symptoms in meta-analysis, although the diversity of the data makes interpretation complex. From epidemiological databases, cardiovascular and suicide-related events were similar to those seen in patients taking methylphenidate. CONCLUSIONS: Incremental response time to atomoxetine should be considered in the design of future comparative efficacy trials.

A 12-week nursing support programme for carers of children and adolescents in the UK with attention deficit hyperactivity disorder prescribed atomoxetine.

INTRODUCTION: Patient support programmes are assuming greater importance in the UK in many therapeutic areas, mostly with the aim of improving adherence to medication and many being provided by the pharmaceutical industry. Atomoxetine is a noradrenaline reuptake inhibitor for the treatment of attention deficit hyperactivity disorder that has recently demonstrated incremental efficacy for at least 12 weeks. Issues of adherence may be predicted over this initial period particularly if adverse events are reported. The Strattera Support Service was initiated in 2006 ( funded by Eli Lilly) to provide advice, initially through telephone contact, by trained nurses during the first 12 weeks of atomoxetine therapy and is offered to carers of patients diagnosed with ADHD after atomoxetine has been prescribed. The aim of this pilot service evaluation is to assess discontinuation rates and compare them with historical control data. METHODS: Data from patients in the service who initiated atomoxetine between 1 January 2009 and 31 March 2010 were analysed to provide a pilot service evaluation. Continuation rates of patients in the service who were taking atomoxetine at week 12 were assessed and compared with historical control data. RESULTS: Between 1 January 2009 and 31 March 2010, 346 patients (300 male patients) enrolled in the programme and commenced treatment with atomoxetine. The mean age of patients was 10.5 years. At 12 weeks, 33 (9.5%) patients had discontinued treatment; continuation rates were similar regardless of age and sex. Discontinuation rates of 39% are reported from historical control data. CONCLUSIONS: Preliminary data from a 12-week atomoxetine patient support programme are supportive that discontinuation rates may be lower than historically expected. Further service evaluations of this programme may be required.

Suicide related events and attention deficit hyperactivity disorder treatments in children and adolescents: a meta-analysis of atomoxetine and methylphenidate comparator clinical trials.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is becoming an increasingly commonly diagnosed and treated childhood illness. Untreated ADHD is recognised as an independent risk factor for suicide-related events and deliberate self-harm and is reported more commonly in these populations. With the treatment of ADHD it is thus crucial to understand further any associations between pharmacological treatments and suicide-related events. Specific data for suicide-related events with stimulants have not been publically reported. Suicidal tendencies are, however, a contraindication to the treatment of patients with methylphenidate. Clinicians and patients may be helped by a meta-analytic comparison of suicide-related events in comparative randomised double-blind atomoxetine and methylphenidate clinical trials. METHODS: Suicide-related events retrospectively mapped to the suicide-related event assessment instrument recommended by the FDA, the Columbia Classification Algorithm for Suicide Assessment (C-CASA), were evaluated in five double-blind placebo controlled comparative studies of atomoxetine and methylphenidate (n = 1024) of 6 to 9 weeks duration. The Mantel-Haenszel risk ratio and Mantel-Haenszel incidence differences have been calculated. RESULTS: In total there were 5 suicide-related events, atomoxetine (ATX) 3/559 and methylphenidate (MPH) 2/465. There were no suicide attempts nor completed suicides. Meta-analysis finds no difference of a difference in risk between ATX and MPH with a Mantel-Haenszel risk ratio of 0.52 (95% CI; 0.06, 4.54). CONCLUSION: In the only reported meta-analysis of comparative suicide-related events between atomoxetine and methylphenidate, no significant evidence of a difference in risk has been found. These data may be informative to clinicians and patients when developing clinical guidelines.

Weight change by baseline BMI from three-year observational data: findings from the Worldwide Schizophrenia Outpatient Health Outcomes Database.

The aim was to explore weight and body mass index (BMI) changes by baseline BMI in patients completing three years of monotherapy with various first- and second-generation antipsychotics in a large cohort in a post hoc analysis of three-year observational data. Data were analyzed by antipsychotic and three baseline BMI bands: underweight/normal weight (BMI <25 kg/m²), overweight (25-30 kg/m²) and obese (>30 kg/m²). Baseline BMI was associated with subsequent weight change irrespective of the antipsychotic given. Specifically, a smaller proportion of patients gained ≥7% baseline bodyweight, and a greater proportion of patients lost ≥7% baseline bodyweight with increasing baseline BMI. For olanzapine (the antipsychotic associated with highest mean weight gain in the total drug cohort), the percentage of patients gaining ≥7% baseline weight was 45% (95% CI: 43-48) in the underweight/normal weight BMI cohort and 20% (95% CI: 15-27) in the obese BMI cohort; 7% (95% CI: 6-8) of the underweight/normal cohort and 19% (95% CI: 13-27) of the obese cohort lost ≥7% baseline weight. BMI has an association with the likelihood of weight gain or loss and should be considered in analyses of antipsychotic weight change.

Weight change from 3-year observational data: findings from the worldwide schizophrenia outpatient health outcomes database.

BACKGROUND: Weight change data from randomized clinical trials are often of limited duration and trials do not always report a full range of clinically relevant categorical end points. METHOD: We conducted a post hoc analysis of data from the observational Worldwide Schizophrenia Outpatient Health Outcomes database (2000-2005) on weight change in 4,626 patients completing 3 years of antipsychotic monotherapy with amisulpride, clozapine, olanzapine, quetiapine, risperidone, and oral and depot first-generation antipsychotics (FGAs). Reported outcomes included mean and categorical weight changes and the trajectories of different measures of weight change. RESULTS: Mean weight gain was lowest with amisulpride (1.8 kg; 95% CI, 0.2-3.3) and highest with olanzapine (4.2 kg; 95% CI, 3.9-4.5). Weight change for all antipsychotics was most rapid during the first 6 months; subsequent weight change was slower but did not plateau. All drugs showed considerable individual variation in weight change. The proportion losing ≥7% of their baseline bodyweight was highest with quetiapine (10%; 95% CI, 7%-16%) and lowest with depot FGAs (5%; 95% CI, 3%-10%). Between 7% and 15% of patients moved into an overweight or obese body mass index (kg/m2)category (≥25). CONCLUSIONS: The degree of weight gain varied between antipsychotics. All antipsychotics were associated with significant (≥7%) weight loss and gain from baseline. The mean rate of weight gain was maximal during the first 6 months but continued over 3 years without a plateau in this specific cohort. Patients should receive regular monitoring of weight throughout treatment.

A systematic review of the safety information contained within the Summaries of Product Characteristics of medications licensed in the United Kingdom for Attention Deficit Hyperactivity Disorder. how does the safety prescribing advice compare with national guidance?

BACKGROUND: The safety of paediatric medications is paramount and contraindications provide clear pragmatic advice. Further advice may be accessed through Summaries of Product Characteristics (SPCs) and relevant national guidelines. The SPC can be considered the ultimate independent guideline and is regularly updated. In 2008, the authors undertook a systematic review of the SPC contraindications of medications licensed in the United Kingdom (UK) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). At that time, there were fewer contraindications reported in the SPC for atomoxetine than methylphenidate and the specific contraindications varied considerably amongst methylphenidate formulations. In 2009, the European Medicines Agency (EMA) mandated harmonisation of methylphenidate SPCs. Between September and November 2011, there were three changes to the atomoxetine SPC that resulted in revised prescribing information. In addition, Clinical Guidance has also been produced by the National Institute for Health and Clinical Excellence (NICE) (2008), the Scottish Intercollegiate Guidelines Network (SIGN) (2009) and the British National Formulary for Children (BNFC). METHODS: An updated systematic review of the Contraindications sections of the SPCs of all medications currently licensed for treatment of ADHD in the UK was undertaken and independent statements regarding contraindications and relevant warnings and precautions were then compared with UK national guidance with the aim of assessing any disparity and potential areas of confusion for prescribers. RESULTS: As of November 2011, there were seven medications available in the UK for the treatment of ADHD. There are 15 contraindications for most formulations of methylphenidate, 14 for dexamfetamine and 5 for atomoxetine. Significant differences exist between the SPCs and national guidance part due to the ongoing reactive process of amending the former as new information becomes known. In addition, recommendations are made outside UK SPC licensed indications and a significant contraindication for methylphenidate (suicidal behaviours) is missing from both the NICE and SIGN guidelines. Particular disparity exists relating to monitoring for suicidal and psychiatric side effects. The BNFC has not yet been updated in line with the European Union (EU) Directive on methylphenidate; it does not include any contraindications for atomoxetine but describes contraindications for methylphenidate that are no longer in the SPC. CONCLUSION: Clinicians seeking prescribing advice from critical independent sources of data, such as SPCs and national guidelines, may be confused by the disparity that exists. There are major differences between guidelines and SPCs and neither should be referred to in isolation. The SPC represents the most relevant source of safety data to aid prescribing of medications for ADHD as they present the most current safety data in line with increased exposure. National guidelines may need more regular updates.

Olanzapine long-acting injection: insights from an early case series in the UK.

OBJECTIVE: Olanzapine long-acting injection depot (OLAI) has been licensed in the UK since 2008. As a result of the recognition during clinical trials that in 0.07% of injections there may be inadvertent intravenous administration leading to post-injection delirium/sedation syndrome (PDSS), the licence mandates a 3 h observation after each injection and accompaniment of the patient to their final destination. The administration of OLAI may thus necessitate organization of local service provisions. We report on how a single healthcare facility in Northern Ireland has treated three initial patients and present a brief case series on these patients and their clinical outcomes. METHODS: In the first three patients with schizophrenia to receive OLAI, the clinical notes were retrospectively examined to provide clinical data. RESULTS: All three patients had acceptable clinical outcomes showing sustained clinical improvement and have continued on OLAI for over 1 year. Observation has been undertaken within an existing daycare unit staffed by nursing staff and occupational therapists for 3 h after each injection. No issues have emerged from the use of this service that has also provided educational and psycho-educational programmes for the patients. No cases of post-injection delirium/sedation syndrome were reported. There have been no additional cost implications. CONCLUSIONS: In patients for whom OLAI may be clinically indicated, the utilization of an existing service to provide the 3 h of observation after each injection may represent a solution with a cost-neutral outcome.