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.

Weight Gain Risk Factor assessment checklist: overview and recommendation for use.

OBJECTIVES: Patients with mental illness are at risk for weight gain. Evidence-based risk assessment checklists have the potential to identify patients at risk early in treatment and improve patient outcomes. METHODS: The 16-item Weight Gain Risk Factor (WGRF-16) checklist has been developed as a simple brief assessment of key weight gain risk factors during antipsychotic treatment. It consists of factors that were collected on the basis of published research on predictors to be assessed at initiation of, and early in treatment with antipsychotics. RESULTS: The factors in the WGRF-16 checklist included age, sex, body mass index, race, appetite, energy intake, a diagnosis of undifferentiated schizophrenia, early clinical response, comorbiditites, social activity, patient insight, housing conditions, weight satisfaction, eating habits, and physical activity level. The WGRF-16 is designed to be repeated 2-3 weeks after initiation of treatment to help to predict an individual's risk of clinically significant weight gain (>7%) during long-term treatment. Further research is required to assess the predictive validity of the checklist. CONCLUSIONS: The WGRF-16 checklist is not intended to replace other required monitoring of patients with severe mental disorders but is a facilitator of weight monitoring in conjunction with clinical guidelines.

Schizophrenia and cancer: in 2010 do we understand the connection?

OBJECTIVE: in recent years, there has been a plethora of cancer mortality and incidence data reported in schizophrenia. Despite this, there has been little focus on cancer in schizophrenia guidelines. Additionally, there have been suggestions that schizophrenia may provide inherent protection against cancer. The goal of this review is to establish, using recent data, the incidence and mortality rates for cancer in schizophrenia. METHOD: we identified systematic reviews and meta-analyses and undertook a search using the Medical Subject Headings' entry terms schizophrenia and neoplasm. RESULTS: incidence and mortality rates for cancer in schizophrenia are increased, compared with relevant general populations. Data are not uniformly reported and cohort ages tend to be young for expected cancer incidence. Despite the young cohort ages, the incidence of the major cancers-lung and breast-are substantially increased. Confounders are often not measured in the epidemiologic databases. When lung cancer is adjusted for smoking rates, there appears to be a lower risk of lung cancer than expected providing some basis to support an inherently reduced risk of cancer. There may also be a dissonance between incidence and mortality rates that suggest a prejudice against either diagnosis or treatment of these vulnerable patients. CONCLUSION: a single definitive study of schizophrenia and cancer is unfeasible, and future research will lean heavily on systematic review and meta-analysis. Researchers should report cancer data to include age and follow-up data and cohort overlap. Cancer accounts for almost an equivalent mortality as cardiovascular disease.

A review of the association between antipsychotic use and hyperprolactinaemia.

Recent evidence linking hyperprolactinaemia to longer-term clinical sequelae, including osteoporosis, hip fractures and possibly breast cancer, is increasing clinical awareness of the relevance of hyperprolactinaemia. A review of the literature finds clinical trials reporting some degree of comparative prolactin data among antipsychotics. Many of the randomised clinical trials (RCTs) do not report categorical rates of hyperprolactinaemia in contrast with the naturalistic studies, making it complex for clinicians to evaluate the extent and severity of hyperprolactinaemia. Hyperprolactinaemia is one of the commonest adverse events reported in clinical trials and can be found in association with all antipsychotics. The highest rates of hyperprolactinaemia are reported in association with risperidone and amisulpride, often as high as 80-90% of all female subjects and consistently greater than with the typical antipsychotics. Significant rates of hyperprolactinaemia of lesser severity and more transience have also been reported in association with other atypical antipsychotics.

Categorical prevalence and severity of hyperprolactinaemia in two UK cohorts of patients with severe mental illness during treatment with antipsychotics.

Hyperprolactinaemia may be associated with hidden longer-term consequences, such as osteoporosis, bone fractures, pituitary tumours and breast cancer. Prolactin data from clinical trials is not always reported in a categorical manner and does not always allow the risk of hyperprolactinaemia to be evaluated for specific patient cohorts. Patients participating in a physical health management programme in the UK for severe mental illness patients--the Well-being Support Programme--had prolactin measurements made regardless of symptoms. Prolactin data from the complete cohort of 178 patients receiving antipsychotics in Leeds and London are reported. Hyperprolactinaemia was measured in 33.1% but more commonly in females than males (47.3% and 17.6%) and was associated with all antipsychotics except clozapine. The highest prevalence rates were found in amisulpride (n=20) 89%, risperidone long-acting intramuscular injection (LAIM) 67% (n=6) and risperidone (n=30) 55% used as antipsychotic monotherapy. Clinically Significant hyperprolactinaemia (>1000 mIU/L approximately 47 ng/ml) was measured in 15.8% of patients, predominantly in females. Levels >2000 mIU/L approximately 95 ng/ml in 6.2% of the complete cohort. Clinicians may wish to add prolactin measurement to the routine laboratory parameters currently measured for some antipsychotics and should be advised of the potential longer-term consequences of hidden hyperprolactinaemia.

Weight management in a cohort of Irish inpatients with serious mental illness (SMI) using a modular behavioural programme. A preliminary service evaluation.

BACKGROUND: Weight gain is commonly observed during psychotropic treatments for chronic forms of severe mental illness and is most rapid during the early treatment phases. All formats of behavioural weight intervention programmes have suggested that weight gain can be prevented or reversed in some patients. There is no data on these programmes in acutely unwell inpatients whom may be the major beneficiaries. METHODS: A modular behavioural intervention programme (Solutions for Wellness) used in SMI outpatients since 2002 in Ireland has been adapted for inpatient use. Preliminary data is reported from 5 centres in Ireland. RESULTS: In 47 inpatients the mean weight change was +0.26 kg (SD 2.02) with a median change of 0 kg. Mean follow-up was 23.7 (SD 21.6) days, and median 14 days (range 6-98 days). There was no difference in mean weight change in those patients involved for > 35 days compared with < 35 days (+0.26 kg; 0.25 kg; p = 0.5). Weight loss or maintenance was seen in 70% of patients. CONCLUSION: These preliminary data are supportive of the concept that acutely unwell inpatients with SMI may engage with a behavioural weight programme. Weight change observed contrasts with the significant weight gain often seen in most subjects. Further clinical trials are warranted.

Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics.

Hyperprolactinaemia is a common finding in patients treated with antipsychotics. A complete cohort of 194 schizophrenia and bipolar disorder patients receiving antipsychotics in a single community mental health trust in Halifax UK underwent routine prolactin screening in the absence of any reLevant symptomatoLogy. Values above the upper limit of normal were measured in 38% of the cohort and were more common in females (52%) than males (26%). Significantly elevated levels (>1000 mIU/l) were measured in 21% of the cohort. Risperidone monotherapy treatment was associated with hyperprolactinaemia in 69% of patients ( n = 35) and in 100% of female patients (n = 16) and amisulpride monotherapy in 100% (n = 7). Prolactin screening is not currently undertaken routinely in the UK. These data give some indication of prevalence of varying degrees of hyperproLactinaemia that might be found when screening an asymptomatic cohort of schizophrenia and bipolar outpatients. Clinicians may be helped by the reporting of such categorical data from clinical trials in addition to mean cohort values of prolactin. Long-term hyperprolactinaemia may be associated with clinical sequeLae in some patients.

A well-being programme in severe mental illness. Reducing risk for physical ill-health: a post-programme service evaluation at 2 years.

INTRODUCTION: Cardiovascular disease is more prevalent in patients with severe mental illness (SMI) than in the general population. METHOD: Seven geographically diverse centres were assigned a nurse to monitor the physical health of SMI patients in secondary care over a 2-year period in the "Well-being Support Programme" (WSP). A physical health screen was performed and patients were given individual weight and lifestyle advice including smoking cessation to reduce cardiovascular risk. RESULTS: Nine hundred and sixty-six outpatients with SMI >2 years were enrolled. The completion rate at 2 years was 80%. Significant improvements were observed in levels of physical activity (p<0.0001), smoking (p<0.05) and diet (p<0.0001). There were no changes in mean BMI although 42% lost weight over 2 years. Self-esteem improved significantly. Low self-esteem decreased from 43% at baseline to 15% at 2 years (p<0.0001). At the end of the programme significant cardiovascular risk factors remained, 46% of subjects smoked, 26% had hypertension and 81% had BMI >25. CONCLUSION: Physical health problems are common in SMI subjects. Many patients completed 2 years follow up suggesting that this format of programme is an acceptable option for SMI patients. Cardiovascular risk factors were significantly improved. Interventions such as the Well-being Support Programme should be made widely available to people with SMI.

Intramuscular Olanzapine - a UK case series of early cases.

BACKGROUND: Clinical trials assessing efficacy and safety of Intramuscular (IM) Olanzapine in acute schizophrenia and acute mania have previously been undertaken in studies required for drug registration in patients who were required to give informed consent. These patients may have less severe forms of psychosis than patients treated in routine practice. Data derived from naturalistic practice following the launch of IM olanzapine may be helpful for clinicians in assessing efficacy and safety of IM olanzapine. The PANSS-EC scale used in the clinical studies may represent a tool that could be used in routine clinical practice. CASE PRESENTATION: We report on an early unselected case series of 7 patients who received IM olanzapine in routine clinical practice settings in the UK. In this case series, olanzapine IM was generally effective, and no adverse events were reported. Adjunctive benzodiazepines were given concomitantly in 1 of the 7 subjects. This is relevant as concomitant benzodiazepines are not recommended for a minimum of 1 hour post IM olanzapine administration. PANSS-EC data was collected in 2 of the 7 subjects. CONCLUSION: Although patients had greater severity of psychosis than clinical trial patients there were no unexpected findings. In addition the PANSS-EC scale is a scale that may be useful in assessing the efficacy of IM antipsychotics in routine clinical practice.

Measurement of long-term outcomes in observational and randomised controlled trials.

BACKGROUND: Randomised controlled trials (RCTs) are the gold standard for evaluating treatment efficacy. However, the outcomes of RCTs often lack clinical utility and usually do not address real-world effectiveness. AIMS: To review how traditional RCTs may be triangulated with other methodologies such as observational studies and pragmatic trials by highlighting recently reported studies, outcomes used and their respective merits. METHOD: Literature review focusing on drug treatment. RESULTS: Recently reported observational and some pragmatic studies show a degree of consistency in reported results and use outcomes that have face validity for clinicians. CONCLUSIONS: No single experimental paradigm or outcome provides the necessary data to optimise treatment of mental illness in the clinical setting.

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.

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 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.

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.

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.

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.

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.