Marta Casillas

Underdiagnosis of Attention-Deficit/Hyperactivity Disorder in Adult Patients: A Review of the Literature

Objective: To raise awareness of attention-deficit/hyperactivity disorder (ADHD) as an underdiagnosed, undertreated, often comorbid, and debilitating condition in adults. Data Sources: PubMed was searched using combinations of keywords, including ADHD, adult, diagnosis, identify, prevalence, and comorbid, to find articles published between 1976 and 2013. Study Selection: In total, 99 articles were selected for inclusion on the basis of their relevance to the objective and importance to and representation of ADHD research, including international guidelines for adults with ADHD. Results: In a large proportion of children with ADHD, symptoms persist into adulthood. However, although adults with ADHD often experience chaotic lifestyles, with impaired educational and vocational achievement and higher risks of substance abuse and imprisonment, many remain undiagnosed and/or untreated. ADHD is usually accompanied by other psychiatric comorbidities (such as major depressive disorder, anxiety disorder, and alcohol abuse). Indeed, adults with ADHD are more likely to present to a psychiatric clinic for treatment of their comorbid disorders than for ADHD, and their ADHD symptoms are often mistaken for those of their comorbidities. Untreated ADHD in adults with psychiatric comorbidities leads to poor clinical and functional outcomes for the patient even if comorbidities are treated. Effective treatment of adults’ ADHD improves symptoms, emotional lability, and patient functioning, often leading to favorable outcomes (eg, safer driving, reduced criminality). A few medications have now been approved for use in adults with ADHD, while a multimodal approach involving psychotherapy has also shown promising results. Conclusions General psychiatrists should familiarize themselves with the symptoms of ADHD in adults in order to diagnose and manage ADHD and comorbidities appropriately in these patients.

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

BackgroundOlanzapine 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.MethodsCases 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).ResultsA 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).ConclusionsThe 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.

Influence of route of administration/drug formulation and other factors on adherence to treatment in rheumatoid arthritis (pain related) and dyslipidemia (non-pain related)

Abstract Objectives: A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). Research design and methods: Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months’ follow up. Main outcome measures: Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. Results: A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1–3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support. Conclusions: The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA. Limitation: The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and diseases difficult.

Switching to olanzapine long-acting injection from either oral olanzapine or any other antipsychotic: comparative post hoc analyses

Background A considerable proportion of patients suffering from schizophrenia show suboptimal responses to oral antipsychotics due to inadequate adherence. Hence, they are likely to benefit from switching to a long-acting injectable formulation. These post hoc analyses assessed the clinical effects of switching to olanzapine long-acting injection (OLAI) from either oral olanzapine (OLZ) or other antipsychotics (non-OLZ). Methods Post hoc analyses were done based on two randomized studies (one short-term, one long-term) conducted in patients suffering from schizophrenia and treated with OLAI. The short-term study was an 8-week placebo-controlled, double-blind trial in acute patients, and the long-term study was a 2-year, oral olanzapine-controlled, open-label, follow-up of stabilized outpatients. Results These analyses used data from 62 OLAI-treated patients (12 switched from OLZ, 50 from non-OLZ) from the short-term study and 190 OLAI-treated patients (56 switched from OLZ, 134 from non-OLZ) from the long-term study. Kaplan–Meier survival analyses of time to all-cause discontinuation of OLAI treatment did not differ significantly between OLZ and non-OLZ patients in the short-term study (P=0.209) or long-term study (P=0.448). Similarly, the proportions of OLZ and non-OLZ patients that discontinued OLAI were not statistically different in the short-term (16.7% versus 36.0%, respectively; P=0.198) or long-term (57.1% versus 47.8% respectively; P=0.238) studies. In the short-term study, no significant differences were detected between the patient groups in mean change in Positive and Negative Syndrome Scale (PANSS) total score (−13.4 OLZ versus −20.8 non-OLZ; P=0.166). In the long-term study, mean change in PANSS total score (3.9 OLZ versus −3.6 non-OLZ; P=0.008) was significantly different between the non-OLZ and OLZ groups. Rates of treatment-emergent adverse events were similar in OLZ and non-OLZ groups per study. Conclusion These post hoc analyses suggest that no significant differences in clinical effectiveness were seen after switching from non-OLZ or OLZ to OLAI. However, these findings should be interpreted with care, due to small sample sizes and differences in patients’ clinical profiles.

FRI0565 Influence of Route of Administration/drug Formulation and Other Factors on Compliance with Treatment in Rheumatoid Arthritis and Dyslipidaemia

Background Poor compliance with drugs for rheumatoid arthritis (RA) can lead to treatment failure, delayed recovery, disease progression and a need for more aggressive therapy. Understanding factors associated with poor compliance has potential to improve treatment outcomes. Objectives A comprehensive review was performed to investigate: the effect of route of administration on drug compliance in RA; compliance with oral drugs in RA compared with that in a non-pain-related disease (dyslipidaemia); the effect of poor compliance on clinical outcomes; the relationship between compliance and economic outcomes, such as healthcare resource utilisation and costs; and the impact of patient education/support programmes on compliance. Methods Comprehensive database searches and searches of the reference lists of relevant publications were performed to identify studies investigating drug compliance in adults with RA being treated with conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidaemia being treated with statins. Studies had to be published after 1998 and in English, and had to involve ≥6 months of follow up. Compliance data were extracted and compared between the different routes of drug administration in RA, and between the two diseases for oral agents. Results A total of 33 and 22 papers underwent data extraction for RA and dyslipidaemia, respectively. The definitions and range of compliance values across studies was wide, making comparisons between drug formulations and diseases difficult. Within the constraints of the analysis, compliance and persistence rates were broadly similar for the different routes of drug administration in RA (compliance for intravenous [i.v.], subcutaneous [s.c.] and oral drugs, respectively: 68%, 59–73% and 33–107% [some patients took extra doses] at 6 months; 38–64% [i.v.] and 16–97% [s.c.] at 1 year; and 58–71% [oral] at 2 years). Compliance with oral drugs was also broadly similar across the two diseases (for RA: 33–107% at 6 months, 58–71% at 2 years; for dyslipidaemia: 40–100% at 6 months, 72–75% at 2–3 years). Poor compliance had clinical consequences in both diseases: greater disease activity, pain and functional disability in RA, and increased serum cholesterol levels and risk of ischaemic heart disease in dyslipidaemia (Figure). The only factors associated with compliance/persistence across both diseases were age, race and the extent of copayment/out-of-pocket expenses. Over 1–3 years, poor compliance with biologic RA drugs led to increased resource use and medical costs but lower total direct costs due to reduced biologic (s.c. and i.v.) drug costs. By contrast, poor compliance with dyslipidaemia drugs resulted in increased total direct costs. For RA, compliance improved with patient education/support. Conclusions The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug compliance in RA. Disclosure of Interest B. Fautrel: None declared, A. Balsa: None declared, P. Van Riel: None declared, M. Casillas Employee of: Employee of Eli Lilly and Company, J.-P. Capron Employee of: Employee of Eli Lilly and Company, C. Cueille Employee of: Employee of Eli Lilly and Company, I. De La Torre Employee of: Employee of Eli Lilly and Company