Effect of transitioning from extended-release methylphenidate onto osmotic, controlled-release methylphenidate in children/adolescents with ADHD: results of a 3-month non-interventional study.

BACKGROUND: To explore the clinical outcomes of children/adolescents with ADHD who transitioned from extended-release methylphenidate (ER MPH, Medikinet Retard) to osmotic release oral system (OROS) MPH (Concerta). Medikinet Retard is a registered trade name of Medice, Bad Iserlohn, Germany. Concerta is a registered trade name of Janssen-Cilag GmbH, Neuss, Germany. METHODS: This prospective, non-interventional study included patients aged 6 to 18 years with a confirmed diagnosis of ADHD who experienced insufficient clinical response and/or poor tolerability on ER MPH. Patients transitioned onto OROS MPH and were followed for 12 weeks. Symptoms, functional outcome, health-related quality of life, safety and tolerability were assessed. RESULTS: 180 patients were included in the intention-to-treat analysis. The mean ER MPH dose before switching was 28.2 mg/day; mean OROS MPH starting dose was 38.1 mg/day, increasing to 41.2 mg/day at the final visit. Mean treatment duration was 79.49 ± 24.22 days (median 85; range 7-136). Several symptomatic and functional outcomes under OROS MPH treatment changed from baseline and included the Conners' Parent Rating Scale (CPRS; -11.7 ± 11.3; p < 0.0001), C-GAS (12.3 ± 15.2; p < 0.0001) and ILC-LQ0-28 (parents' rating 2.9 ± 4.3 and patients' rating 2.8 ± 3.8; both p < 0.0001). Improvements in social interactions, playing with other children, doing household chores, or school homework, going to bed, and behavior towards visitors/at visits were noted (p < 0.0001). Approximately 40% of patients reported better sleep quality and appetite (p < 0.0001), and 72.8% expressed satisfaction with OROS MPH therapy compared to previous ER MPH. OROS MPH was well tolerated; the most common AEs after switching, with an incidence >2% and possibly related to therapy, were involuntary muscle contractions (tics; 8.9%), insomnia (7.2%) and anorexia (5.0%). No relevant changes in body weight or vital signs were observed. Three patients reported four serious AEs, but none were considered related to OROS MPH. Limitations included those associated with the uncontrolled, open-label design, possible inclusion bias and non-validation of the CPRS in a German population. CONCLUSIONS: Transitioning onto OROS MPH improved functionality, symptom control and decreased burden of disease in patients with ADHD who had insufficient response to, and/or poor tolerability of ER MPH. Similarly, care givers benefited from patients' treatment and reported significant reduction in their burden of disease and improvement of their quality of life upon the child's transition onto OROS MPH.

Long-term assessment of topiramate for epilepsy: an open-label, single-arm, multicentre, prospective study in a naturalistic setting.

BACKGROUND AND OBJECTIVE: Most patients with epilepsy require long-term medical therapy. Newer antiepileptic drugs (AEDs) appear to be overall similarly effective to older agents but may be better tolerated. However, most of the clinical data available for newer AEDs derive from a number of short-term studies. The objective of this study was to explore long-term outcomes in patients with epilepsy treated with topiramate in routine clinical practice. METHODS: This was an open-label, multicentre, optional follow-up monotherapy study that included adolescents and adults with epilepsy who completed two similarly designed 28- or 30-week studies and agreed to participate for an additional 52 weeks. Seizure types and frequency, topiramate dose, vital signs and treatment-emergent adverse events (TEAEs) after 12, 26, 39 and 52 weeks were documented. Post hoc analyses to explore differences between males and females were conducted. RESULTS: 114 patients (49.0% women, mean ± SD age 43 ± 17.5 years) with a mean ± SD disease duration of 61 ± 118 months (men 54 ± 96 vs women 68 ± 138 months) were followed up for a median of 18.5 months. Seventy-eight percent of patients completed the study. Reasons for premature discontinuation were: loss to follow-up (10.5%), TEAE (5.3%), lack of efficacy (2.6%), non-adherence (0.9%) and other reasons (4.4%). Seizure frequency per 4 weeks decreased from a mean ± SD 5.0 ± 28.3 at baseline to 0.6 ± 2.1 during the whole observation period. Fifty-four patients (52.9%) were seizure free during the whole observation period. In addition, 69 of 95 patients (72.6%) whose topiramate therapy was stable within a range of ±50 mg/day for a period of at least 12 months (maintenance phase) were seizure free while treated with a median topiramate dose of 100 mg/day. The most frequently reported TEAEs were paraesthesias (13.2% of patients), dizziness (7.0%) and seizure-related events (7.0%). No significant differences between males and females were found for treatment response or retention. CONCLUSION: Topiramate is an effective and well tolerated long-term treatment option for adolescents and adults with epilepsy.

Exploring the impact of once-daily OROS® methylphenidate (MPH) on symptoms and quality of life in children and adolescents with ADHD transitioning from immediate-release MPH.

OBJECTIVES: To explore the clinical and health-related quality of life (HRQoL) outcomes in children/adolescents with attention-deficit/hyperactivity disorder (ADHD) who required a therapy switch from immediate-release (IR) methylphenidate (MPH) and were initiated on Osmotic Release Oral System (OROS(®)) MPH. METHODS: Prospective, noninterventional study including patients (aged 6-18 years) with a confirmed diagnosis of ADHD who transitioned from IR MPH to OROS(®) MPH based on medical needs. Patients were transitioned to OROS(®) MPH and were followed for 12 weeks. Attention-deficit/hyperactivity disorder symptoms, functional outcomes, HRQoL, and tolerability were assessed throughout the study. RESULTS: 598 patients entered the intention-to-treat analysis. The mean OROS(®) MPH starting dose was 29.5 ± 12.0 mg/day, increasing slightly to 33.5 ± 13.2 mg/day at final visit. Compared with baseline, there were significant (all P < 0.0001) symptomatic, functional, and HRQoL improvements after transitioning from IR MPH to OROS(®) MPH as assessed by the Conners' Parent Rating Scale (from 29.0 ± 10.5 to 19.5 ± 11.1), Children's Global Assessment Scale (by 11.0 ± 13.3), and Inventory for Assessing Quality of Life (ILC) LQ0-28 scores (parents' rating from 17.2 ± 3.9 to 19.4 ± 4.0; patients' rating from 18.7 ± 4.0 to 20.5 ± 3.9). Overall, no significant changes in quality of sleep or appetite were observed. More than 70% of parents and physicians rated the effectiveness of OROS(®) MPH as at least "good" and were at least "satisfied" with OROS(®) MPH. The most common treatment-emergent adverse events were insomnia and anorexia. No clinically relevant changes in body weight or vital signs were observed. CONCLUSIONS: In this naturalistic setting, transitioning from IR MPH to OROS(®) MPH, in patients who showed previously insufficient response and/or poor tolerability, was successful. Patients' and parents' HRQoL as well as burden of disease showed a clinically relevant improvement. OROS(®) MPH was generally safe and well tolerated.

Improved functionality, health related quality of life and decreased burden of disease in patients with ADHD treated with OROS® MPH: is treatment response different between children and adolescents?

BACKGROUND: To compare clinical and health-related quality of life (HRQoL) outcomes between children and adolescents with ADHD treated with OROS® MPH, using data from two large similarly-designed multicenter, prospective, open-label, single-arm, non-interventional studies. METHODS: Pooled analysis (42603ATT4037, 42603 - ATT - 4001) including patients (6 to 18 years) with a confirmed diagnosis of ADHD. Patients were treated with OROS® MPH for 12 weeks; ADHD symptoms, functioning, HRQoL, safety and tolerability parameters were assessed. RESULTS: 822 patients (583 children [6-12 years], 239 adolescents [13-18 years]) were included in the pooled analysis. Mean daily OROS® MPH starting doses in the child and adolescent subgroups were 29.0 ± 11.7 and 37.6 ± 15.6 mg, respectively (p < 0.001). At study end (week 12), the overall mean daily dose was 35.5 ± 14.0 mg, with children and adolescents receiving 32.8 ± 12.7 and 42.0 ± 15.1 mg/day, respectively (p < 0.001). Significant (p < 0.0001: overall population, children, adolescents) symptomatic, functional and HRQoL improvements were observed from baseline to study end using the Conners' Parents Rating Scale (overall: 29.2 ± 10.7 [baseline] to 19.3 ± 11.3 [endpoint]), Children's Global Assessment Scale (overall: 58.5 ± 14.5 [baseline] to 69.6 ± 16.1 [endpoint]), and ILC-LQ0-28. At week 12, between-age group differences were seen in the individual ILC-LQ0-28 parameters: school performance (p = 0.001 [parents' assessment], p = 0.032 [childrens' assessment]), global QoL (p = 0.012 [parents']) and interests and hobbies (p = 0.023 [childrens']). Treating physician's planned continued use of OROS® MPH in 76.9%, 86.0% and 79.3% of children, adolescents and the total population, respectively, at study end (p = 0.029 between-age subgroups). 195 of 822 patients (23.7%) experienced at least one treatment-emergent adverse event; most commonly reported AEs in the total group (≥4%) were insomnia (7.2%), anorexia (4.3%) and involuntary muscle contractions (4.1%). No clinically relevant changes in body weight or vital signs were observed. CONCLUSIONS: Clinically relevant differences between children and adolescents with ADHD are present. Adolescents appeared to have a lower health related quality of life and functioning compared to children at baseline, however, they were able to reach comparable ratings at endpoint for most items. Similarly, burden of disease decreased in patients and their carers. OROS MPH was generally safe and well tolerated.

Transitioning to OROS(®) methylphenidate from atomoxetine is effective in children and adolescents with ADHD.

OBJECTIVE: To explore the clinical outcomes of children/adolescents with attention-deficit/hyperactivity disorder (ADHD) who required a therapy switch from atomoxetine to OROS(®) methylphenidate (MPH). METHODS: This prospective, noninterventional study involved patients aged 6-18 years with a confirmed diagnosis of ADHD who experienced insufficient clinical response and/or poor tolerability during atomoxetine treatment. Patients were transitioned to OROS MPH and followed for 12 weeks. ADHD symptoms, functional outcomes, health-related quality of life (HRQoL) and tolerability were assessed throughout the study. RESULTS: 42 patients (intention-to-treat) transitioned from atomoxetine 43.2 plus 14.7 mg onto OROS MPH 33.0 plus 17.7 mg (mean daily starting dose), increasing to 38.6 plus 17.6 mg at the final visit. Median treatment duration was 85 days (range: 3-155). Compared with baseline, symptoms, functional outcome and HRQoL improved after transitioning to OROS MPH as assessed by the Conners' Parent Rating Scale (mean change from baseline: -10.1 ± 11.6; p < 0.0001), Children's Global Assessment Scale (8.7 ± 16.2; p = 0.0015) and ILC-LQ0-28 scores (parents' rating from 14.9 ± 3.6 [baseline] to 17.5 ± 4.8 [study end]; p = 0.0002; patients' rating from 16.9 ± 3.9 [baseline] to 19.3 ± 4.4 [study end]; p = 0.0003). Social interactions and late afternoon tasks (playing with other children, household chores, school homework and behavior towards visitors/at visits) improved (p < 0.001). Approximately 62% expressed satisfaction ('very good' or `good') with OROS MPH therapy compared with prior atomoxetine with respect to symptom control in the late afternoon. The most common treatment-emergent adverse events after switching were involuntary muscle contractions (tics; 16.7%), insomnia (14.3%), abdominal pain (9.5%) and headache (9.5%). No clinically relevant changes in body weight or vital signs were observed. CONCLUSION: In this naturalistic setting, transitioning from atomoxetine to OROS MPH was associated with improved ADHD symptoms and impacted positively on patients' and parents' HRQoL and disease burden in ADHD children who demonstrated an insufficient response and/or poor tolerability to atomoxetine.

Use of recombinant human parathyroid hormone(1-84) in patients with postmenopausal osteoporosis: a prospective, open-label, single-arm, multicentre, observational cohort study of the effects of treatment on quality of life and pain--the PROPOSE study.

BACKGROUND AND OBJECTIVE: Osteoporosis is a progressive bone disorder. Its medical therapy typically involves calcium, vitamin D and antiresorptive drugs. The anabolic parathyroid hormones (PTHs) represent a major advance since they stimulate new bone formation. Two forms of recombinant human PTH (rhPTH) have been evaluated: the 34-amino acid fragment rhPTH(1-34) and the intact 84-amino acid form rhPTH(1-84), the latter being marketed as Preotact®. Osteoporosis leads to increased bone fragility and susceptibility to fracture. Additionally, the disease is often accompanied by pain and a reduced quality of life (QOL). These aspects have rarely been addressed in previously published studies of PTH, which have instead focused on bone density and fractures. The aim of the present study was to evaluate therapy with rhPTH(1-84) in the treatment of osteoporosis in postmenopausal women under everyday practice conditions with emphasis on patients' QOL and pain. METHODS: The study was performed as a prospective, open-label, single-arm, multicentre, observational cohort study that included postmenopausal women in whom treatment with rhPTH(1-84) was newly initiated. Patients were to be treated with rhPTH(1-84) for 12 months at a dose of 100 µg, administered once daily as a subcutaneous injection. The primary efficacy endpoint was the total score on the Quality of Life Questionnaire of the European Foundation for Osteoporosis, 41-item version (QUALEFFO-41). Secondary efficacy criteria were QUALEFFO-41 subscale scores, patients' assessments of pain on visual analogue scales (range 0-100), and performance on the chair rising test. RESULTS: 112 patients were included in the safety and in the intent-to-treat (ITT) efficacy analyses. Sixty-six patients finished the 1-year period (per-protocol group). All ITT patients were female with a mean age of 72 years and a mean duration of osteoporosis of 73 months. During the study, all QUALEFFO-41 scales improved significantly: in the ITT group, the mean total score improved from 49.8 to 41.3 points. In the ITT population, mean pain at rest improved significantly by about 20% and mean pain on movement by about 36%. When patients who took at least one dose of pain medication were compared with those who took no pain medication during the study, it was evident that pain reduction did not occur only as a result of taking pain medication: use of rhPTH(1-84) was associated with a similar pain reduction in both subgroups. The most frequent adverse events (AEs) were hypercalcaemia (12.5% of patients) and nausea and vomiting (10.7% of patients). AEs caused 16% of patients to discontinue during the 12-month study period. CONCLUSION: This 12-month study carried out in a typical sample of postmenopausal women with osteoporosis showed that treatment with rhPTH(1-84) is safe. The present study, which is one of the first to investigate QOL and pain during PTH treatment systematically, also showed that rhPTH(1-84) improves QOL and reduces pain, thereby reducing the burden of osteoporotic symptoms for patients. These results, however, need to be verified in a controlled clinical trial. [ClinicalTrials.gov Identifier: NCT00515593].

Topiramate in patients with epilepsy and intellectual disability.

This noninterventional single-arm study explored effectiveness and behavioral outcomes in intellectually disabled patients treated with topiramate for epilepsy. Data from 21 patients diagnosed with cerebral palsy were available for evaluation. Behavioral changes were assessed using the validated Aberrant Behavior Checklist and Matson Evaluation of Social Skills for Individuals with Severe Retardation (MESSIER) scales. Some improvement in nearly all behavioral aspects was observed under concomitant topiramate therapy; for example, the Aberrant Behavior Checklist total score changed from 33.7+/-25.8 to 25.3+/-19.1 (P=0.047). In addition, seizure frequency decreased from 16.1+/-22.2/4 weeks to 12.2+/-17.0/4 weeks (N=21, P=0.164). Fifty-two percent of the patients experienced at least 50% seizure reduction during the 24-week treatment period. The safety profile is in accordance with the current Summary of Product Characteristics of Topiramate. Two unexpected deaths were attributed to sudden unexpected death in epilepsy.

Validation of the factorial structure of the Positive and Negative Syndrome Scale in use by untrained psychiatrists in routine care.

Background. The Positive and Negative Syndrome Scale (PANSS) can be called the standard for the assessment of schizophrenic disorders. It is well-known and routinely used. In scientific studies and clinical practice extensive training of raters in the use of the scale can often not be provided. The question is whether under such conditions psychometric properties of the scale can be guaranteed. Method. In a 2-year drug utilization study on risperidone, 1895 schizophrenic outpatients were assessed by their treating psychiatrists, who were working under conditions of routine care, using a modified version of the Positive and Negative Symptom Scale (PANSS/m). Physicians could not be trained in the use of the scale. The results of these ratings were analysed, comparing means and internal consistency with the original Kay et al. results (Kay et al. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261), and by factor analysis for the total sample and split halves. Results. Means for the positive subscale were similar (6.5 and 6.4, respectively) and means for the negative subscale (11.9 and 8.0, respectively) slightly higher than the original Kay et al. results. Internal consistency of the positive and negative subscales (0.80 and 0.87, and 0.73 and 0.83, respectively) were similar to Kay et al. The same clear factorial solution was found for the total sample and the subsamples. Discussion. Scores for the subscales reflect the predominance of negative symptoms in schizophrenic outpatients. The factorial solution supports the positive and negative subscales of the PANSS. The PANSS/m was easy to use under conditions of routine treatment and is a good and robust scale.

[Switching from a short-acting to a long-acting methylphenidate preparation: a multicentre, open study in children with ADHD]. / Umstellung von einem unretardierten auf ein retardiertes Methyl phenidatpräparat: Eine multizentrische, offene Studie an Kindern mit ADHS.

OBJECTIVES: The objective was to evaluate the safety and efficacy of a switch in medication to a single daily dose of OROS-Methylphenidate (OROS-MPH, Concerta) in clinically stable children and adolescents with ADHD. METHODS: A prospective, multi-centre open-label study was carried out for a period of three weeks in 213 patients aged 6-16 years with ADHD who had previously been treated with IR-MPH. Their medication was switched to a single daily dose of OROS-MPH. Primary endpoints were changes in the IOWA Conners Inattention/Overactivity Subscale and the global assessment of efficacy as rated by parents and teachers. The safety of the medication was evaluated by means of recording adverse events. The development of weight, sleep quality, and appetite were also observed. RESULTS: Switching the medication from IR-MPH to OROS-MPH resulted in a significant positive effect as evidenced by caregivers' ratings of core symptoms. Corresponding ratings by teachers revealed no significant difference from baseline values. The global efficacy was rated by teachers as "good" or "excellent" for 55% of the cases, by caregivers for 79% thereof, and by investigators in 77% of the cases, respectively. The study medication was well tolerated. The most frequent adverse events were headache (8.9%) and rhinopharyngitis (7.0%). No unexpected adverse events occurred. CONCLUSIONS: Changing patients' medication from IR-MPH to a single daily dose of OROS-MPH resulted in a significant improvement of ADHD symptoms as rated by parents. In a school setting, the efficacy of OROS-MPH was comparable to that of IR-MPH.

Efficacy, cost-effectiveness, and tolerability of mometasone furoate, levocabastine, and disodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis.

BACKGROUND: Current guidelines recommend intranasal glucocorticosteroids as first-line therapy for seasonal allergic rhinitis. OBJECTIVE: To compare the efficacy, cost-effectiveness, and tolerability of the topical glucocorticosteroid mometasone furoate, the topical antihistamine levocabastine hydrochloride, and the cromone disodium cromoglycate in seasonal allergic rhinitis. METHODS: This study was performed during the 2003 grass pollen season as an open, randomized, parallel-group, single-center study of 123 patients assigned to receive mometasone furoate (200 microg once daily), levocabastine hydrochloride (200 microg twice daily), or disodium cromoglycate (5.6 mg 4 times daily). Symptom scores and nasal inspiratory peak flow measurements were recorded in a patient diary. The global efficacy of the study medication was evaluated by patients after treatment. Eosinophil cationic protein concentrations were measured in nasal secretions before and after treatment. Cost-effectiveness was evaluated as medication cost per treatment success. RESULTS: Mometasone furoate therapy was significantly superior to the use of levocabastine or disodium cromoglycate with respect to all nasal symptoms, the global evaluation of efficacy, and eosinophil cationic protein concentration. Furthermore, mometasone furoate therapy was significantly superior to disodium cromoglycate therapy with respect to nasal inspiratory peak flow. Medication cost per treatment success was lowest with mometasone furoate use and highest with levocabastine use. CONCLUSION: This is the first study to compare mometasone furoate nasal spray with nonsteroidal topical treatments for seasonal allergic rhinitis. Mometasone furoate nasal spray was confirmed as a first-choice topical treatment option for seasonal allergic rhinitis.

Risperidone: an open-label, observational study of the efficacy, tolerability, and prescribing behavior in acutely exacerbated patients with schizophrenia.

OBJECTIVE: Efficacy of atypical antipsychotic in acute schizophrenic episodes is still in debate. This study evaluated treatment practices over 7 years of initial treatment with oral risperidone in acutely exacerbated patients with schizophrenia and in a subgroup of highly agitated, tense, and aggressive patients. Additionally, the study investigated the efficacy and tolerability of risperidone in routine clinical practice. METHODS: In a prospective, multicenter, observational trial from 1996 to 2002, patients with schizophrenia experiencing acute symptom exacerbations were treated with risperidone within 24 hours of inpatient admission. Patients with a total score of > or =15 points on the agitation subscale of the Positive and Negative Syndrome Scale (PANSS) were defined as highly agitated. Efficacy measures were carried out with a modified PANSS, the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS). RESULTS: A total of 1625 patients were evaluated. Despite prescription of decreasing risperidone dosages over 7 years, efficacy was maintained and tolerability improved significantly. Significant symptom relief occurred in all patients and was more pronounced in the subgroup of highly agitated patients (n = 256; P < 0.001 for PANSS, BPRS, and CGI). At Week 6, the mean daily dosage of risperidone was 4.8 mg in the highly agitated patients and 4.7 mg in the remaining patients, and more than 55% of all patients were receiving risperidone as monotherapy. CONCLUSIONS: Prescribing patterns with risperidone in patients with acutely exacerbated schizophrenia, including highly agitated patients, changed with the experience gained with this compound. In routine clinical practice in this indication, risperidone was found to be effective and well tolerated.

Driving ability under long-term treatment with transdermal fentanyl.

Clinical experience shows that neuropsychological side effects due to opioid therapy usually decrease during the first weeks of therapy. However, the effect of long-term treatment with transdermal fentanyl on complex activities, such as driving, is not yet clear. In a prospective trial, patients with continuous noncancer pain, who had received stable doses of transdermal fentanyl for at least 2 weeks, completed a series of computerized tests to measure attention, reaction, visual orientation, motor coordination and vigilance. Data from 90 healthy volunteers were matched to 30 patients; 9 patients were excluded from the per-protocol analysis because they took additional drugs in violation of the protocol. None of the performance measures for the 21 remaining fentanyl patients was significantly inferior to the controls. We conclude that stable doses of transdermal fentanyl for the treatment of chronic non-cancer pain are not associated with significant impairments in psychomotor and cognitive performance. The threshold for fitness to drive as defined by German law did not differ significantly between the groups.