Long-term cardiovascular safety of psychostimulants in children with attention deficit hyperactivity disorder.

Objective: Side effects are a concern during psychostimulant treatment. Unfortunately, many previous studies only investigated short-term effects of psychostimulants in laboratory settings which lack clinical daily routines. Methods: We examined 1042 patient records of patients with attention deficit hyperactivity disorder (ADHD) who were referred to a pediatric-psychiatry practice over 12 years. Data analysis was based on 466 children with ADHD who were newly treated with psychostimulants and who were not in treatment for elevated blood pressure. We analysed blood pressure percentiles, heart rate and BMI percentiles. Results: There was a decrease in systolic and diastolic blood pressure percentiles. Heart rate was not affected. BMI slightly declined in girls. Conclusions: In general psychostimulants were safe. To further elucidate negative effects of psychostimulants, long-term controlled and randomized studies in naturalistic settings are of interest.

Pediatric psychopharmacological research in the post EU regulation 1901/2006 era.

Although the use of psychotropic medications in child and adolescent psychiatry in Germany is on the increase, most compounds are in fact prescribed "off-label" because of a lack of regulatory approval in these age groups. In 2007, the European Parliament introduced Regulation 1901/2006 concerning medicinal products in pediatric populations, with a subsequent amendment in the form of Regulation 1902/2006. The main aim of this legislation was to encourage research and clinical trials in children and adolescents, and thus promote the availability of medications with marketing authorization for these age groups. Furthermore, initiatives such as the European 7th Framework Program of the European Union now offer substantial funding for pediatric pharmacological research. At a recent Congress of the German Society for Child and Adolescent Psychiatry and Psychotherapy (DGKJP), experts from the field and the pharmaceutical industry held a symposium with lay representatives in order to discuss attitudes toward, and experience with, pediatric psychopharmacology research in Germany since 2007. Several areas of concern were identified. The present paper derives from that symposium and provides an overview of these opinions, which remain crucial to the field. A wider discussion of how to facilitate psychopharmacological research in Germany in order to optimize the treatment and welfare of children and adolescents with psychiatric disorders is now warranted.

Long-term efficacy and safety outcomes with OROS-MPH in adults with ADHD.

Methylphenidate (MPH) is widely prescribed for adults with attention deficit hyperactivity disorder (ADHD), but data on long-term treatment and maintenance of effect are lacking. Osmotic release oral system-methylphenidate (OROS-MPH) was evaluated in a 52-wk open-label study in subjects who had previously completed a short-term placebo-controlled trial and short-term open-label extension. Efficacy was assessed using the investigator- and subject-rated Conners' Adult ADHD Rating Scales (CAARS:O-SV and CAARS:S-S), and the Clinical Global Impression - Severity (CGI-S), Sheehan Disability Scale (SDS) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Subjects completing ≥52 wk of treatment were eligible for a 4-wk randomized, placebo-controlled withdrawal phase in which loss of treatment effect was assessed using CAARS:O-SV and CGI-S. In the open-label phase (n=156), mean CAARS:O-SV score decreased from baseline by 1.9±7.8 (p<0.01), and small, statistically significant improvements from baseline were observed for CAARS:S-S, CGI-S and SDS. In the double-blind phase (OROS-MPH, n=23; placebo, n=22), CAARS:O-SV increased from double-blind baseline in the OROS-MPH and placebo arms (4.0±7.6 vs. 6.5±7.8, not statistically significant). Long-term OROS-MPH treatment was well tolerated, and there was no evidence of withdrawal or rebound after discontinuation. In conclusion, the short-term benefits of OROS-MPH continue during long-term open-label treatment. Maintenance of efficacy in a placebo-controlled withdrawal design remains to be confirmed in larger patient populations.

[Children with attention deficit hyperactivity disorder in school]. / Medikamente, Verhaltenstherapie, Allgemeinmassnahmen. Hilfen für ADHS-kinder.

To keep secondary disorders to a minimum, the early diagnosis and treatment of ADHD and its possible comorbidities is important. Aside from the care of a specialist, several additional measures permit the integration of these children into a structured everyday school routine and thus also permit age-appropriate development.

[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.

A randomized, placebo-controlled trial of three fixed dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: There is increasing recognition of attention-deficit/hyperactivity disorder (ADHD) in adults and the need to evaluate efficacy and safety of methylphenidate treatment in these patients. METHODS: In this double-blind trial, 401 adults with ADHD (218 men; 18-63 years) were randomly assigned to receive prolonged-release osmotic release oral system (OROS) methylphenidate (18 mg, 36 mg, or 72 mg/day) or placebo for 5 weeks. Primary outcome was change in total score on Conners' Adult ADHD Rating Scale (CAARS: investigator-rated) at end point compared with baseline. Adverse events, vital signs, and laboratory parameters were assessed. RESULTS: Treatment with 18-mg, 36-mg, and 72-mg/day prolonged-release methylphenidate, compared with placebo, was associated with significantly larger improvement in CAARS total symptom score from baseline to end point than placebo: mean change -10.6 (p = .01), -11.5 (p = .01), and -13.7 (p < .001) versus -7.6, respectively. Responders (> or = 30% decrease) were 50.5%, 48.5%, and 59.6% versus 27.4% (p < .001). Other efficacy measures also showed improvements. Incidence of adverse events was 75%, 76%, and 82% in 18-mg, 36-mg, and 72-mg/day groups, respectively, and 66% in placebo; most frequent included decreased appetite (25% methylphenidate; 7% placebo) and headache (21% methylphenidate; 18% placebo). In methylphenidate-treated patients, 4.3% discontinued due to adverse event; one serious adverse event was possibly related to study drug. Blood pressure and pulse increased at week 1 and then remained stable through week 5. CONCLUSIONS: Prolonged-release methylphenidate is an effective treatment of ADHD in adults, with a safety profile consistent with methylphenidate use in pediatrics.

Attention-deficit/hyperactivity disorder (ADHD) in the course of life.

ADHD is a pervasive disorder that extensively impairs the quality of life and that can lead to serious secondary problems. Contrary to the prior assumption long-term studies have demonstrated that the disorder is not limited to childhood and adolescence. Unfortunately appropriate criteria for adults with ADHD are not given in the ICD-10. The clinical experience indicates substantial difficulties of adults, whose ADHS is not diagnosed and treated. They often cause extensive costs for the welfare system. The evidence-based psychiatric treatment is highly effective and inexpensive.