Characterizing non-OCD anxiety disorders in psychiatrically referred children and adolescents.

BACKGROUND: To characterize childhood and adolescent anxiety disorders in a psychiatric clinic. METHODS: Subjects were 1375 youth referred to a pediatric psychopharmacology program at a major academic center from 1991-2002. DSM-III-R diagnoses were obtained by Schedule for Affective Disorders and Schizophrenia for School-Age Children. RESULTS: Of 1375 referred youth, 794 had at least one non-obsessive-compulsive anxiety disorder, and 581 psychiatric comparison subjects had at least one disruptive behavior disorder and no anxiety disorders. There were 367 (46%) youth with one anxiety disorder, 224 (28%) with two disorders. Most prevalent were separation anxiety (49%), and overanxious disorder (47%). Mean ages of onset ranged from simple phobia (4.1) to panic disorder (8.5). Risk analyses revealed anxiety disorders significantly increased risk for anxiety and mood disorders. CONCLUSIONS: The full complement of anxiety disorders occurs in youth.

Is oppositional defiant disorder a meaningful diagnosis in adults? Results from a large sample of adults with ADHD.

We examined the prevalence and clinical characteristics of oppositional defiant disorder (ODD) in a sample of clinically referred adults with attention deficit hyperactivity disorder (ADHD). Subjects were consecutively referred adults with a DSM-III R/IV diagnosis of ADHD with or without ODD. Nearly half of subjects (43%) had a history of ODD. Subjects with a childhood history of ODD had increased risk for bipolar disorder, multiple anxiety disorders, and substance use disorders relative to the ADHD subjects without ODD. We concluded, as in children with ODD, adults with a childhood history of ODD have high rates of psychiatric comorbidity and more impaired psychosocial functioning than those without this condition. A better understanding of the course, phenomenology, and clinical significance of ODD in adults is needed to better understand therapeutic approaches for this disorder.

A double-blind comparison of galantamine hydrogen bromide and placebo in adults with attention-deficit/hyperactivity disorder: a pilot study.

BACKGROUND: Galantamine hydrogen bromide (HBr) is a competitive and reversible inhibitor of acetylcholinesterase. Because of its cholinergic nicotinic mechanism of action, galantamine HBr was hypothesized to have therapeutic activity in the treatment of attention-deficit/hyperactivity disorder (ADHD). METHOD: We conducted a 12-week, double-blind, placebo-controlled, randomized clinical trial using daily doses of up to 24 mg/d of galantamine HBr in the treatment of adults who met full Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD with childhood-onset and persistent adult symptoms. All analyses were intention to treat with the last observation carried forward for subjects who did not complete the full study schedule. RESULTS: The mean daily doses at week 12 were 19.8 +/- 6.4 mg for galantamine HBr and 21.8 +/- 4.6 mg for placebo (P = 0.3). There was no statistically or clinically significant greater reduction in ADHD symptoms in subjects treated with galantamine HBr relative to those receiving placebo (P = 0.5). Using last observation carried forward, 4 (22%) of 18 of patients receiving galantamine HBr were considered responders (much or very much improved on the Clinical Global Impression Improvement Scale and at least a 30% reduction on the ADHD Investigator Symptom Report Scale compared with 11% [2/18] on placebo; P = 0.4). CONCLUSION: These results do not support the clinical utility of galantamine HBr in the treatment of ADHD at the doses used in this pilot study.

A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of once-daily OROS methylphenidate (MPH) in the treatment of adults with DSM-IV attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a randomized, 6-week, placebo-controlled, parallel-design study of OROS MPH in 141 adult subjects with DSM-IV ADHD, using standardized instruments for diagnosis. OROS MPH or placebo was initiated at 36 mg/day and titrated to optimal response, depending on efficacy and tolerability, up to 1.3 mg/kg/day. RESULTS: Treatment with OROS MPH was associated with clinically and statistically significant reductions in DSM-IV symptoms of inattention and hyperactivity/impulsivity relative to subjects treated with placebo. At endpoint, 66% of subjects (n = 44) receiving OROS MPH and 39% of subjects (n = 29) [corrected] receiving placebo attained our a priori definition of response of much or very much improved on the Clinical Global Impression-Improvement scale plus a >30% reduction in Adult ADHD Investigator System Report Scale score. OROS MPH was associated with small but statistically significant increases in systolic blood pressure (3.5 +/- 11.8 mm Hg), diastolic blood pressure (4.0 +/- 8.5 mm Hg), and heart rate (4.5 +/- 10.5 bpm). CONCLUSIONS: These results show that treatment with OROS MPH in daily doses of up to 1.3 mg/kg/day was effective in the treatment of adults with ADHD. Because of the potential for increases in blood pressure and heart rate, subjects receiving treatment with MPH should be monitored for changes in blood pressure parameters during treatment.

Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children.

BACKGROUND: To evaluate short-term safety and efficacy of atypical antipsychotics in a single-site, prospective, open-label, 8-week study of risperidone and olanzapine monotherapy in preschoolers with bipolar disorder (BPD). METHODS: Risperidone was initiated at an open-label dose of .25 mg/day, increased weekly according to response and tolerability to a maximum does of 2.0 mg/day. Olanzapine was initiated at 1.25 mg/day and increased to no more than 10 mg/day. RESULTS: Thirty-one children aged 4-6 years were treated with olanzapine (n = 15, 6.3 +/- 2.3 mg/day) or risperidone (n = 16, 1.4 +/- .5 mg/day). At study end point (week 8 or last observation carried forward), there was a 18.3 +/- 11.9 point (t = -5.6, p < .001) reduction in risperidone-treated subjects and a 12.1 +/- 10.4 point (t = -4.4, p < .001) reduction in Young Mania Rating Scale (YMRS) scores in olanzapine-treated subjects that did not differ between groups (t = 1.4, p = .2). Response criteria (Clinical Global Impression improvement of "Much" or "Very Much" improved or a YMRS change of >or= 30% or more) indicated no difference in rate of response with risperidone and olanzapine (69% vs. 53%, chi(2)((1)) = .8, p = .4). CONCLUSIONS: This prospective open study suggests that treatment with risperidone or olanzapine may result in a rapid reduction of symptoms of mania in preschool children with BPD. Because of substantial residual symptomatology and adverse effects, however, a pressing need exists to identify additional safe and effective treatments for the management of BPD in this high-risk population.