Jeff Q. Bostic

Bupropion Sustained Release in Adolescents With Comorbid Attention-Deficit/Hyperactivity Disorder and Depression

OBJECTIVEnTo determine whether bupropion sustained release (SR) is effective and well-tolerated in adolescents with comorbid attention-deficit/hyperactivity disorder (ADHD) and depression.nnnMETHODnSubjects were 24 adolescents (aged 11-16 years old) with ADHD and either major depressive disorder or dysthymic disorder. After a 2-week, single-blind placebo lead-in, subjects were treated for 8+ weeks with bupropion SR at doses flexibly titrated up to 3 mg/kg b.i.d. (mean final doses: 2.2 mg/kg q A.M. and 1.7 mg/kg q P.M.). Outcomes were global improvement in ADHD and depression (clinician-rated), along with changes in depressive symptomatology (parent- and child-rated), ADHD symptomatology (parent- and teacher-rated), and functional impairment (parent-rated).nnnRESULTSnClinicians rated 14 subjects (58%) responders in both depression and ADHD, 7 (29%) responders in depression only, and 1 (4%) a responder in ADHD only. Compared with post-placebo ratings, final parents (p < .0005) and childrens (p = .016) ratings of depressive symptomatology improved significantly, as did parents (p < .0005) but not teachers (p = .080) ratings of ADHD symptomatology. Final ratings of functional impairment improved significantly from enrollment (p < .0005). No subject discontinued medication because of side effects.nnnCONCLUSIONSnBupropion SR may be effective and well-tolerated in adolescents with comorbid ADHD and depressive disorders. However, randomized, placebo-controlled studies are needed.

Improving Access to Mental Health Care for Children: The Massachusetts Child Psychiatry Access Project

BACKGROUND: Inadequate access to care for mentally ill children and their families is a persistent problem in the United States. Although promotion of pediatric primary care clinicians (PCCs) in detection, management, and coordination of child mental health care is a strategy for improving access, limitations in training, time, and specialist availability represent substantial barriers. The Massachusetts Child Psychiatry Access Project (MCPAP), publicly funded with 6 regional consultation teams, provides Massachusetts PCCs with rapid access to child psychiatry expertise, education, and referral assistance. METHODS: Data collected from MCPAP teams measured participation and utilization over 3.5 years from July 1, 2005, to December 31, 2008. Data were analyzed for 35 335 encounters. PCC surveys assessed satisfaction and impact on access to care. RESULTS: The MCPAP enrolled 1341 PCCs in 353 practices covering 95% of the youth in Massachusetts. The MCPAP served 10 114 children. Practices varied in their utilization of the MCPAP, with a mean of 12 encounters per practice per quarter (range: 0–245). PCCs contacted the MCPAP for diagnostic questions (34%), identifying community resources (27%), and consultation regarding medication (27%). Provider surveys revealed improvement in ratings of access to child psychiatry. The rate of PCCs who reported that they are usually able to meet the needs of psychiatric patients increased from 8% to 63%. Consultations were reported to be helpful by 91% of PCCs. CONCLUSIONS: PCCs have used and value a statewide system that provides access to teams of psychiatric consultants. Access to child mental health care may be substantially improved through public health interventions that promote collaboration between PCCs and child mental health specialists.

Use of citalopram in pervasive developmental disorders.

ABSTRACT. This study assessed the effectiveness and tolerability of the selective serotonin reuptake inhibitor citalopram in the treatment of patients with pervasive developmental disorders (PDDs). The medical charts of 15 children and adolescents (aged 6–16 yr) with Asperger syndrome, autism, or PDD not otherwise specified treated with citalopram were retrospectively reviewed. The final dose of citalopram was 16.9 ± 12.1 mg/day with a treatment duration of 218.8 ± 167.2 days. Independent ratings of the Clinical Global Impression (CGI) Severity and Improvement scales allowed comparison between baseline and PDD symptoms at the last visit. Eleven adolescents (73%) exhibited significant improvement in PDD, anxiety, or mood CGI score (z = 2.95;p = .003). Anxiety symptoms associated with PDDs improved significantly in 66% of patients (z = 2.83, p = .005), and mood symptoms improved significantly in 47% of patients (z = 2.78, p = .005). Mild side effects were reported by five patients (33%). These data suggest citalopram may be effective, safe, and well tolerated as part of the treatment of PDDs.

A Controlled Study of Nortriptyline in Children and Adolescents with Attention Deficit Hyperactivity Disorder

OBJECTIVESnTo study the efficacy and tolerability of nortriptyline (NT) in the treatment of pediatric attention deficit hyperactivity disorder (ADHD).nnnMETHODOLOGYnSubjects were outpatient children and adolescents with ADHD ascertained from clinical referrals. Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks. Using either a 30 % reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression (CGI) scale for ADHD improvement, responders to treatment were then randomized into a 3-week, controlled discontinuation phase. During this phase, subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions. Subjects were monitored for symptoms of ADHD, oppositionality, anxiety, and depression.nnnRESULTSnOf the 35 subjects enrolled in the study, 32 completed the open phase and 23 completed the discontinuation phase. The mean dose of NT was 80 mg (1.8 mg/kg/day), resulting in a serum level of 81 ng/ml. At the conclusion of the open 6-week study, NT was related to a significant reduction in ADHD (p < 0.001) and oppositional symptoms (p < 0.001). At the conclusion of the discontinuation phase, the 12 subjects randomized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects randomized to placebo (31 versus 21; t = 2.2; p < 0.04). No significant adverse events were observed, and children were noted to have weight gain during the trial.nnnCONCLUSIONSnThese data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality. This group of children and adolescents tolerated robust dosing of NT well, with few clinical or cardiovascular adverse events.

Controlled trial of high doses of pemoline for adults with attention-deficit/hyperactivity disorder

Despite the increasing awareness of attention-deficit/hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder. Because the stimulant medication magnesium pemoline (Cylert, Abbott Laboratories, Abbott Park, IL) has been found effective in treating ADHD in pediatric groups, we tested its efficacy in adults with ADHD using higher daily doses than those previously studied. We conducted a 10-week, double-blind, placebo-controlled, crossover design study of pemoline at a target daily dose of 3 mg/kg per day in 35 adult patients with DSM-III-R and -IV ADHD. We used standardized structured psychiatric instruments for diagnosis. To measure improvement, we used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. ADHD outcome was determined using the ADHD symptom checklist and Clinical Global Impression scales of Severity and Improvement. Of the 35 adults with ADHD who were randomized in the trial, 27 (77%) completed the protocol. Treatment with pemoline in the final week of the 4-week active phase was best tolerated at doses substantially lower than the target dose of 3 mg/kg per day (mean dose, 2.2 mg/kg per day; mean+/-SD, 148+/-95 mg). Pemoline was significantly better at reducing ADHD symptoms compared with placebo (z = 2.4,p < 0.02). Using a predefined 30% reduction in symptoms as an indication of improvement, 50% of pemoline-treated subjects and 17% of subjects in the placebo group were considered positive responders (chi2 = 7.1, p = 0.008). These results indicate that pemoline is moderately effective in the treatment of ADHD in adults. Although robust doses were targeted, most adults preferred more moderate dosing (120-160 mg/day). Given the limited efficacy, tolerability, and concerns of hepatic dysfunction, pemoline should be considered as second-line medication for treating ADHD in adults.

Pemoline Treatment of Adolescents with Attention Deficit Hyperactivity Disorder: A Short-Term Controlled Trial

BACKGROUNDnDespite the increased recognition of attention deficit hyperactivity disorder (ADHD) in adolescents, few controlled studies have assessed treatments for this age group. Adolescent issues, such as embarrassment at receiving medication at school and experimentation with abusable substances, have accelerated efforts to find effective, well-tolerated treatments beyond traditional stimulants. Pemoline has been found effective for treating both children and adults with ADHD but has not been evaluated in adolescents with ADHD.nnnMETHODSnTwenty-one adolescents (mean age 14 years old) diagnosed with ADHD by structured and clinical interviews participated in a 10-week, double-blind crossover design study of pemoline. Dosing was optimized with robust doses up to 3 mg/kg/day in one to two doses. Clinical evaluations of ADHD, depression, anxiety, and oppositional defiant disorder (ODD) symptoms were assessed weekly.nnnRESULTSnAdolescents with ADHD exhibited a marked response to pemoline treatment relative to placebo on the ADHD rating scale (p = 0.001), with an average reduction of 3.02 points per week of treatment. Sixty percent of adolescents responded to pemoline, compared to 11% treated with placebo. This response was independent of gender or lifetime psychiatric comorbidity. Pemoline was well tolerated, with patients averaging 2.88 mg/kg/day in two doses per day, with a mean dose at end of follow-up of 181.1 mg (SD 45.6, range 112.5-262.5 mg). Side effects were mild, and no adverse hepatic events occurred.nnnCONCLUSIONSnThese findings resemble those reported in children and adults with ADHD. This trial suggests pemoline is well tolerated and effective in adolescents and may be a particularly useful ADHD treatment for adolescents.

Treatment of depression in children and adolescents.

Depression occurs in children and adolescents, although it may appear differently in younger patients. Research suggests juvenile depression may respond to psychotherapy and to pharmacologic agents, and that antidepressants remain a valuable treatment for juveniles with depression. Diagnostic considerations in juveniles with mood symptoms are discussed. A brief overview is provided of the evidence supporting psychotherapy for juveniles with depression. Controlled antidepressant trials in juveniles with depression provide some support for the use of some selective serotonin reuptake inhibitors and little support for atypical antidepressants, tricyclic antidepressants, or monoamine oxidase inhibitors. Evidence from suicide rates over time, autopsy findings among juvenile suicides, and impacts of antidepressant prescribing trends are related to the current controversy over suicidality and antidepressant use in juvenile patients. Based on this evidence, practical guidelines for treatment of juvenile depression are provided.

A Retrospective Study of Citalopram in Adolescents with Depression

Recent evidence suggests that the selective serotonin reuptake inhibitors are safe and efficacious in treating juveniles with depression. However, citalopram has not been reported in adolescents with depression. This study assessed the effectiveness and tolerability of citalopram in all adolescents with depressive disorders treated naturalistically in a community mental health center during a 1-year interval. Medical charts were retrospectively reviewed for 21 adolescents treated with citalopram for major depression (n = 14), bipolar depression (n = 4), or dysthymia (n = 3). An independent rater compared last visit to baseline depression using the Clinical Global Impression (CGI) Severity and Improvement scales. Adolescents received citalopram for an average of 128.5 +/- 84 days at a final average dose of 26.5 +/- 13.1 mg/day. Sixteen of these 21 adolescents (76%) exhibited much to very much improvement as measured by the CGI, and severity of depression diminished significantly (z = 3.007, p < 0.0026). Mild side effects, including headaches, dizziness, nausea, sedation, agitation, and sweating were reported by 7 (33%) of the patients. These data suggest that citalopram may be effective, safe, and well tolerated in the treatment of adolescents with depressive disorders and that controlled trials are warranted in this population.

The relationship between childhood asthma and Attention Deficit Hyperactivity Disorder: A review of the literature

Objective(s): To clarify any etiological or symptomatic relationship between asthma and Attention Deficit Hyperactivity Disorder (ADHD). Study Design: A systematic review of the literature was conducted through Medline. Results: We found little evidence of an over- representation of ADHD, academic, or behavioral problems in asthmatic children or of asthma among children with ADHD. We also failed to find convincing evidence that the standard treatment of asthma causes ADHD-like symptoms or academic decline in asthmatic children. Conclusion: These findings indicate that asthmatic children with school or behavioral problems may also suffer from ADHD and require treatment for both disorders.

JUVENILE MOOD DISORDERS AND OFFICE PSYCHOPHARMACOLOGY

Mood disorders afflict pediatric patients, cause significant impairment, and interfere with normal development. Increasingly, pediatricians are called on to assess and collaborate with mental health practitioners in medicating children and adolescents with mood disorders. Approaching the juvenile with a primary emphasis on clarifying the diagnoses, determining environmental antecedents and sequelae, and investigating suicide risk enables the pediatrician to institute appropriate treatment. Despite limited data from controlled studies, psychotherapy often is used for mild to moderate depression. Pharmacotherapy is indicated in cases unresponsive to psychotherapy and in severe or suicidal cases. First-line pharmacotherapy for depressed adolescents is usually an SRI followed by the atypical or TCA antidepressants. Bipolar disorder typically requires an aggressive medication regimen, including anticonvulsants, lithium, or a combination, as well as environmental modifications. With severe, difficult, or refractory cases, mental health consultation is recommended to clarify diagnoses and to provide psychotherapy and medication input.