Journal of Child and Adolescent Psychopharmacology

This case report represents the first example of treatment strategy of antipsychotic-induced dyslipidemia in children, on the basis of evidence that omega 3 is effective in the treatment of dyslipidemia in general medicine (Balk et al. 2006). Although considering all limitations of a single case report, the degree of reduction of TC, LDL, and TG, as well as the increase of HDL, the long period of follow-up and the stopping– reintroducing strategy provide some evidence of the direct effect of omega 3 supplement ...

This study examined subjective and other behavioral effects of methylphenidate (MPH) among adolescents. Standard abuse liability assessment methods that have been used in adult populations were modified for attention-deficit/hyperactivity disorder (ADHD) adolescents. MPH effects (0, 0.25 mg/kg) were evaluated under randomized, double-blind conditions in two 5-hour laboratory sessions in 24 (13 female) 11-15 year olds diagnosed with ADHD. Repeated measures analysis of covariance indicated significant dose and dose by time interactions on subjective ratings on the modified amphetamine (A) [F (1, 20) = 5.98; p < 0.05; eta2 = 0.36], morphine-benzedrine group (MBG) [F (1, 21) = 8.93 p < 0.01; eta2 = 0.38] and benzedrine group scale (BG) [F (1, 21) + 13.10 p < 0.01; eta2 = 0.37] scales of the Addiction Research Center Inventory; "Hungry" and "How sure are you that you got the medication today?" from the Visual Analogue Scale, the Profile of Mood States Depression scale, performance on the Continuous Performance Task, heart rate and blood pressure, and level of activity. This is the first study to document subjective effects of stimulants in adolescents with ADHD that have been associated with drug abuse potential in adults. There are increasing concerns about nontherapeutic stimulant use in adolescents and young adults. Assessing subjective effects of pharmacotherapies for ADHD along with other measures of abuse potential such as drug self-administration may aid in assessing the therapeutic effects and/or risk of medications used in the treatment of ADHD.

Risperidone has been shown to improve serious behavioral problems in children with autism. Here we asked whether risperidone-associated improvement was related to changes in concentrations of inflammatory molecules in the serum of these subjects. Seven molecules were identified as worthy of further assessment by performing a pilot analysis of 31 inflammatory markers in 21 medication-free subjects with autism versus 15 healthy controls: epidermal growth factor (EGF), interferon-γ (IFN-γ), interleukin (IL)-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), IL-1 and IL-1-receptor antagonist. Serum concentrations of these markers were then established in a different set of subjects that participated in a double-blind, clinical trial and an expanded group of healthy subjects. In the first analysis, samples obtained from subjects with autism at baseline visits were compared to visits after 8-week treatment with placebo (n=37) or risperidone (n=40). The cytokine concentrations remained stable over the 8-week period for both risperidone and placebo groups. In the second analysis, we explored further the differences between medication-free subjects with autism (n=77) and healthy controls (recruited independently; n=19). Serum levels of EGF were elevated in subjects with autism (median=103 pg/mL, n=75) in comparison to healthy controls (75 pg/mL, n=19; p<0.05), and levels of IL-13 were decreased in autism (median=0.8 pg/mL, n=77) in comparison to controls (9.8 pg/mL, n=19; p=0.0003). These changes did not correlate with standardized measures used for a diagnosis of autism. In summary, risperidone-induced clinical improvement in subjects with autism was not associated with changes in the serum inflammatory markers measured. Whether altered levels of EGF and IL-13 play a role in the pathogenesis or phenotype of autism requires further investigation.

The aim of this study was to determine the effectiveness and tolerability of aripiprazole for irritability in pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger's disorder. This is a 14-week, prospective, open-label investigation of aripiprazole in 25 children and adolescents diagnosed with PDD-NOS or Asperger's disorder. Primary outcome measures included the Clinical Global Impressions-Improvement (CGI-I) scale and the Irritability subscale of the Aberrant Behavior Checklist (ABC-I). Twenty-five subjects, ages 5-17 years (mean 8.6 years) received a mean final aripiprazole dosage of 7.8 mg/day (range 2.5-15 mg/day). Full-scale intelligence quotient (IQ) scores ranged from 48 to 122 (mean 84). Twenty-two (88%) of 25 subjects were responders in regard to interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-I of 1 or 2 (very much or much improved) and a 25% or greater improvement on the ABC-I. The final mean CGI-I was 1.6 (p <or= 0.0001). ABC-I scores ranged from 18 to 43 (mean 29) at baseline, whereas scores at week 14 ranged from 0 to 27 (mean 8.1) (p <or= 0.001). Aripiprazole was well tolerated. Mild extrapyramidal symptoms (EPS) were reported in 9 subjects. Age- and sex-normed body mass index (BMI) increased from a mean value of 20.3 at baseline to 21.1 at end point (p <or= 0.04). Prolactin significantly decreased from a mean value of 9.3 at baseline to 2.9 at end point (p <or= 0.0001). No subject exited the study due to a drug-related adverse event. These preliminary data suggest that aripiprazole may be effective and well tolerated for severe irritability in pediatric patients with PDD-NOS or Asperger's disorder. Larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of aripiprazole in this understudied population.

Objective: The purpose of this study was to evaluate atomoxetine treatment effects in attention-deficit/hyperactivity disorder (ADHD-only), attention-deficit/hyperactivity disorder with comorbid dyslexia (ADHD+D), or dyslexia only on ADHD core symptoms and on sluggish cognitive tempo (SCT), working memory, life performance, and self-concept. Methods: Children and adolescents (10-16 years of age) with ADHD+D (n=124), dyslexia-only (n=58), or ADHD-only (n=27) received atomoxetine (1.0-1.4 mg/kg/day) or placebo (ADHD-only subjects received atomoxetine) in a 16 week, acute, randomized, double-blind trial with a 16 week, open-label extension phase (atomoxetine treatment only). Changes from baseline were assessed to weeks 16 and 32 in ADHD Rating Scale-IV-Parent-Version:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv); ADHD Rating Scale-IV-Teacher-Version (ADHDRS-IV-Teacher-Version); Life Participation Scale-Child- or Parent-Rated Version (LPS); Kiddie-Sluggish Cognitive Tempo (K-SCT) Interview; Multidimensional Self Concept Scale (MSCS); and Working Memory Test Battery for Children (WMTB-C). Results: At week 16, atomoxetine treatment resulted in significant (p<0.05) improvement from baseline in subjects with ADHD+D versus placebo on ADHDRS-IV-Parent:Inv Total (primary outcome) and subscales, ADHDRS-IV-Teacher-Version Inattentive subscale, K-SCT Interview Parent and Teacher subscales, and WMTB-C Central Executive component scores; in subjects with Dyslexia-only, atomoxetine versus placebo significantly improved K-SCT Youth subscale scores from baseline. At Week 32, atomoxetine-treated ADHD+D subjects significantly improved from baseline on all measures except MSCS Family subscale and WMTB-C Central Executive and Visuo-spatial Sketchpad component scores. The atomoxetine-treated dyslexia-only subjects significantly improved from baseline to week 32 on ADHDRS-IV-Parent:Inv Inattentive subscale, K-SCT Parent and Teacher subscales, and WMTB-C Phonological Loop and Central Executive component scores. The atomoxetine-treated ADHD-only subjects significantly improved from baseline to Week 32 on ADHDRS-Parent:Inv Total and subscales, ADHDRS-IV-Teacher-Version Hyperactive/Impulsive subscale, LPS Self-Control and Total, all K-SCT subscales, and MSCS Academic and Competence subscale scores. Conclusions: Atomoxetine treatment improved ADHD symptoms in subjects with ADHD+D and ADHD-only, but not in subjects with dyslexia-only without ADHD. This is the first study to report significant effects of any medication on SCT. Clinical trials registration: This study was registered at: http://clinicaltrials.gov/ct2/home, NCT00607919.

This study investigated the psychometric properties of a new clinician-rated scale designed to assess the severity of social phobia and measure treatment outcome in adolescents: the Kutcher Generalized Social Anxiety Disorder Scale for Adolescents (K-GSADS-A). Two hundred fifty-one (251) adolescents (11-17 years; mean age 14.2 years) with DSM-IV social phobia enrolled in a multicenter, 16-week, double-blind, placebo-controlled study of paroxetine. Efficacy assessments were conducted at baseline and at weeks 4, 8, 12, and 16 with the K-GSADS-A, three other clinician-rated scales (including the Clinical Global Impression of Severity scale), and a self-rated social phobia scale. Additionally, the Clinical Global Impression of Improvement scale was administered at each postbaseline assessment, and the Children's Depression Rating Scale-Revised was administered at baseline and at week 16. These data were used to assess the internal consistency, convergent and divergent validity, and sensitivity to change of the K-GSADS-A. The internal consistency of the K-GSADS-A was adequate, and supportive evidence was obtained for its convergent validity with other severity measures, and its divergent validity with respect to depression. The K-GSADS-A also demonstrated good sensitivity to changes in severity. These results suggest that the K-GSADS-A is a valid measure of treatment outcome in adolescents with DSM-IV social phobia.

To report the long-term efficacy of aripiprazole in the treatment of irritability in children and adolescents (ages 6-17 years) with autistic disorder. This was a 52-week, open-label, flexible-dose (2-15 mg/day) study of aripiprazole for the treatment of children and adolescents with irritability associated with autistic disorder. Eligible subjects were enrolled from two 8-week randomized trials or were enrolled as de novo subjects. "Prior aripiprazole" subjects had received treatment with aripiprazole for 8 weeks before entering this study. Evaluation of efficacy, a secondary objective after evaluation of safety and tolerability in this study, was conducted using the caregiver-rated Aberrant Behavior Checklist-Irritability subscale and the clinician-rated Clinical Global Impression-Improvement score. Three hundred thirty subjects received treatment (de novo, n = 86; prior aripiprazole, n = 174; prior placebo, n = 70) and 199 subjects (60.3%) completed 52 weeks of treatment. At their last study visit, 38.2% of subjects were receiving concomitant central nervous system medications (commonly antidepressants, 13.4%; psychostimulants, 11.5%; antiepileptics, 5.9%). At week 52 (observed cases data set), the mean change from baseline in Aberrant Behavior Checklist Irritability subscale scores was -8.0 in de novo subjects and -6.1 in prior placebo subjects; prior aripiprazole subjects maintained symptom improvement that was achieved with treatment in the prior study. At endpoint, the majority of subjects had a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved). Aripiprazole reduced symptoms of irritability associated with autistic disorder in pediatric subjects ages 6-17 years who were studied for up to 1 year.

In a sample of 40 youths (ages 11-17) with obsessive-compulsive disorder (OCD) and mood disorders who were treated with behavior therapy, 20 patients received serotonin reuptake inhibitors (SRIs) and 20 did not. In open-label clinical treatment, 30% of the patients (6/20) treated with SRIs developed manic or hypomanic symptoms (5/15 on fluoxetine, 1/1 on sertraline). Symptoms included impulsivity, grandiosity, pressured speech, and disinhibition and did not resemble akathisia or "behavioral activation." These behaviors emerged despite gradual dose elevation (2-5 mg/wk), conservative dosing (maximum 40 mg daily), and careful weekly outpatient monitoring of each patient. Fluoxetine-induced mania occurred at doses as low as 10 mg daily. It is unclear whether mania/hypomania would appear in OCD children without comorbid mood disorders or, alternatively, whether OCD is a stronger risk factor than mood disorder for manic switch in SRI-treated youths. Clinicians are advised to be aware of the risk and to be vigilant in monitoring manic and hypomanic behaviors when using SRIs to treat OCD in youth, even with low doses and gradual dose elevation.

Olanzapine is an atypical antipsychotic medication that was approved for use in the United States in 1996. While it is a widely used medication in adults, there has been minimal investigation into its effect on children. We present the case of an 18-month-old boy who ingested 30-40 mg of olanzapine, which resulted in significant symptoms, including respiratory distress and mental status changes. Previously reported pediatric cases of olanzapine ingestion have described similar symptoms. Therefore, the pediatric population should be monitored closely when ingestions of olanzapine occur.

Objective: The aim of this study was to assess the use of atomoxetine and olanzapine in combination to treat attention-deficit/hyperactivity disorder (ADHD) and comorbid disruptive behaviors in children and adolescents 10-18 years of age. Methods: Eleven subjects ages 10-18 received open-label atomoxetine and olanzapine for a 10 week treatment period. Patients were assessed at baseline, 2 weeks, 4 weeks, 6 weeks, and 10 weeks (posttreatment). ADHD improvement was measured through the ADHD Rating Scale (ADHD-RS) (Investigator and Parent ratings). Aggression was measured through the Modified Overt Aggression Scale (MOAS). Results: The combined use of atomoxetine and olanzapine resulted in statistically significant improvement in ADHD symptoms and overt aggression from baseline to posttreatment. As evidenced by a 33% reduction in symptoms on the ADHD-RS-I and the MOAS, 73% of patients were considered responders to ADHD treatment, whereas 55% responded to treatment for aggression. Both medications were generally well tolerated. Olanzapine treatment was associated with significant weight gain. Patients gained, on average, 3.9 kg. throughout the treatment period. Conclusions: These data provide initial evidence that combination use of atomoxetine and olanzapine for the treatment of ADHD and comorbid disruptive behaviors was effective in reducing ADHD symptoms and aggressive behavior in a 10 week treatment period.

We present a brief historical overview of the prevalence studies of psychotropic drugs in individuals with mental retardation that were published between 1966 and 1985, and a more comprehensive review of the prevalence studies from 1986 to 1995. During the 1966 to 1985 period, typical prevalence rates of drug treatments in institutions (children and adults analyzed together) were found to range from 30% to 40% for psychotropic drugs, 25% to 45% for anticonvulsants, and 50% to 70% for psychotropic and/or anticonvulsant drugs (i.e., psychotropics, anticonvulsants, or their combinations). In the community during the same period, prevalence rates in children were typically 2% to 7% for psychotropics, 12% to 31% for anticonvulsants, and 18% to 33% for psychotropic and/or anticonvulsant drugs. For adults in the community, prevalence rates ranged from 26% to 36% for psychotropics, 18% to 24% for anticonvulsants, and 36% to 48% for psychotropic and/or anticonvulsant drugs. In contrast, during the 1986 to 1995 period, typical prevalence rates in institutions ranged from 12% to 40% for psychotropics, 24% to 41% for anticonvulsants, and 44% to 60% for psychotropic and/or anticonvulsant drugs. In the same period, the prevalence rates in the community (for adults and children analyzed together) ranged from 19% to 29% for psychotropics, 18% to 23% for anticonvulsants, and 35% to 45% for psychotropic and/or anticonvulsant drugs. An analysis of the patterns of medication use showed that patient demographic, physical, social, behavioral, and psychiatric variables, as well as a number of staff variables, were correlated with use of pharmacotherapy in the entire population of individuals with mental retardation. A substantial number of individuals with mental retardation appeared to be prescribed psychotropic medications that may have been inappropriate for their diagnosis.

Objectives: The aim of this study was to better understand suicides in children and adolescents using records from the Office of the Medical Examiner of Virginia from 1987 to 2003. Main findings, key data, and statistics: Suicide accounted for 16.8% of unnatural deaths. Suicide rates were highest for Caucasians. Guns were the most common method of death for suicides, followed by hanging and poisoning. Poisoning other than carbon monoxide accounted for 7.8% of suicides, with tricyclic antidepressants (TCAs) the most identifiable poison. Female youths were 10 times more likely to die from TCAs than male youths, after adjusting for race and age. Conclusions: Guns and hanging were the principal methods of suicide. Among the antidepressants, TCAs have been the most common poisons used in suicide. Increasing age was a powerful determinant of suicide. Some patients may have stockpiled their TCAs for a while before their TCA overdose. Other suicide victims may have used TCA supplies from family members. Hence, some of the suicide victims may not have taken TCAs on a regular basis before committing suicide. Further exploration of TCA-induced suicidal thoughts is needed. Conclusions cannot be made at the time about the precise role that TCAs played in TCA-induced suicide reported in our study.

There are two divergent viewpoints on the phenomenology and outcome of bipolar I (BP I) disorder in youth. Disparities evolved as unintended consequences from investigators' inconsistencies both in translating the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, DSM-III-R, and DSM-IV criteria and in operationalizing them differently in their standardized assessments. Rates of conservatively diagnosed BP I are lower both in community studies of youths than in adults and from liberally defined BP I in youths. Rates of co-occurring attention-deficit hyperactivity disorder (ADHD) are lower in conservatively than liberally defined children and adolescents with BP I. Rates of both BP I and of ADHD are lower in offspring of BP I probands, and outcome more closely approximates that of adults with BP I in conservatively versus liberally defined children and teens with BP I. Both perspectives can claim evidence for reliability and validity that support their positions. However, the samples are so different that it is difficult to compare studies conducted from these different perspectives.

The active (1994) and closed (1988 to 1992) outpatient records of youths seen in four separate community mental health centers (CMHC) in Baltimore County, Maryland were reviewed in mid-1994 to document recent changes in the medication-prescribing practices of local child psychiatrists. Inpatient summaries of previously hospitalized CMHC youths were also reviewed to supplement the outpatient medication assessment with hospital data. This regional survey of medication treatments in child psychiatry revealed that, during the half decade before 1994, there was an increase in overall psychotropic medication treatment, multiple concurrent medication treatments (polypharmacy), and antidepressant treatment with serotonin reuptake inhibitors (SRIs). Inpatient youths were consistently prescribed more psychotropic medications and diagnosed more frequently with major depressive disorder than outpatients. Medications typically used to first treat mood disorders became the predominant medication prescribed for both outpatients and inpatients by child psychiatrists in 1994, leading to a proportional decline in prescribed stimulant treatment. The shift from tricyclic antidepressants to SRI antidepressants in the 1990s by child psychiatrists matches the same recent practice shift by adult psychiatrists. Likewise, the increased prescription of drugs to treat mood disorders and the increased rate of polypharmacy notable of late among child psychiatrists now also mirrors adult psychiatry practice. Wide geographic variations in neuroleptic and antidepressant medication patterns were noted, even among facilities in the same metropolitan region. After psychiatric hospitalization, most youths who continued treatment at a CMHC outpatient clinic discontinued their inpatient medications within 3 months; the sole exception were children who had been placed on psychostimulants.

This study was undertaken to analyze inpatient prescribing patterns of psychotropic drugs in a child psychiatric hospital from 1991-1998. Hospital pharmacy dispensing data were reviewed. Total admissions, first admissions, and readmissions were identified, and medication status of all patients at admission and at discharge was ascertained. Patterns of total psychotropic drug use and proportionate use of each drug class (antidepressants, mood stabilizers, antipsychotics stimulants, and alpha-2 antagonists) were evaluated. Controlling for the 2.3-fold rise in hospital admissions, there was a 73.0% increase in the use of psychotropic drugs from 1991-1998. The greatest relative increase was in the use of alpha-2 antagonists (from 3.3% to 23.6%). Significant increases were also observed for antidepressants (from 35.6% to 77.3%), mood stabilizers (from 14.9% to 32.6%), and stimulants (from 10.5% to 20.6%). Antipsychotic use showed no net change, although use of atypical agents largely supplanted that of conventional drugs. These findings document a marked and continuing increase in psychotropic drug use in child psychiatric inpatients during the 1990s. This trend occurred against a background of increased hospital admissions and shorter lengths of stay. Most of the increased use is accounted for by newer agents, even though data supporting their efficacy and safety in this population are limited.