Vivek Kusumakar

Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial

OBJECTIVE To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS Paroxetine is generally well tolerated and effective for major depression in adolescents.

Measuring Peer Pressure, Popularity, and Conformity in Adolescent Boys and Girls: Predicting School Performance, Sexual Attitudes, and Substance Abuse

Existing measures of peer pressure and conformity may not be suitable for screening large numbers of adolescents efficiently, and few studies have differentiated peer pressure from theoretically related constructs, such as conformity or wanting to be popular. We developed and validated short measures of peer pressure, peer conformity, and popularity in a sample (n = 148) of adolescent boys and girls in grades 11 to 13. Results showed that all measures constructed for the study were internally consistent. Although all measures of peer pressure, conformity, and popularity were intercorrelated, peer pressure and peer conformity were stronger predictors of risk behaviors than measures assessing popularity, general conformity, or dysphoria. Despite a simplified scoring format, peer conformity vignettes were equal to if not better than the peer pressure measures in predicting risk behavior. Findings suggest that peer pressure and peer conformity are potentially greater risk factors than a need to be popular, and that both peer pressure and peer conformity can be measured with short scales suitable for large-scale testing.

Hippocampal volume in early onset depression.

BackgroundAbnormalities in limbic structures have been implicated in major depressive disorder (MDD). Although MDD is as common in adolescence as in adulthood, few studies have examined youth near illness onset in order to determine the possible influence of atypical development on the pathophysiology of this disorder.MethodsHippocampal volumes were measured in 17 MDD subjects (age = 16.67 ± 1.83 years [mean ± SD]; range = 13 – 18 years) and 17 age- and sex-matched healthy controls (16.23 ± 1.61 years [mean ± SD]; 13 – 18 years) using magnetic resonance imaging (MRI).ResultsAn analysis of covariance revealed a significant difference between MDD and control subjects (F = 8.66, df = 1, 29, P = 0.006). This was more strongly localized to the left hippocampus (P = 0.001) than the right hippocampus (P = 0.047).ConclusionsOur findings provide new evidence of abnormalities in the hippocampus in early onset depression. However, our results should be considered preliminary given the small sample size studied.

A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia.

This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate (approved in the USA, August 2009) for adult patients with acutely exacerbated schizophrenia. The patients (N = 652) were randomly assigned (1:1:1:1) to paliperidone palmitate at 25, 100, or 150 mg eq. or placebo in this 13-week double-blind study. The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or muscle on day 8 and then once monthly (days 36 and 64). No oral supplementation was used. Target plasma levels were achieved by day 8 in all paliperidone palmitate groups. The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly (P ≤ 0.034) in all the paliperidone palmitate dose-groups versus placebo. Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle. Common treatment-emergent adverse events (≥2% of patients in any of the treatment groups) that occurred more frequently in the total paliperidone palmitate group versus the placebo group (with ≥1% difference) were injection-site pain (7.6% vs 3.7%), dizziness (2.5% vs 1.2%), sedation (2.3% vs 0.6%), pain in the extremity (1.6% vs 0.0%), and myalgia (1.0% vs 0.0%). The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range (25, 100, or 150 mg eq.) in adult patients with acutely exacerbated schizophrenia.Abbreviations: BMI - body mass index, CGI-S - Clinical Global Impression-Severity, EPS - extrapyramidal symptoms, ER - extended release, ITT - intent-to-treat, LAI - long-acting injectable, PANSS - Positive and Negative Syndrome Scale, PK - pharmacokinetic, PSP - Personal and Social Performance Scale, TEAE - treatment-emergent adverse events, VAS - Visual Analogue Scale

Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: a randomized, double-blind, placebo-controlled study

OBJECTIVES To evaluate the efficacy, safety, and tolerability of risperidone monotherapy for the treatment of an acute mixed or manic episode in children and adolescents with bipolar I disorder. METHODS This randomized, placebo-controlled, double-blind, 3-arm study (N = 169) included children and adolescents (ages 10-17 years) with a DSM-IV diagnosis of bipolar I disorder, experiencing a manic or mixed episode. Study participants were randomized to placebo (n = 58), risperidone 0.5-2.5 mg/day (n = 50), or risperidone 3-6 mg/day (n = 61) for 3 weeks. The primary efficacy measure was change in Young Mania Rating Scale (YMRS) total score from baseline to end point. Safety assessments included adverse event (AE) monitoring and scores on extrapyramidal symptom rating scales. RESULTS Improvement in mean YMRS total score was significantly greater in risperidone-treated subjects than in placebo-treated subjects [mean change (SD) -9.1 (11.0) for placebo; -18.5 (9.7) for risperidone 0.5-2.5 mg (p < 0.001); -16.5 (10.3) for risperidone 3-6 mg (p < 0.001)]. The most common risperidone-associated AEs were somnolence, headache, and fatigue. Mean (SD) weight gain was 0.7 (1.9) kg, 1.9 (1.7) kg, and 1.4 (2.4) kg in the placebo, risperidone 0.5-2.5 mg, and risperidone 3-6 mg groups, respectively, during this 3-week study. CONCLUSIONS At daily doses of 0.5-2.5 mg and 3-6 mg, risperidone was effective and well tolerated in children and adolescents experiencing acute manic or mixed episodes of bipolar I disorder. Results indicate that risperidone 0.5-2.5 mg has a better benefit-risk profile than risperidone 3-6 mg.

An open study of lamotrigine in refractory bipolar depression

Bipolar depressed patients (n = 22) who were refractory to treatment with a combination of divalproex sodium (DVP) and another mood stabilizer or DVP and an antidepressant for 6 weeks were treated in an open naturalistic study with an addition of lamotrigine to DVP. Sixteen out of 22 (72%) responded by the end of week 4 and none developed rash or switched to mania. The results of this preliminary study suggest that lamotrigine may be useful in bipolar depression.

Risperidone Long-Acting Injectable Monotherapy in the Maintenance Treatment of Bipolar I Disorder

BACKGROUND Treatment adherence is a significant problem in patients with bipolar disorder. This study was designed to determine the efficacy of risperidone long-acting injectable (LAI) in the maintenance treatment of bipolar I disorder. METHODS Eligible patients with current or recent manic or mixed episodes (n = 559, aged 18-65 years) were treated with open-label oral risperidone for 3 weeks (period II) and open-label risperidone LAI for 26 weeks (n = 501; period III). Patients who maintained response (n = 303) were randomly allocated 1:1 to placebo injections (n = 149) or to continue risperidone LAI (n = 154) for up to 24 months (period IV). RESULTS Most (77%) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV. Time to recurrence for any mood episode (primary outcome variable) was significantly longer in the risperidone LAI group versus placebo (p < .001); the difference was significant for time to recurrence of elevated-mood episode (p < .001) but not time to recurrence of depressive episode (p = .805). Weight gains > or = 7% (compared with the periods baseline) occurred in 15% of patients in period III; in 12% of patients on risperidone LAI and 3% of patients on placebo in period IV. CONCLUSIONS Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes, versus placebo, in this controlled, randomized study in patients with bipolar I disorder. Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI.

Proton spectroscopy in medication-free pediatric attention-deficit/hyperactivity disorder

BACKGROUND The frontal-striatal pathway has been previously implicated in the neuropathology of attention-deficit/hyperactivity disorder (ADHD). Hence, we used proton magnetic resonance spectroscopy (1H-MRS) to examine metabolite levels in the prefrontal cortex of children with ADHD. METHODS Nine age- and gender-matched case-control pairs were examined, ages 7 to 16 years. A long-echo 1H-MRS scan was acquired from the right prefrontal cortex and left striatum in all subjects. Compounds that can be visualized with 1H-MRS include N-acetyl-aspartate (NAA), glutamate/glutamine/gamma-aminobutyric acid (Glx), creatine/phosphocreatine (Cr), and choline compounds (Cho). RESULTS Frontal-striatal glutamatergic resonances were elevated in the children with ADHD as compared to healthy control subjects. No differences were noted in NAA, Cho, or Cr metabolite ratios. CONCLUSIONS These findings suggest that frontal-striatal Glx resonances may be increased in children with ADHD in comparison with healthy control subjects.

Efficacy, safety and tolerability of two risperidone dosing regimens in adolescent schizophrenia: double-blind study

BACKGROUND Effective treatments for adolescent schizophrenia are needed. AIMS To compare efficacy and safety of two dosing regimens of risperidone. METHOD Double-blind, 8-week study. Patients, 13-17 years, with an acute episode of schizophrenia, randomised 1:1 to risperidone 1.5-6.0 mg/day (regimen A; n=125) or 0.15-0.6 mg/day (regimen B; n=132). TRIAL REGISTRATION NUMBER NCT00034749. RESULTS Mean total Positive and Negative Syndrome Scale (PANSS) score improved significantly (P<0.001; effect size=0.49) from baseline to end-point for regimen A (mean=96.4 (s.d.=15.39) to mean=72.8 (s.d.=22.52)) compared with regimen B (mean=93.3 (s.d.=14.14) to mean=80.8 (s.d.=24.33)). Treatment-emergent adverse events occurred in 74% (regimen A) and 65% (regimen B) of patients; 4% of patients overall discontinued for adverse events. Mean change in body weight was 3.2 kg (s.d.=3.49) for regimen A and 1.7 kg (s.d.=3.29) for regimen B. CONCLUSIONS Adolescent patients in the regimen A group showed greater improvement in total PANSS compared with the regimen B group. Treatment was well tolerated.

Glutamatergic Changes with Treatment in Attention Deficit Hyperactivity Disorder: A Preliminary Case Series

Magnetic resonance spectroscopy, a noninvasive neuroimaging method, is a technique with the potential to measure in vivo neurochemical changes to different medication treatments. Symptoms of attention deficit hyperactivity disorder (ADHD) improved in two children treated with methylphenidate and two children treated with atomoxetine, for whom pre- and posttreatment proton magnetic resonance spectroscopy examinations were obtained to assess the relation between the neurochemical profiles in the striatum and prefrontal cortex among symptom severity and response to treatment. In the striatum, a striking decrease in the glutamate/creatine ratio (mean change 56.1%) was observed between 14 and 18 weeks of therapy in all four children with ADHD. In the prefrontal cortex, however, changes in the glutamate/creatine ratio were noted only in subjects receiving atomoxetine, not in those receiving methylphenidate. These data suggest that in vivo magnetic resonance spectroscopy measurement has the potential to assess response to psychopharmacological treatment in children with ADHD.