Rachel G. Klein

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.

Fluvoxamine for the Treatment of Anxiety Disorders in Children and Adolescents

BACKGROUND Drugs that selectively inhibit serotonin reuptake are effective treatments for adults with mood and anxiety disorders, but limited data are available on the safety and efficacy of serotonin-reuptake inhibitors in children with anxiety disorders. METHODS We studied 128 children who were 6 to 17 years of age; who met the criteria for social phobia, separation anxiety disorder, or generalized anxiety disorder; and who had received psychological treatment for three weeks without improvement. The children were randomly assigned to receive fluvoxamine (at a maximum of 300 mg per day) or placebo for eight weeks and were evaluated with rating scales designed to assess the degree of anxiety and impairment. RESULTS Children in the fluvoxamine group had a mean (+/-SD) decrease of 9.7+/-6.9 points in symptoms of anxiety on the Pediatric Anxiety Rating Scale (range of possible scores, 0 to 25, with higher scores indicating greater anxiety), as compared with a decrease of 3.1+/-4.8 points among children in the placebo group (P<0.001). On the Clinical Global Impressions-Improvement scale, 48 of 63 children in the fluvoxamine group (76 percent) responded to the treatment, as indicated by a score of less than 4, as compared with 19 of 65 children in the placebo group (29 percent, P<0.001). Five children in the fluvoxamine group (8 percent) discontinued treatment because of adverse events, as compared with one child in the placebo group (2 percent). CONCLUSIONS Fluvoxamine is an effective treatment for children and adolescents with social phobia, separation anxiety disorder, or generalized anxiety disorder.

Long-Term Outcome of Hyperactive Children: A Review

Reports of adolescent outcome in attention deficit hyperactivity disorder have uniformly indicated high rates of behavioral problems including cognitive impairment. Dysfunction is markedly reduced in adulthood, but the pattern of outcome remains unchanged except for failure to document cognitive deficits. In adulthood, dysfunction is characterized by antisocial personality and substance (nonalcohol) use disorders. These are in turn associated with criminality. The little existing information on girls with attention deficit hyperactivity disorder does not suggest a worse outcome than for boys. Attempts to identify the children most likely to have a poor outcome have been largely unsuccessful.

Long-term Prognosis in Attention-Deficit/Hyperactivity Disorder

The authors have traced the developmental course of ADHD from childhood to adulthood, showing that it is a bumpy road for many. In early and middle adolescence, relative deficits are seen in academic and social functioning, ADHD symptoms remain problematic in two thirds to three quarters of these children, and antisocial behaviors, in some cases amounting to CD, are common. Many of these same difficulties persist into the late teenage years. Deficits continue to be observed in academic and social domains (compared with controls, probands exhibit lower grades, more courses failed, worse performance on standardized tests, have fewer friends, and are rated less adequate in psychosocial adjustment). About two fifths continue to experience ADHD symptoms to a clinically significant degree. One quarter to one third have a diagnosed antisocial disorder, and two thirds of these individuals are arrested. Also, drug abuse is observed in a significant minority of these youths. Importantly, the greatest risk factor for the development of antisocial behavior and substance abuse by the late teenage years is the maintenance of ADD symptoms. When evaluated in their mid-twenties, dysfunctions are apparent in these same areas. Compared with controls, probands complete less schooling, hold lower-ranking occupations, and continue to suffer from poor self-esteem and social skills deficits. In addition, significantly more probands than controls exhibit an antisocial personality and, perhaps, a substance use disorder in adulthood. Furthermore, many do not outgrow all facets of their childhood syndrome. These relative deficits, however, do not tell the whole story of the ADHD childs adult fate. Indeed, nearly all probands were gainfully employed. Furthermore, some had achieved a higher-level education (e.g., completed Masters degree, enrolled in medical school) and occupation (e.g., accountant, stock broker). In addition, a full two thirds of these children showed no evidence of any mental disorder in adulthood. In conclusion, although ADHD children, as a group, fare poorly compared with their non-ADHD counterparts, the childhood syndrome does not preclude attaining high educational and vocational goals, and most children no longer exhibit clinically significant emotional or behavioral problems once they reach their mid-twenties.

Educational and Occupational Outcome of Hyperactive Boys Grown Up

OBJECTIVE Little is known about the adult outcome of attention-deficit hyperactivity disorder (ADHD), a very prevalent childhood disorder that is known to affect deleteriously academic performance and other areas of child functioning. This study represents a third wave of evaluations that examine the long-term educational achievement and occupational rank of children with ADHD. METHOD This is a prospective follow-up of white boys of average intelligence whose ADHD was clinically diagnosed according to systematic criteria at an average age of 7 years. Follow-up intervals range from 15 to 21 years (mean, 17 years). At average age 24 years, 85 probands (representing 82% of the childhood cohort) and 73 controls (84%) were directly interviewed by trained clinicians who were blind to group membership. RESULTS First, probands completed significantly less formal schooling than controls (about 2 years less, on average). Second, probands had lower-ranking occupational positions than controls. Finally, these disadvantages were not accounted for by adult mental status. CONCLUSIONS The present study suggests that childhood ADHD predisposes to specific disadvantages and continues to affect important functional domains unrelated to current psychiatric diagnosis.

The Pediatric Anxiety Rating Scale (PARS): Development and psychometric properties

OBJECTIVE To describe the development and psychometric properties of the Pediatric Anxiety Rating Scale (PARS), a clinician-rated instrument for assessing the severity of anxiety symptoms associated with common DSM-IV anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) in children. METHOD As part of a multisite study of the efficacy of fluvoxamine, 128 children (aged 6-17) and their parents were interviewed weekly with the PARS. Data from multiple raters on a subsample of children (using live and videotaped interviews) were used to evaluate interrater reliability. Internal consistency, test-retest reliability, and validity (convergent, divergent) also were evaluated. RESULTS The PARS showed high interrater reliability, adequate test-retest reliability, and fair internal consistency. Convergent and divergent validity were satisfactory. PARS scores were sensitive to treatment and paralleled change in other measures of anxiety symptoms and global improvement. CONCLUSIONS The PARS is a useful clinician-rated instrument for assessing pediatric anxiety symptoms, severity, and impairment, particularly in treatment studies. Further study of the psychometric properties is warranted.

Attention-deficit hyperactivity and conduct disorder : comorbidity and implications for treatment

The distinguishing and overlapping features of attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD) are discussed. Conclusions regarding comorbidity, treatment efficacy, and long-term outcome can be influenced by several factors, including diagnostic procedures and sample characteristics. The need to distinguish between referred and non-referred samples is particularly crucial when considering treatment and comorbidity issues. The efficacy of psychosocial and pharmacological treatments in ADHD and CD children is reviewed as are the few studies of psychostimulant medication in co-morbid youngsters. Suggestions regarding treatment planning and recommendations for treatment and research are described.

Age of Methylphenidate Treatment Initiation in Children with ADHD and Later Substance Abuse: Prospective Follow-Up into Adulthood

OBJECTIVE Animal studies have shown that age at stimulant exposure is positively related to later drug sensitivity. The purpose of this study was to examine whether age at initiation of stimulant treatment in children with attention deficit hyperactivity disorder (ADHD) is related to the subsequent development of substance use disorders. METHOD The authors conducted a prospective longitudinal study of 176 methylphenidate-treated Caucasian male children (ages 6 to 12) with ADHD but without conduct disorder. The participants were followed up at late adolescence (mean age=18.4 years; retention rate=94%) and adulthood (mean age=25.3; retention rate=85%). One hundred seventy-eight comparison subjects also were included. All subjects were diagnosed by blinded clinicians. The Cox proportional hazards model included the following childhood predictor variables: age at initiation of methylphenidate treatment, total cumulative dose of methylphenidate, treatment duration, IQ, severity of hyperactivity, socioeconomic status, and lifetime parental psychopathology. Separate models tested for the following four lifetime outcomes: any substance use disorder, alcohol use disorder, non-alcohol substance use disorder, and stimulant use disorder. Other outcomes included antisocial personality, mood, and anxiety disorders. RESULTS There was a significant positive relationship between age at treatment initiation and non-alcohol substance use disorder. None of the predictor variables accounted for this association. Post hoc analyses showed that the development of antisocial personality disorder explained the relationship between age at first methylphenidate treatment and later substance use disorder. Even when controlling for substance use disorder, age at stimulant treatment initiation was significantly and positively related to the later development of antisocial personality disorder. Age at first methylphenidate treatment was unrelated to mood and anxiety disorders. CONCLUSIONS Early age at initiation of methylphenidate treatment in children with ADHD does not increase the risk for negative outcomes and may have beneficial long-term effects.

Lifetime criminality among boys with attention deficit hyperactivity disorder: a prospective follow-up study into adulthood using official arrest records.

This study investigates the relationship between childhood attention deficit hyperactivity disorder (ADHD) and later criminality. White boys (n=207, ages 6-12) with ADHD, free of conduct disorder, were assessed at ages 18 and 25 by clinicians who were blind to childhood status. A non-ADHD group served as comparisons. Lifetime arrest records were obtained when subjects were 38 years old for subjects who resided in New York State throughout the follow-up interval (93 probands, 93 comparisons). Significantly more ADHD probands than comparisons had been arrested (47% vs. 24%), convicted (42% vs. 14%), and incarcerated (15% vs. 1%). Rates of felonies and aggressive offenses also were significantly higher among probands. Importantly, the development of an antisocial or substance use disorder in adolescence completely explained the increased risk for subsequent criminality. Results suggest that even in the absence of comorbid conduct disorder in childhood, ADHD increases the risk for developing antisocial and substance use disorders in adolescence, which, in turn, increases the risk for criminal behavior in adolescence and adulthood.

Parent-child agreement in clinical assessment of anxiety and other psychopathology: A review

Abstract It is standard clinical practice to interview both parent and child to formulate childrens psychiatric diagnoses. This paper reviews the literature on parent-child agreement. Although many studies have appeared, only a few report on anxiety disorders. On the whole, there is poor agreement between children and parents. This finding raises the question as to which is more valid. To date, no investigation has addressed the issue of relative validity. Given the discrepancy between informants, and the lack of knowledge concerning which is the more accurate source, it seems desirable to obtain diagnostic information from both children and parents to assess childrens anxiety symptoms.