Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial.

OBJECTIVE: To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study. METHOD: Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks. Subjects who had not responded after 6 weeks could discontinue the double-blind phase of the study and enter a long-term, open-label trial of fluvoxamine. Analyses used an intent-to-treat sample with a last-observation-carried-forward method. RESULTS: Mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores with fluvoxamine were significantly (p < .05) different from those with placebo at weeks 1, 2, 3, 4, 6, and 10. Significant (p < .05) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits. Based on a 25% reduction of CY-BOCS scores, 42% of subjects taking fluvoxamine were responders compared with 26% taking placebo. Forty-six (19 fluvoxamine, 27 placebo) of 120 randomized subjects discontinued early. Adverse events with a placebo-adjusted rate greater than 10% were insomnia and asthenia. CONCLUSIONS: Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD.

Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders.

BACKGROUND: This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders. METHOD: Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations. RESULTS: No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score. CONCLUSION: Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.

Twelve-month outcome in bipolar patients with and without personality disorders.

BACKGROUND: We studied the 12-month course of illness after hospitalization for patients with a DSM-III-R diagnosis of bipolar disorder, manic or mixed episode, to identify the impact of a co-occurring personality disorder on measures of outcome. METHOD: Fifty-nine patients with bipolar disorder hospitalized for the treatment of a manic or mixed episode were recruited. Diagnostic, symptomatic, and functional evaluations were obtained at the index hospitalization. Personality disorders were assessed using the Structured Clinical Interview for DSM-III-R, personality disorders version (SCID-II). Patients were then reevaluated at 2, 6, and 12 months after discharge to assess syndromic, symptomatic, and functional recovery. Factors associated with outcome were identified using multivariate analyses. RESULTS: Survival analyses showed that in the 12-month follow-up period, subjects with bipolar disorder and co-occurring personality disorder were significantly less likely to achieve recovery. Logistic regression analyses indicated that both a diagnosis of personality disorder and noncompliance with treatment were significantly associated with lack of syndromic recovery. CONCLUSION: Co-occurring personality disorders in patients with bipolar disorder are associated with poor outcome after hospitalization for mania.

Lower dosages of phentermine-fenfluramine given in the afternoon: five cases with significant weight loss.

Phentermine and fenfluramine are widely used in the treatment of obesity. Despite the fact that primary pulmonary hypertension and mitral valve insufficiency have been associated with fenfluramine use, many of these patients need medication to achieve weight loss. Small degrees of weight loss have been shown to significantly improve obesity-related medical conditions such as hypertension, hypercholesterolemia, and noninsulin-dependent diabetes mellitus. Current practice is to give phentermine and fenfluramine in the morning and afternoon. Doses for phentermine have ranged from 15 to 37.5 mg and for fenfluramine from 20 to 120 mg per day. We report five cases of severely obese women with medical complications who were treated with phentermine 8 mg twice per day (at 1:00 p.m. and 4:00 p.m.) and fenfluramine 20 mg per day (at 4:00 p.m.). Because many obese patients skip breakfast and eat more in the afternoon and evening, medication was dosed in order to cover these high-risk eating periods. Overall, these patients lost a mean of 22.4% of their initial weight (range 18.6% to 32.8%) over an average of 8.4 months (range 3.5 to 16 months). These cases suggest that short-term weight loss can be achieved with a low dose of fenfluramine when both medications are given in the afternoon to better target the eating patterns of obese subjects.

The psychiatric diagnoses of twenty-two adolescents who have sexually molested other children.

The purpose of this study was to assess the prevalence of specific psychiatric disorders in adolescents who have sexually molested other children. Twenty-two adolescent males (aged 13 to 17 years) who sexually molested a child at least once were evaluated with structured clinical interviews for DSM-III-R axis I disorders. All subjects met lifetime DSM-III-R criteria for pedophilia (with the exception of the age requirement), 21 (95%) for two or more paraphilias, 18 (82%) for a mood disorder (12 [55%] for a bipolar disorder), 12 (55%) for an anxiety disorder, 11 (50%) for a substance use disorder, and 12 (55%) for an impulse-control disorder. Also, 12 (71%) of 17 subjects were diagnosed with attention-deficit/hyperactivity disorder, and 16 (94%) with conduct disorder. We conclude that some adolescent child molesters may have pedophilia or other paraphilias. Other axis I disorders with impulsive features, especially conduct, attention-deficit/hyperactivity, bipolar, and substance use disorders, may also be found in these adolescents.

An adolescent male with multiple paraphilias successfully treated with fluoxetine.

Little is known about the psychiatric diagnosis and treatment of adolescents who sexually offend. We therefore describe an adolescent sex offender who met DSM-IV criteria for multiple paraphilias (except for the age criterion), bipolar type II disorder, and OCD, whose paraphilic urges and behaviors, depression, and violent obsessions responded to open label fluoxetine after failing to respond to long-term residential treatment. Although only a single and uncontrolled observation, this case suggests that some adolescent sex offenders may in fact have paraphilias, and that paraphilias in adolescents, like those in adults, may respond to serotonin reuptake inhibitors.

Newer antidepressants. Beyond selective serotonin reuptake inhibitor antidepressants.

This article outlines the use of alternative agents to TCAs and SSRIs. Features of the more commonly used alternative antidepressant agents are outlined. In addition, antidepressant agents that are currently either under development or used in other countries are indicated for completeness because it seems likely that many of these will be introduced in the United States within the next few years. Many of these agents will be used by pediatricians and child psychiatrists for treatment of depression in children, and although much further research is needed, the future for alternative antidepressants and augmenting strategies is extremely promising.

Phenomenology of adolescent and adult mania in hospitalized patients with bipolar disorder.

OBJECTIVE: Although available data suggest that bipolar disorder most commonly begins in adolescence, it has often been underrecognized and misdiagnosed in this age group. The authors hypothesized that this might in part be because adolescent mania is phenomenologically different from adult mania. To test this hypothesis, they compared a cohort of adolescents hospitalized for acute mania with a group of hospitalized acutely manic adults. METHOD: The authors compared symptomatic differences between 40 adolescent (ages 12-18 years) and 88 adult (ages 19-45 years) bipolar patients hospitalized for acute mania. They also compared the two groups with respect to demographic characteristics, psychiatric comorbidity, family history, and short-term outcome. RESULTS: Compared with adults, adolescent patients displayed a significantly higher rate of mixed bipolar disorder and a significantly lower rate of psychotic features (by DSM-III-R criteria), as well as higher ratings for many depressive symptoms (including suicidality and depressed mood) and lower ratings for thought disorder and delusions. Adolescents also displayed a significantly lower rate of substance abuse and significantly higher rates of familial mood disorder and drug abuse or dependence. CONCLUSIONS: Significant differences were found in the phenomenology of adolescent and adult mania in this study. The reasons for these differences are not known. Possible explanations include artifact due to methodological limitations and differences between adolescents and adults in familial loading for mood or substance use disorders or in developmental or maturational stage.

Nicotine for the treatment of Tourette's syndrome.

Recent evidence has demonstrated that nicotine may obtund the symptoms of Tourette's syndrome (TS). TS is a neuropsychiatric disorder characterized by motor and vocal tics, obsessions and compulsions, and frequently with impulsivity, distractibility, and visual-motor deficits. While neuroleptics, such as haloperidol, are most effective for treatment of the motor and vocal tics of TS, these medications have many side effects. In this article, we review the evidence, consistent with findings in animals, that administration of nicotine (either 2 mg nicotine gum or 7 mg transdermal nicotine patch) potentiates the therapeutic properties of neuroleptics in treating TS patients and that a single patch may be effective for a variable number of days. These findings suggest that transdermal nicotine could serve as an effective adjunct to neuroleptic therapy for TS.

Personality disorders in first- and multiple-episode mania.

We compared rates of DSM-III-R personality disorders in 33 first-episode and 26 multiple-episode bipolar patients. Patients were evaluated with the patient and personality disorders versions of the Structured Clinical Interview for DSM-III-R. Significantly more multiple-episode patients (65%) met DSM-III-R criteria for a personality disorder than did first-episode patients (33%). Race was also associated with a diagnosis of a personality disorder. Personality disorders may be associated with multiple affective episodes in bipolar patients.

An open study of the effects of sertraline on adolescent major depression.

This open study investigated the effects of sertraline in treating 13 adolescents, ages 12 to 18, who were hospitalized for treatment of a major depressive episode. The sample included 7 adolescents with nonendogenous depression and 6 with endogenous depression, as diagnosed by both Research Diagnostic Criteria (RDC) and Kiddie-SADS-P DSM-III-R endogenous subtype criteria. These patients were followed for an inpatient length of stay ranging from 9 to 38 days (mean 19 days), with later outpatient follow-up for a total of 12 weeks. Measures of depression were found to improve significantly, including suicidal ideation and most of the DSM-III-R symptoms of major depression. Sertraline (mean 110 mg or 1.96 mg/kg daily) significantly decreased scores on the 24-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale from premedication baseline to treatment week 12, and also between weeks 1 (after a large week 1 improvement, presumably due to nondrug effects) and 12. There was a small but significant improvement on the Children's Global Assessment Scale between baseline and week 12, but the Family Global Assessment Scale showed no significant change; neither global assessment scale showed significant effects between weeks 1 and 12. Sleep disturbance was common (69%) after 12 weeks of treatment, but clinically significant improvements in sleep patterns were also observed. This open-label prospective study suggests that sertraline might be useful in treating adolescents with major depression. Adverse effects, mainly insomnia and drowsiness, were relatively common but usually manageable. One patient developed mania after 8 days of sertraline treatment at a dose of 100 mg daily.

Attention deficit hyperactivity disorder in adolescent mania.

OBJECTIVE: The purpose of this study was to examine the rate of attention deficit hyperactivity disorder in adolescents with bipolar disorder and to explore the potential effects of comorbid attention deficit hyperactivity disorder on the phenomenology of adolescent bipolar disorder. METHOD: The authors assessed the rate of attention deficit hyperactivity disorder for adolescents with bipolar disorder who were hospitalized for treatment of acute mania or hypomania. RESULTS: Eight (57%) of 14 adolescent bipolar patients also met DSM-III-R criteria for attention deficit hyperactivity disorder. Patients with both disorders were more likely to be male and Caucasian and to have mixed rather than manic bipolar disorder. Patients with attention deficit hyperactivity disorder had a higher mean total score on the Young Mania Rating Scale than patients with bipolar disorder alone. CONCLUSIONS: Although preliminary, these findings may have important implications regarding the potential relationship between bipolar disorder and attention deficit hyperactivity disorder.

Behavioural problems among preschool age children in Shanghai: analysis of 3,000 cases.

This paper reports the preliminary findings of an epidemiological study of 3,000 children ages four and five in the Shanghai area. Associations were investigated between problems in the narrow band syndromes of the Achenbach Child Behavior Checklist and certain sociodemographic variables (a one-child family, other social circumstances related to the family). No strong evidence emerged of a distinct psychopathology associated with children from single-child families, although there was a significant correlation between being an only child and having social withdrawal problems. Delinquent behaviour and hyperactivity were more frequent among boys, while somatic complaints, schizoid or anxious, and depression were more frequent among girls. A four year follow-up study of 433 children from the original group who continued to have problems showed a marked increase in hyperactive syndrome problems; this suggests the existence of a clinically identifiable group of behaviourally disturbed children. Early identification allows for early treatment and comparison of the relative efficacy of early and late treatment approaches.

The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder.

We studied the effects of chewing nicotine gum on tic frequency and severity in 10 patients with Tourette's disorder (TD) on haloperidol, versus 9 untreated TD patients; placebo gum was administered to 5 of these untreated patients. Videotapes of patients during a 2-hr period of 30 min baseline, 30 min gum chewing, and two 30-min postgum-chewing periods were utilized. For those TD patients on haloperidol, significant reductions occurred in tic frequency and severity during the gum-chewing and the two postgum-chewing periods. Nicotine gum alone caused a decrease in tic frequency only during gum-chewing and one postgum-chewing period, while placebo gum showed no effect. In this study, nicotine markedly potentiated haloperidol effects in treating TD, and showed lesser effects on TD when used alone.

Nicotine potentiation of haloperidol in reducing tic frequency in Tourette's disorder.

In an open, nonblind study, 10 patients with Tourette's disorder who were being treated with haloperidol were videotaped before, while, and after chewing nicotine gum. The frequency of tics was reduced significantly during the 30-minute gum-chewing period and during the 1 hour after gum chewing. Nicotine appears to potentiate haloperidol effects in patients with Tourette's disorder.

Nicotine potentiates haloperidol-induced catalepsy and locomotor hypoactivity.

Nicotine was found to potentiate the catalepsy and reduced locomotion following the administration of haloperidol. The ability of various doses of nicotine (0.1, 0.2, or 0.3 mg/kg) to potentiate the catalepsy produced by haloperidol (0.1, 0.2 or 0.4 mg/kg) was investigated. Nicotine potentiated the cataleptic effects of both the 0.2 and 0.4 mg/kg doses of haloperidol, but had no effect following the lowest (0.1 mg/kg) dose of haloperidol. The nicotine potentiation of catalepsy produced by the highest dose of haloperidol was independent of the dose of nicotine used. Nicotine alone did not produce catalepsy. A second experiment evaluated the ability of nicotine to potentiate the decreases in spontaneous locomotor activity produced by haloperidol. Animals received nicotine (0.1 mg/kg) alone or in conjunction with haloperidol (0.1 or 0.4 mg/kg) and were tested in Digiscan Animal Monitors. Haloperidol produced a dose-related decrease in locomotion. Nicotine significantly potentiated the hypoactivity produced by both doses of haloperidol. These results indicated that: 1) nicotine produces a significant potentiation of both the catalepsy and locomotor decreases following haloperidol and 2) the Digiscam Animal Activity Monitors may provide a more sensitive assessment of the interaction between nicotine and haloperidol than the catalepsy bat test. These data suggest that adjunct treatment with nicotine may prove useful for treating neuroleptic responsive disorders such as Tourette Syndrome, schizophrenia and Huntington's disease.