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The authors evaluated the neurohormonal and subjective mood response of children with anxiety disorders who were challenged with yohimbine.Seventeen children with DSM-IV diagnoses of anxiety disorders and 15 normal comparison children were given yohimbine orally (0.1 mg/kg). Neurohormonal measures and visual analog self-reports of tenseness were recorded over a 150-minute period.Yohimbine was uniformly well tolerated, and it behaviorally differentiated children with anxiety disorders from normal comparison children with higher maximum change (Deltamax) ratings of anxiety in the patients (mean=17.4 mm, SD=29.8) than in the comparison subjects (mean=0.3 mm, SD=4.4). Yohimbine-stimulated Deltamax growth hormone (GH) for children with anxiety disorders (mean=-1.5 ng/ml, SD=5.9) was significantly reduced compared to that of normal comparison children (mean=2.7 ng/ml, SD=4.5).Yohimbine selectively elevates self-rated anxiety in children with anxiety disorders and is associated with the blunting of GH in those children relative to that of comparison children. Presence of a blunted GH response to yohimbine in children with anxiety disorders is reminiscent of findings in adults with anxiety disorders, particularly panic disorder. These findings support enhanced central adrenergic sensitivity in children with anxiety disorders, as demonstrated by yohimbine-exacerbated anxiety. The findings should be reconciled with the absence of clonidine-related GH blunting in the same cohort.

Objective: The authors evaluated the relative efficacy and safety of pimozide and haloperidol in the treatment of Gilles de la Tourette’s syndrome in children and adolescents. Method: A double-blind, 24-week, placebo-controlled double crossover study of equivalent dose formulations of haloperidol and pimozide was conducted with 22 subjects, aged 7‐16 years, with Tourette’s disorder who were randomly assigned to first one active drug treatment and then the other. Biweekly assessment and flexible dose titration mimicked clinical practice. The primary outcome variable was total score on the Tourette Syndrome Global Scale. Final outcome was determined after 6 weeks of each treatment (placebo, pimozide, haloperidol), with a 2-week placebo baseline period and intervening 2-week placebo washout periods between treatments. Results: Pimozide proved significantly different from placebo in affecting the primary outcome variable, whereas haloperidol failed to have a significant effect. Haloperidol exhibited a threefold higher frequency of serious side effects and significantly greater extrapyramidal symptoms relative to pimozide. Haloperidol-associated treatment-limiting adverse events were experienced by 41% of the patients. The therapeutic doses of pimozide and haloperidol were equivalent (mean=3.4 mg/day, SD=1.6, and mean=3.5 mg/day, SD=2.2, respectively). Conclusions: At equivalent doses, pimozide is superior to haloperidol for controlling symptoms of Tourette’s disorder in children and adolescents. (Am J Psychiatry 1997; 154:1057‐1062)

Objective: Major depressive disorder in adolescents is characterized as treatment resistant, but a previous open-label trial of pulse intravenous clomipramine demonstrated rapid relief of depressive symptoms. In the present study a single intravenous dose of clomipramine (200 mg) was compared with saline placebo in a randomized controlled trial for depressed adolescents. The hypothesis was that adolescents who were treated with pulse clomipramine would exhibit lower scores on the Hamilton Depression Rating Scale at endpoint than would adolescents who received saline and that clomipramine would be superior to saline in terms of antidepressant response. Method: Sixteen nonsuicidal outpatient adolescents (mean age=16.2 years, SD=1.0) who met the DSM-III-R criteria for major depression (score on 21-item Hamilton scale, ≥18) were randomly assigned to receive either clomipramine (200 mg i.v., N=8) or saline (N=8). Assessments of depression severity were completed 36 hours and 6 days thereafter. Results: The adolescents who received pulse clomipramine treatment demonstrated significant decreases in Hamilton depression scores from baseline at 6 days but not at 36 hours. A similar decrease from baseline was found in Clinical Global Impression severity at 6 days but not 36 hours. Seven of the clomipramine-treated patients and three of the salinetreated patients had drops of 50% or more from baseline in Hamilton depression score. Conclusions: Pulse clomipramine (200 mg i.v.) is associated with dramatic reduction in depressive symptoms at day 6 after infusion, which is significantly different from the effect of placebo. (Am J Psychiatry 1997; 154:668‐673)

Objective: The authors conducted a randomized, double-blind, placebo-controlled trial of intravenous versus oral pulse loading of clomipramine in patients with obsessive-compulsive disorder to test two hypotheses: 1) intravenous pulse loading will cause greater immediate improvement than oral pulse loading and 2) patients who respond to pulse loading will continue to improve during 8 weeks of oral clomipramine treatment. Method: Fifteen patients with DSM-III-R obsessive-compulsive disorder of at least 1 year’s duration and baseline YaleBrown Obsessive Compulsive Scale scores of 17 or higher were enrolled in the study. YaleBrown scale ratings were made 4.5 days after double-blind oral or intravenous pulse loading of clomipramine, and patients were then given 150 mg/day of oral clomipramine with increases of 25 mg every 4 days to 250 mg/day as tolerated or, in two cases, other selective serotonin reuptake inhibitors (SSRIs). Results: The first hypothesis was confirmed: 4.5 days after the second pulse-loaded dose, six of seven patients given intravenous clomipramine but only one of eight given oral medication responded to the drug. After 8 weeks of oral clomipramine, the results partially supported the second hypothesis: four of six patients who had responded to intravenous clomipramine continued their improvement, but those who had responded to pulse loading did not improve statistically significantly more than those who had not. Conclusions: Intravenous pulse loading of clomipramine may be a valuable new treatment for obsessive-compulsive disorder, particularly for patients who have failed oral treatment trials. (Am J Psychiatry 1997; 154:396‐401)

Objective and Method: Although obsessive-compulsive disorder commonly occurs in many patients with Gilles de la Tourette’s syndrome, little is known about the obsessions and compulsions of Tourette’s syndrome and whether they differ from those seen in pure obsessive-compulsive disorder. The authors prospectively studied 1 0 subjects with obsessive-compulsive disorder and 15 subjects with obsessive-compulsive disorder and comorbid Tourette’s syndrome by using the Yale-Brown Obsessive Compulsive Scale, the Leyton Obsessional Inventory, and a new questionnaire designed to emphasize the differences in symptoms between these two groups. Results: Subjects with comorbid obsessive-compulsive disorder and Tourette’s syndrome had significantly more violent, sexual, and symmetrical obsessions and more touching, blinking, counting, and self-damaging compulsions. The group with obsessive-compulsive disorder alone had more obsessions concerning dirt or germs and more cleaning compulsions. The subjects who had both disorders reported that their compulsions arose spontaneously, whereas the subjects with obsessive-compulsive disorder alone reported that their compulsions were frequently preceded by cognitions. Conclusions: There are phenomenologic differences between obsessivecompulsive disorder and obsessive-compulsive disorder with comorbid Tourette’s syndrome that may reflect differential involvement of neurochemical and neuroanatomic pathways. (Am J Psychiatry 1993; 150:93-97)