A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder.

Twenty-six children and adolescents with severe primary obsessive-compulsive disorder receiving long-term clomipramine hydrochloride maintenance treatment (mean +/- SD, 17.1 +/- 8.3 months; range, 4 to 32 months) entered an 8-month double-blind desipramine hydrochloride substitution study to assess the necessity of continued drug treatment. All patients received clomipramine for the first 3 months, then half continued with clomipramine therapy (nonsubstituted group) and half had desipramine blindly substituted for the next 2 months; all subjects again received clomipramine for the last 3 study months. Eight (89%) of nine of the substituted and only two (18%) of 11 of the nonsubstituted group subjects relapsed during the 2-month comparison period. Long-term clomipramine treatment seems necessary for this population of children and adolescents with obsessive-compulsive disorder. However, even patients receiving maintenance clomipramine treatment throughout the entire study had continued obsessive-compulsive symptoms, which varied in severity over time.

Treatment of obsessive-compulsive disorder with clomipramine and desipramine in children and adolescents. A double-blind crossover comparison.

Forty-eight children and adolescents with severe primary obsessive-compulsive disorder completed a 10-week double-blind crossover trial of clomipramine hydrochloride (mean dose [+/- SD], 150 +/- 53 mg/d) and desipramine hydrochloride (mean dose [+/- SD], 153 +/- 55 mg/d). Clomipramine was clearly superior to desipramine in significantly reducing obsessive-compulsive symptoms. Age at onset, duration and severity of illness, type of symptom, and plasma drug concentrations did not predict clinical response to clomipramine. Sixty-four percent of patients who received clomipramine as their first active treatment showed at least some sign of relapse during desipramine treatment. We further document the specificity of the antiobsessional effect of clomipramine and the need for maintenance treatment.

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder.

The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.

High prevalence of obsessive-compulsive symptoms in patients with Sydenham's chorea.

The 20-item Leyton Obsessional Inventory--Child Version was completed by children and adolescents who had had Sydenham's chorea (N = 23) or rheumatic fever without chorea (N = 14). The Sydenham's chorea subjects had significantly more obsessive thoughts and compulsive behaviors and significantly greater interference from these behaviors. Three Sydenham's chorea patients but no rheumatic fever patients had substantial obsessional interference and met criteria for obsessive-compulsive disorder when interviewed by telephone. This suggests that obsessive-compulsive disorder, at least in some patients, may be due to basal ganglia dysfunction.

Childhood rituals: normal development or obsessive-compulsive symptoms?

The symptoms of obsessive compulsive disorder (OCD) have been viewed as extreme variants of normal developmental rituals and superstitiousness; however, difference in timing, content, and severity argue against this continuum. In a systematic comparison of 38 children with severe primary OCD and 22 matched normal controls, parents were interviewed about their child's early developmental rituals and current superstitions. Children were asked about superstitious beliefs. Children with OCD did not differ significantly from controls in number or type of superstitions. However, parents of the OCD children reported significantly more "marked" patterns of early ritualistic behavior than did parents of normal controls. When behaviors resembling primary OCD symptoms were excluded, other rituals did not differ leaving open the possibility that such behaviors were early manifestations of the disorder. Only a prospective study can determine whether these results reflect preclinical OCD or are an artifact of biased recall.

A double-blind comparison of clomipramine and desipramine in the treatment of trichotillomania (hair pulling)

Trichotillomania, an irresistible impulse to pull out one's own hair, is a chronic psychiatric illness that causes severe discomfort, interferes with daily activities, and leads to social isolation. Treatment is usually unsatisfactory. Thirteen women with severe trichotillomania completed a 10-week double-blind, crossover trial of clomipramine, a new tricyclic antidepressant agent with selective antiobsessional effects, and desipramine, a standard tricyclic antidepressant. Treatment with clomipramine resulted in significantly greater improvement in symptoms than desipramine, as indicated by physicians' ratings of the women's clinical progress on a scale in which lower scores indicate improvement (mean [+/- SD] scores: at base line, 10.0; after desipramine treatment, 8.7 +/- 2.4; after clomipramine treatment, 4.7 +/- 3.1; P = 0.006) and by scores on a trichotillomania-impairment scale, in which higher scores indicate greater impairment (at base line, 6.8 +/- 1.7; after desipramine treatment, 6.2 +/- 1.7; after clomipramine treatment, 4.2 +/- 2.7; P = 0.03). The severity of symptoms (mean base-line score, 15.9 +/- 3.8) was reduced more by clomipramine (10.6 +/- 6.4) than by desipramine (14.4 +/- 3.9). The patients reported that the compulsion decreased in intensity and that they were more able to resist the urge to pull out their hair during treatment with clomipramine. We conclude that clomipramine appears to be effective in the short-term treatment of trichotillomania.

Lack of seasonal variation in pediatric lumbar cerebrospinal fluid neurotransmitter metabolite concentrations.

Seasonal variation of cerebrospinal fluid (CSF) monoamines, particularly 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) has been reported for psychiatrically ill and normal adults. Circannual variability was examined for a group of 72 children (mean age = 159.4 +/- 40.3 (SD), range 77-238 months), with a primary diagnosis of obsessive-compulsive disorder (OCD) or disruptive behavior disorder (DBD) (attention deficit disorder, oppositional disorder and/or conduct disorder), from whom CSF had been obtained systematically. There were no seasonal differences in mean concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), HVA, or 5-HIAA, either for the group as a whole, for the separate diagnostic (OCD vs DBD) categories or for the pre-pubertal subgroup. Log-corrected HVA concentrations for the Tanner IV and V subgroup differed by season with summer concentrations less than those of fall (P = 0.06) and winter (P = 0.005). The results suggest that pubertal changes may play a role in any expression of circannual variability.