Do Subtle Neurological Impairments Predict Treatment Resistance to Clomipramine in Children and Adolescents with Obsessive-Compulsive Disorder?

Abstract

A 10-week double-blind, placebo-controlled design was employed to investigate the effectiveness of clomipramine (CMI) versus placebo in 16 outpatients (ages 10-18 years) with obsessive-compulsive disorder (OCD). While a trend favoring clomipramine was observed, the difference in efficacy between clomipramine (N=8) and placebo (N=8) did not reach statistical significance, partly due to small sample size (N = 6,8). Post-hoc exclusion of two clomipramine-resistant subjects with subtle neurological impairments did, however, yield a statistically significant improvement with drug treatment. Neurological impairments are commonly seen in children with OCD, and may be a risk factor for the disorder during childhood. Speculatively, subtle neurological impairments may also predict resistance to CMI therapy in some patients, and influence the outcome of clinical and research medication trials, depending on differences in neurological inclusion and exclusion criteria.

Meta‐analysis of randomized, controlled treatment trials for pediatric obsessive‐compulsive disorder

“…All studies utilized the Children's Yale‐Brown Obsessive Compulsive Scale (CY‐BOCS; Goodman et al., 1989; Scahill et al., 1997b) as the primary OCD measure, except for Flament and colleagues (1985). A study by March and colleagues (1990) was excluded because it was part of a larger study by DeVeaugh‐Geiss and others (1992), and a study by Scahill and colleagues (1997a) was excluded because results had been published previously (Riddle et al., 1992). Two pharmacotherapy studies (Leonard et al., 1991, 1989) were excluded because the comparison group was an active comparator and not a control comparator.…”

Pediatric Psychopharmacology for Prepubertal Internalizing Disorders.

“…In 1989, clomipramine (a TCA with selectivity for serotonin reuptake blockade), became the first psychotropic medication approved by the FDA for children and adolescents with OCD. Four evidence-based published studies of clomipramine (DeVaugh-Geiss et al, 1992; Flament et al, 1985; Leonard et al, 1989; March et al, 1990) demonstrated the short-term (8 to 10 weeks) efficacy of clomipramine to placebo or desipramine. Two later studies (DeVaugh-Geiss et al, 1992; Leonard et al, 1991) demonstrated the long-term efficacy (8 to 12 months) of clomipramine.…”

Review: clomipramine is more effective than SSRIs for paediatric obsessive compulsive disorder

“…Thus, the meta-analysis reported by Geller and colleagues is remarkable in part because it illustrates the progress made in the psychopharmacology of OCD in youth. It is worth noting here that the authors included a trial (March 1990 1 ) which is a subset of a trial already included (DeVeaugh-Geiss, 1992…”