Clozapine treatment in a population of adults with mental retardation.

BACKGROUND: There is a paucity of data on the use of clozapine in patients with mental retardation and comorbid psychiatric illness. The authors describe their recent clinical experience using clozapine in treatment-refractory patients with mental retardation and severe psychiatric illness. METHOD: A retrospective review was performed on the records of all patients admitted to a university-affiliated, specialized inpatient psychiatry service who were selected for clozapine therapy from March 1994 through December 1997 (N = 33). Patients had DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder, or psychotic disorder NOS and were considered treatment resistant. All had deficits in functioning well beyond those expected for their degree of cognitive deficits and adaptive delays. RESULTS: Of 33 initial patients, 26 remained on clozapine therapy for a follow-up duration of 5 to 48 months (mean = 24.8 months). Evaluation at follow-up revealed Clinical Global Impressions-Improvement (CGI-I) scores from 1 to 4 with a mean +/- SD improvement of 2.0 +/- 0.8 (much improved). The mean +/- SD rating of the CGI-Efficacy Index was 5 +/- 2.6 (decided improvement and partial remission of symptoms with no interference from side effects). The 6 patients who were not maintained on clozapine therapy over the study period did not significantly differ from the clozapine group in gender, race, age, side effects, or diagnosis. One patient was lost to follow-up. Side effects were mild and transient with constipation being the most common (N = 10). There were no significant cardiovascular side effects and no seizures. No patients discontinued treatment due to agranulocytosis. CONCLUSION: The current investigation lends support to the conclusion that clozapine appears to be safe, efficacious, and well tolerated in individuals with mental retardation and comorbid psychiatric illness.

Auditory event-related potentials and statistical probability mapping in obsessive-compulsive disorder.

The current exploratory investigation was undertaken to replicate and extend previous findings of auditory event related potentials (ERPs) observed in obsessive-compulsive disorder (OCD). Similar to previous ERP studies, this study revealed a decreased slow wave (SW) (post P300) latency, a trend towards decreased P300 latency and a greater N200 amplitude in OCD subjects than in controls. In addition, the chronicity of OCD symptoms was correlated with the 140-170 millisecond integrated amplitude and the severity of OCD symptoms correlated with the 386-438 millisecond integrated amplitude. Current findings lend additional support to evidence suggesting OCD represents, in part, hyperarousal of the cortex.

Impaired neuropsychological functioning in Tourette's syndrome subjects with co-occurring obsessive-compulsive and attention deficit symptoms.

This study examined neuropsychological performance by 92 children with Tourette's syndrome (TS) grouped by the presence or absence of obsessive-compulsive and/or attention deficit symptoms. The identified groups did not differ with respect to age, education, age at onset of TS symptoms, or medication use. After statistical control for complex motor symptoms, impaired performance on measures of achievement and executive functioning was correlated with obsessive and obsessive/attention symptoms, but not with attention symptoms alone. The presence of both obsessive and attention symptoms identified children with impairment across several tasks. Clinical and functional implications are discussed.

Obsessive-compulsive symptom clusters and urinary amine correlates in Tourette syndrome.

This study was conducted to identify clusters of obsessive-compulsive characteristics in Tourette syndrome subjects and to explore their neurochemical correlates. Patients completed a 40-item questionnaire assessing obsessive-compulsive symptoms. Each subject had a 24-hour urine specimen collected and analyzed for a variety of biogenic amines and their metabolites. Factor analysis identified eight symptom clusters, the majority of which appeared to reflect obsessive symptoms. Consistent relationships were observed between symptom clusters and levels of catecholamine and indolamine amines and metabolites. Overall, the primary metabolite of serotonin, 5-hydroxyindoleacetic acid, appeared to be the most highly correlated with the individual obsessive-compulsive symptoms.

Clinical predictors of psychopathology in children and adolescents with Tourette Syndrome.

Tourette Syndrome (TS) is a neuropsychiatric disorder of childhood onset characterized by vocal and motor tics and associated psychopathologies. The current study was undertaken to explore the associations between tic symptomatology, related clinical variables and behavioral dysfunction within a cohort of TS subjects. Ninety-two child and adolescent TS subjects were rated through self-measure, and by parents on measures of tic symptomatology, OC characteristics, and dysfunctional behaviors including learning difficulties and attention deficits. Statistical modeling revealed associations among tic clusters, clinical items and behavioral measures, which were unique for the child and adolescent subgroups.

The course of tics in Tourette syndrome: a 5-year follow-up study.

The current study was undertaken to explore the course of tics in Gilles de la Tourette's syndrome (TS). As part of a prospective 5-year follow-up of non-clinically based TS subjects who had originally participated in a comprehensive research protocol, 23 subjects (ages 11 to 53 years) were reevaluated for tics and obsessive-compulsive (OC) characteristics. Three (13%) of the subjects had an improvement in total tic symptomatology, while 15 (65.2%) had no change and 5 (21.7%) worsened. Improvement or worsening was independent of baseline developmental age across child, adolescent, and adult subgroups. Complex motor tics at baseline predicted complex motor tics and simple phonic tics at follow-up. Baseline OC and complex motor tics independently predicted subsequent OC and complex motor symptoms. Data from the current study provide evidence of the stability of tic subtypes over time and developmental period.

Obsessive characteristics in subjects with Tourette's syndrome are related to symptoms in their parents.

The symptom characteristics of two Tourette's syndrome (TS) subgroups formed on the basis of their parents' obsessive-compulsive (OC) symptomatology were explored. TS subjects with parents having OC symptoms had significantly more OC symptoms and complex tics and a later age of symptom onset than the balance of the TS cohort. These findings suggest an association between parental OC symptoms and OC symptoms in their TS offspring.

Blood pressure and heart rate response of panic disorder patients receiving imipramine in a dose-response treatment paradigm.

This article reports the effects of imipramine on heart rate and blood pressure in panic disorder patients who participated in an 8-week double-blind dosage response treatment protocol. At the end of a placebo baseline, patients were randomly assigned to placebo or one of three weight-adjusted imipramine dosages: low (0.5 mg/kg per day), medium (1.5 mg/kg per day), or high (3.0 mg/kg per day). It was demonstrated that imipramine had no significant effect on sitting or standing diastolic or systolic blood pressure. Although there was a trend toward a systolic blood pressure drop with positional change, it did not reach statistical significance. There were no significant changes in diastolic blood pressure with postural change. Imipramine did increase sitting and standing heart rate without revealing a clear dosage correlation. In contrast to the pretreated state, the reflex heart rate response to postural change was significantly increased in the posttreatment state, also in a dosage-independent manner. Within the high-dose imipramine group, the baseline sitting to standing heart rate increase was significantly higher in those who dropped out because of drug side effects compared with those who remained. Evidence from this study suggests that imipramine has a dosage-independent effect on resting and reflex heart rate. Future studies should consider postural heart rate reactivity as a potential measure of intolerance to the side effects of high doses of imipramine.

Patterns of obsessive compulsive symptoms in Tourette subjects are independent of severity.

Studies have examined the expression of obsessive compulsive (OC) symptoms in obsessive compulsive disorder (OCD), OCD with co-occurring Tourette's Syndrome (TS) or chronic motor tic disorder (CMT) and TS alone. In adult samples, there appears to be a relatively consistent OC symptom thematic content that characterizes OCD alone and OCD in conjunction with tics or TS. Previous studies have controlled for the severity of OC symptoms in OCD and TS groups. In the current study, it was our objective to determine whether patterns of OC symptoms in TS are independent of OC symptom severity. The current exploratory study examined OC symptom expression in a nonclinically based TS sample with a broad range of OC symptoms and severity and a selected clinical OCD sample without TS/tics. Univariate and multivariate statistical analysis explored patterns of OC symptom expression between the two groups. Similar to previous reports examining OC symptoms in OCD and OCD with TS/tics, subjects with OCD alone were characterized by contamination obsessions and cleaning compulsions. In contrast, TS subjects had more somatic, sexual and symmetry obsessions and more checking, counting and touching/blinking compulsions, independent of OC symptom and tic severity. A discriminant function using obsessive items alone correctly grouped 91.4% of cases. The current study replicates patterns of OC symptom expression unique to OCD alone. Patterns of OC symptoms, in particular obsessive symptoms, can robustly predict membership in OCD or TS groups, even with a substantial variation in OC symptom severity as measured by the Y-BOCS score.

DSM-III personality disorders in generalized anxiety, panic/agoraphobia, and obsessive-compulsive disorders.

In an earlier report, we stated that personality profiles of patients with panic disorder/agoraphobia (n = 187) and obsessive-compulsive disorder ([ODC] n = 51) were similar, albeit more pronounced in OCD, suggesting that the link between panic disorder/agoraphobia and DSM-III personality disorders (PDs) or traits may be nonspecific. The present report extends the comparative study of DSM-III PDs/traits, as assessed by the Personality Diagnostic Questionnaire (PDQ), by adding a third diagnostic group of 39 patients with generalized anxiety disorder (GAD). The personality assessment of panic disorder/agoraphobia and GAD patients yielded virtually identical results on the PDQ and Eysenck Personality Inventory (EPI). Because GAD lacks the prominent panic, phobic, and obsessive-compulsive symptoms of other anxiety disorders, the present findings provide strong support for a nonspecific link between panic disorder/agoraphobia and DSM-III PDs/traits and for the presence of common personality characteristics in anxiety disorders.