Gary R. Gaffney

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 Childrens 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.

Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome.

OBJECTIVE To evaluate the efficacy and tolerability of risperidone in comparison with clonidine in the treatment of children and adolescents with Tourettes syndrome (TS). METHOD Following a 7- to 14-day single-blind, placebo lead-in, 21 subjects aged 7 to 17 years were randomly assigned to 8 weeks of double-blind treatment with clonidine or risperidone. Research scales evaluated tics and comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms. RESULTS Risperidone and clonidine appeared equally effective in the treatment of tics in an intent-to-treat analysis, as rated by the Yale Global Tic Severity Scale (YGTSS). Risperidone produced a mean reduction in the YGTSS of 21%; clonidine produced a 26% reduction. Among subjects with comorbid obsessive-compulsive symptoms, 63% of the risperidone group and 33% of the clonidine group responded to treatment (not significant). The most common adverse event seen with both treatments was sedation, which was mild to moderate in severity. Sedation subsequently resolved with continued administration of the medication or with a dose reduction. No clinically significant extrapyramidal symptoms were observed. CONCLUSIONS In this pilot study, risperidone demonstrated efficacy equivalent to clonidine in the treatment of tic symptoms in children and adolescents with TS. Further research is needed to clarify the role of atypical antipsychotics in TS and to delineate potential benefits for comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms.

SPECT brain imaging abnormalities in attention deficit hyperactivity disorder.

SPECT using N-Isopropyl I-123 IMP was performed, as part of a neuropsychiatric evaluation, on 10 patients with the DSM III-R diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) and 6 patients from a non-ADHD mixed psychiatric group used as controls for comparison. Mean regional I-123 IMP SPECT region of interest (ROI) count ratios (left to right) demonstrated that the ADHD patients had greater overall hemispheric I-123 IMP uptake asymmetry with less activity in the left frontal and left parietal regions in comparison to control patients. Both groups demonstrated similar I-123 IMP uptake asymmetry in the temporal regions. These findings are consistent with previous studies of brain physiology in ADHD implicating regional cortical perfusion and metabolism abnormalities in areas which are involved in the control of attentional processes.

Morphological evidence for brainstem involvement in infantile autism

Previous neurophysiological and neuroanatomic studies suggest brainstem dysfunction in infantile autism. Therefore, we investigated the brainstem structure of autistic patients by planimetric analysis of midsagittal magnetic resonance imaging scans. We found the entire brainstem and one component--the pons--to be statistically significantly smaller in the autistic group when compared with medical controls. We also noted no correlation between brainstem size and age in the autistic group--a correlation that was found in the control group. These data present morphological evidence of brainstem involvement in the infantile autism syndrome.

Bupropion SR vs. Methylphenidate vs. Placebo for Attention Deficit Hyperactivity Disorder in Adults

Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV) subjects (18–60 years old) were randomized to bupropion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and verbal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed.

Forebrain Structure in Infantile Autism

Researchers implicate central nervous system dysfunction in infantile autism, but postmortem examinations and in vivo brain imaging studies have produced conflicting results concerning the neuronal systems involved. Magnetic resonance imaging--a new modality of in vivo brain imaging--was used to investigate the cerebral and thalamic structure of 105 autistic patients. Compared with the control group, there was an overall difference in the forebrain morphology of the autistic subjects due to subtle but statistically significant differences in the anterior ventricular horns, lateral ventricles, and the right lenticular nucleus. These results, when considered with previous studies of cerebral structure, suggest that there are subtle alterations in the forebrain of autistic patients.

Lymphocyte subsets and interleukin-2 receptors in autistic children.

Blood samples were obtained from 10 male autistic children ages 7–15 years and 10 age-matched, male, healthy controls. Lymphocyte subsets (helper-inducer, suppressor-cytotoxic, total T, and total B cells) were enumerated using monoclonal antibodies and flow cytometry. Bound and soluble interleukin-2 receptors were assayed in unstimulated blood samples and in cell cultures following 72-hour stimulation with phytohemagglutinin. The children with autism had a lower percentage of helper-inducer cells and a lower helpersuppressor ratio, with both measures inversely related to the severity of autistic symptoms (r=−.56 and −.68, respectively). A lower percentage of lymphocytes expressing bound interleukin-2 receptors following mitogenic stimulation was also noted, and this too was inversely related to the seventy of autistic symptoms.

Neuroimaging in child and adolescent psychiatry.

Although less well studied in child and adolescent psychiatry than in adult psychiatry, brain imaging has significantly altered psychiatric research and practice. This review focuses on the modalities that are used to image the brain. These include structural imaging techniques of computer tomography (CT) and magnetic resonance imaging (MRI), as well as functional imaging techniques of computed electroencephalography (CEEG), positron emission tomography (PET), and single photon emission computed tomography (SPECT). The technologies are reviewed, strengths and weaknesses of modalities discussed, and research progress reported.

Tc-99m HMPAO SPECT brain imaging of Gilles de la Tourette's syndrome

Gilles de la Tourettes syndrome is a complex neuropsychiatric disorder. Its onset is characteristically during childhood and it is manifested by the ongoing presence of multiple motor and vocal tics. Additional disturbances that may be evident include attention deficit, obsessive compulsive and manic depressive symptoms, as well as learning disorders. Although CT and MRI structural brain studies reveal no consistent abnormalities in patients with Tourettes syndrome, the use of PET imaging has suggested that regional CNS physiologic aberrations can be identified in this condition. In this report, the use of Tc-99m HMPAO SPECT in an 11-year-old girl with Tourettes syndrome demonstrates hypoperfusion in the left basal ganglial region

Panic attacks in families of patients with mitral valve prolapse

One explanation for the association between mitral valve prolapse (MVP) and panic attacks in clinic populations is that panic attacks represent a set of symptoms caused by mitral prolapse. Since mitral prolapse is often familial, this hypothesis predicts a higher incidence of panic attacks in relatives of persons with prolapse than the general population and the incidence of panic attacks in the relatives should be independent of panic attacks in the proband. We interviewed 50 probands with mitral prolapse and obtained family history data on panic attacks in their first degree relatives. The incidence of panic attacks in these relatives was 4.5 +/- 1.4% which is consistent with control rates which we have reported in previous studies. Twelve MVP probands also had panic attacks. The incidence of panic attacks in their relatives (15.7 +/- 5.1%) was significantly higher than the rate found among relatives of 38 probands without panic attacks (1.2 +/- 0.8%). These findings are consistent with the hypothesis that mitral prolapse and panic attacks are segregating independently in these families.