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Biomedical subjects

M A Riddle

Publications and source records attributed to M A Riddle.

At least 37 records · Page 2Linked to original sources
PubMed1999

Critical review of tricyclic antidepressant use in children and adolescents.

OBJECTIVE: To provide a critical review of the role of tricyclic antidepressant (TCA) medications in children and adolescents. METHOD: Multiple resources including a Medline search (1966-1998) were used. RESULTS: There were few double-blind, placebo-controlled studies of TCAs, and even fewer with positive results. Also, potentially serious cardiovascular side effects have been described. CONCLUSIONS: The future therapeutic role of TCAs for children and adolescents needs to be seriously weighed against lethality of overdose, the unresolved issue of possible sudden unexplained death, and the availability of safer and easier to monitor medications. Ongoing future research on heart rate variability and epidemiology of psychotropic medication-related deaths will address developmental aspects of TCA use.

Adolescent↗
PubMed1999

Anxiolytics, adrenergic agents, and naltrexone.

OBJECTIVE: To review extant data on the efficacy and safety of anxiolytic medications (benzodiazepines, buspirone, and other serotonin 1A agonists), adrenergic agents (beta-blockers and alpha 2-adrenergic agonists clonidine and guanfacine), and the opiate antagonist naltrexone that have been used to treat various psychopathologies in children and adolescents. To identify critical gaps in our current knowledge about these agents and needs for further research. METHOD: All available controlled trials of these medications in children and adolescents published in English through 1997 were reviewed. In addition, selected uncontrolled studies are included. RESULTS: The major finding, that there are virtually no controlled data that support the efficacy of most of these drugs for the treatment of psychiatric disorders in children and adolescents, is both surprising and unfortunate. For some drugs, e.g., buspirone and guanfacine, this is because no controlled studies have been carried out in children and/or adolescents. For other drugs, e.g., clonidine and naltrexone, most of the placebo-controlled studies have failed to demonstrate efficacy. CONCLUSIONS: The strongest recommendations for controlled studies of safety and efficacy in children and adolescents can be given for the following drugs: benzodiazepines for acute anxiety; buspirone (and newer serotonin 1A agonists as they become available) for anxiety and depression; beta-blockers for aggressive dyscontrol; guanfacine for attention-deficit/hyperactivity disorder; and naltrexone for hyperactivity, inattention, and aggression in autistic disorder.

Adolescent↗
PubMed1999

Pharmacotherapy in children and adolescents with obsessive-compulsive disorder.

This article examines the general principles of psychopharmacologic treatment of obsessive-compulsive disorder (OCD) in children and adolescents. It includes a description of the currently approved medications for the treatment of children and adolescents with OCD, their side effect profiles, approaches to refractory OCD, and a discussion of drug interactions. Future directions for research are also considered.

Adolescent↗
PubMed1998

The new antidepressants. Selective serotonin reuptake inhibitors.

This article provides a resource for choosing among available SSRIs to treat pediatric patients. SSRIs are addressed according to five areas of interest: treatment efficacy data, untoward effects profile, pharmacokinetic characteristics, potential drug-drug interactions, and cost. Strategies for SSRI dosing and pretreatment work-up are also discussed. Included in the article is a reference table for SSRI dosing, available preparations, and cost per dose. Also included is an abbreviated reference table of important cytochrome P-450 isoenzymes, isoenzyme inhibition by SSRIs, and selected psychotropic and somatic medication substrates.

Adolescent↗
PubMed1998

Prevalence variations in psychotropic treatment of children.

This study was undertaken to clarify several aspects of the estimation of prevalence of three commonly use pediatric psychotropic agents, namely, methylphenidate, desipramine, and imipramine. The study aims are threefold: (1) to show the variability of drug prevalence by comparing estimates from three data sources; (2) to show the misleading impression that can be created by reporting drug prevalence estimates based on counts of prescriptions rather than persons; (3) to show the utility of gender-by-age-specific prevalence of drug use as a marker for diagnosis. Two data sources that yield population-based prescription estimates were available: 1991 Medicaid administrative claims data for prescriptions from a mid-Atlantic state and 1991 prescription records of the northwest region of Kaiser Permanente, a staff-model health maintenance organization (HMO). Another source of data consists of the 1991 National Ambulatory Medical Care Survey, which records medication information reported during physician office visits. Data analysis consists of quantitative estimates of (1) drug prevalence from each source; (2) the ratio of prescription claims to persons; and (3) the proportion of drug use according to age and gender. Methylphenidate and desipramine prevalence had a twofold greater use among state Medicaid enrollees compared with HMO enrollees. Average claims-to-person ratios of 5:1 suggest better accuracy using persons with medication rather than prescription counts. Gender-by-age-specific prevalence rates showed that 75% of the drug use for desipramine among those less than 15 years old was found among males, whereas 75% of the desipramine use among those 15 or older was found among females, suggesting its use for the treatment of attention deficit-hyperactivity disorder among young males and for depression among older females. The variability of community physician decision making in pediatric psychopharmacology is better understood by observing drug prevalence rates from different settings. National sampling efforts should be undertaken to verify regional and setting-specific prevalence findings and to learn the reasons for their fluctuation.

Adult↗
PubMed1998

Racial disparity in psychotropic medications prescribed for youths with Medicaid insurance in Maryland.

DESIGN: A retrospective analysis was conducted using state Medicaid prescription drug reimbursement claims for youths aged 5 through 14 years according to the race of the recipients of psychotropic and medical drugs. METHOD: A person-based data set was created from Medicaid administrative data for fiscal year 1991 from the state of Maryland to yield the following: (1) estimates of prevalence of prescription recipients per 100 eligible enrollees; (2) relative prescription use ratios according to race (African-American versus Caucasian); and (3) the interrelation of race and geographic region on prescription prevalence. RESULTS: Five major findings were observed: (1) African-American youths with Medicaid insurance aged 5 through 14 were less than half (39% to 52%) as likely to have been prescribed psychotropic medications as Caucasian youths with Medicaid insurance; (2) the relative difference for nonpsychotropic medication classes was much less pronounced: African-American youths were prescribed nonpsychotropic medications at a rate 60% to 87% of the Caucasian youths' rate; (3) the stimulants (essentially methylphenidate) had the most disparate African-American/Caucasian ratio (1:2.5); (4) the racial disparity for psychotropics was not altered by partial (noncontinuous enrollment) eligibility status; and (5) although geographic variation reduced the racial disparity, the substantial racial difference (1:2.0) remained. CONCLUSION: Compared with Caucasians, African-American youths aged 5 through 14 with Medicaid insurance coverage showed a distinctly lower rate of treatment with psychopharmacological agents.

Adolescent↗
PubMed1997

Fluoxetine has no marked effect on tic symptoms in patients with Tourette's syndrome: a double-blind placebo-controlled study.

To evaluate the efficacy of fluoxetine in the treatment of tics and obsessive-compulsive symptoms in patients with Tourette's syndrome (TS), 14 subjects (8-33 years old) with TS participated in a 20-week, fixed-dose (20 mg daily), double-blind, placebo-controlled crossover trial of fluoxetine monotherapy. Five subjects met criteria for obsessive-compulsive disorder (OCD), 6 additional subjects had obsessive-compulsive features, and 3 subjects had TS without obsessive-compulsive symptoms. There was no improvement in tics after 8 weeks of treatment with fluoxetine (p = 0.58). In contrast, fluoxetine treatment was associated with a significant reduction in obsessive-compulsive symptoms for the group of 6 subjects initially randomized to fluoxetine (p = 0.04). Crossover analysis showed that fluoxetine had no marked effect on tics (n = 10, p = 0.30, but produced a modest decrease in obsessive-compulsive symptoms (n = 8, p = 0.06). Order effects and carry-over effects were not significant. Withdrawal to placebo was associated with a 55% increase in obsessive-compulsive symptoms (p = 0.05), but there was no effect on tics. The most common side effect was transient behavioral activation, which occurred in about half of the subjects and was more common in children. Fluoxetine may be useful for the treatment of obsessive-compulsive symptoms in some patients with TS, but does not appear to be effective for tics.

Adolescent↗
PubMed1997

Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity.

OBJECTIVE: To evaluate the reliability and validity of a semistructured measure of obsessive-compulsive symptom severity in children and adolescents with obsessive-compulsive disorder (OCD). METHOD: Sixty-five children with OCD (25 girls and 40 boys, aged 8 to 17 years) were assessed with the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Interrater agreement was assessed by four raters in a subsample (n = 24). Discriminant and convergent validity were assessed by comparing CY-BOCS scores to self-ratings of depression, anxiety, and obsessive-compulsive symptoms. RESULTS: Internal consistency was high, measuring .87 for the 10 items. The intraclass correlations for the CY-BOCS Total, Obsession, and Compulsion scores were .84, .91, and .68, suggesting good to excellent interrater agreement for subscale and total scores. The CY-BOCS Total score showed a significantly higher correlation with a self-report of obsessive-compulsive symptoms (r = .62 for the Leyton survey) compared with the Children's Depression Inventory (r = .34) and the Children's Manifest Anxiety Scale (r = .37) (p = .02 and .05, respectively). CONCLUSIONS: The CY-BOCS yields reliable and valid subscale and total scores for obsessive-compulsive symptom severity in children and adolescents with OCD. Reliability and validity appear to be influenced by age of the child and the hazards associated with integrating data from parental and patient sources.

Adolescent↗
PubMed1997

Methylphenidate patterns among Medicaid youths.

Treatment of attentional disorders in America has increased dramatically in recent years. This trend is accounted for partly by lengthening the duration of treatment into adulthood for some individuals as well as by increased treatment among girls. Beyond these factors, the role of economic status, race, and geographic region to explain the variation in methylphenidate use is not well understood. Computerized administrative data were used to explore the influence of several sociodemographic factors on the prevalence of methylphenidate use. The data source consisted of Maryland Medicaid prescription drug reimbursement claims data for FY1991 for children ages 5 to 14 years. In effect, the study was restricted to a sample of patients with limited income. The study aims included (1) measuring gender-, age-, race-, and region-specific methylphenidate prevalence for this restricted income population; (2) comparing the Caucasian:African-American (C:A-A) ratio for methylphenidate with the C:A-A ratio for several drug therapies having non-psychotropic uses, specifically the anti-asthma drug, theophylline, and antibiotics for infections; and (3) estimating the average daily dose of methylphenidate from prescription claims data. Total drug-specific prevalence among the 5-14 year olds was 2.2 percent for methylphenidate while age-specific prevalence varied from 0.4 percent (5 year olds) to 3.4 percent (9 year olds). The gender ratio was 3.7:1 (M:F), confirming the increasing trend for girls to receive this medication. Substantial variation across eight defined regions of the state was observed. Racial differences were pronounced: African-Americans were 2.5 times less likely to receive methylphenidate than Caucasian youths. As hypothesized, non-psychotropic drug use was distinctly different from psychotropic drug use in terms of race: theophylline was 1.5 times more likely to be found for African-Americans than Caucasians, whereas antibiotic prescriptions were 1.5 times more likely to be prescribed to Caucasian youths. Average daily dose of methylphenidate was estimated to be 18.7 +/- 10.4 mg for 5-9 year olds and 26.8 +/- 14.0 mg for 10-14 year olds. This brief report confirms the typically lower rate among African-American Medicaid youths for most prescription drugs. The dramatic racial disparity for the psychotropic agent methylphenidate is a new and compelling finding which should be verified among other economic groups. Diagnostic, referral, and cultural bias should be ruled out as possible explanations for the observed differences.

Adolescent↗
PubMed1996

Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance.

To investigate the transmission of Tourette syndrome (TS) and associated disorders within families, complex segregation analysis was performed on family study data obtained from 53 independently ascertained children and adolescents with TS and their 154 first-degree relatives. The results suggest that the susceptibility for TS is conveyed by a major locus in combination with a multifactorial background. Other models of inheritance were definitively rejected, including strictly polygenic models, all single major locus models, and mixed models with dominant and recessive major loci. The frequency of the TS susceptibility allele was estimated to be .01. The major locus accounts for over half of the phenotypic variance for TS, whereas the multifactorial background accounts for approximately 40% of phenotypic variance. Penetrance estimates suggest that all individuals homozygous for the susceptibility allele at the major locus are affected, whereas only 2.2% of males and 0.3% of females heterozygous at the major locus are affected. Of individuals affected with TS, approximately 62% are heterozygous and approximately 38% are homozygous at the major locus. While none of the families had two parents affected with TS, 19% of families had two parents affected with the broader, phenotype, which includes TS, chronic tic disorder, or obsessive-compulsive disorder.

Adolescent↗
PubMed1995

Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls.

To examine the role of noradrenergic, dopaminergic, and serotonergic mechanisms in the pathobiology of obsessive compulsive disorder (OCD) and Tourette's syndrome (TS), concentrations of tyrosine (TYR), norepinephrine (NE), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA), tryptophan (TRP), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the lumbar cerebrospinal fluid (CSF) of 39 medication-free OCD patients, 33 medication-free TS patients, and 44 healthy volunteers. CSF TYR concentrations were reduced (p < .05) in the OCD patients compared to the healthy subjects. CSF NE in TS patients was 55% higher than in healthy controls (p < .001) and 35% higher than in OCD patients (p < .001). After covarying for height, CSF HVA levels were reduced (p < .05) in the OCD group compared to TS patients but not compared to the normal volunteers. No mean differences in CSF MHPG, TRP, and 5-HIAA were observed in this study across the three groups. The CSF NE data support the hypothesis that noradrenergic mechanisms are involved in the pathobiology of TS. Alterations in the balance of noradrenergic, dopaminergic, and serotonergic systems are likely involved in the pathobiology of OCD.

Adolescent↗
PubMed1995

Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: preliminary clinical experience.

OBJECTIVE: Many children with Tourette's syndrome (TS) are handicapped more by difficulties with inattention, impulsivity, and hyperactivity than by their tics. However, stimulant medications used to treat attention-deficit hyperactivity disorder (ADHD) can exacerbate tics. Guanfacine is an alpha 2-adrenergic agonist that may have beneficial effects on attention, without the hypotensive or sedative effects of clonidine, which is often used as an alternative to stimulants. METHOD: An open-label study of guanfacine was performed in 10 children with TS+ADHD, aged 8 to 16 years. The duration of follow-up was 4 to 20 weeks, and the majority of subjects were treated with 1.5 mg/day. Ratings of tic severity and ADHD symptoms were obtained using the Yale Global Tic Severity Scale (YGTSS), the Tic Symptom Self Report (TSSR), and the Conners Parent Rating Scale. In addition, blind Continuous Performance Tests (CPTs) were performed at baseline and at two follow-up intervals in eight subjects. RESULTS: Guanfacine was associated with significant decreases in both commission errors (p < .02) and omission errors (p < .01) on the CPT. In addition, guanfacine caused a significant decrease in severity of motor (p < .02) and phonic (p < .02) tics as measured by the TSSR and the YGTSS, respectively. The most common side effects were transient sedation and headaches. CONCLUSION: Guanfacine may provide a safe alternative therapy for children with ADHD in the presence of tics. Future double-blind, controlled trials should be undertaken.

Adolescent↗
PubMed1995

Childhood trichotillomania: clinical phenomenology, comorbidity, and family genetics.

OBJECTIVE: DSM-IV defines trichotillomania as an impulse disorder with rising tension followed by relief or gratification. Alternative formulations view trichotillomania as an internalizing disorder or variant of obsessive-compulsive disorder (OCD). This study addresses this controversy by examining the phenomenology, comorbidity, and family genetics of childhood trichotillomania. METHOD: Fifteen chronic hair-pullers (13 girls), aged 9 through 17 years (mean 12.3 +/- 2.3 years), were systematically assessed. Child Behavior Checklist (CBCL) profiles of the hair-pulling girls were compared with those of 37 girls from a general child psychiatry clinic and of 15 girls with OCD. RESULTS: All the hair-pullers had impairing cosmetic disfigurement; however, 4 subjects (26.7%) denied rising tension or relief. All three groups had comparable global CBCL problem scores. The CBCL symptom profile of the hair-pulling group differed significantly from that of the general clinic group but strongly resembled that of the OCD group. The hair-pulling group, however, had few obsessions or compulsions aside from hair-pulling; two (13%) subjects met criteria for OCD. As a group, hair-pulling subjects had substantial comorbid psychopathology, and a parental history of tics, habits, or obsessive-compulsive symptoms was common. CONCLUSIONS: These findings lend only partial support to the notion of trichotillomania as an OCD-spectrum disorder. Rising tension followed by relief or gratification may not be an appropriate diagnostic criterion for trichotillomania.

Adolescent↗
PubMed1995

Disruptive behavior, hyperactivity, and learning disabilities in children with Tourette's syndrome.

As in many other areas of science, improvements in research methodologies lead the way to powerful new understanding of disorders and their treatment. Great strides have been made in defining the phenomenology of TS and its relationship to other disorders. However, we have not yet reached a true consensus and developed treatment strategies based on that consensus. Clearly much research needs to be done. Identifying the putative gene for TS would greatly accelerate this process.

Adolescent↗
PubMed1994

Elevated cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder. Comparison with Tourette's syndrome and healthy controls.

BACKGROUND: Limited neurobiological data have implicated central arginine vasopressin in the pathobiology of obsessive-compulsive disorder (OCD). Based on twin, family genetic, and pharmacological studies, some forms of OCD are etiologically related to Tourette's syndrome. The role of arginine vasopressin and related compounds such as oxytocin in Tourette's syndrome has not been previously explored. METHODS: To compare cerebrospinal fluid (CSF) levels of arginine vasopressin and oxytocin, we collected CSF at midday in a standardized fashion from a total of 83 individuals (29 patients with OCD, 23 patients with Tourette's syndrome, and 31 normal controls). We also collected family study data on each subject to determine which subjects had a family history positive for Tourette's syndrome, OCD, or related syndromes. RESULTS: In contrast to previous reports, we report similar concentrations of arginine vasopressin for all three groups but increased oxytocin levels in patients with OCD. Remarkably, this increase was observed only in a subset of patients with OCD (n = 22) independently identified as being without a personal or family history of tic disorders (P = .0003). In this subgroup of patients, the CSF oxytocin level was correlated with current severity of OCD (n = 19, r = .47, P < .05). CONCLUSIONS: A possible role for oxytocin in the neurobiology of a subtype of OCD is suggested by the elevated CSF levels of oxytocin and by the correlation between CSF oxytocin levels and OCD severity. These findings reinforce the value of family genetic data in identifying biologically homogeneous (and perhaps more etiologically homogeneous) groups of patients with OCD. Together with emerging pharmacological data showing differential responsiveness to treatment of tic-related OCD vs non-tic-related OCD, these data also argue strongly for the incorporation of tic-relatedness as a variable in biological and behavioral studies of patients with OCD.

Adolescent↗
PubMed1994

Abnormal magnetic resonance imaging T2 relaxation time asymmetries in Tourette's syndrome.

Recent imaging studies in Tourette's syndrome (TS) have reported a loss of normal asymmetry in basal ganglia volumes. Our recent report of reduced midline sagittal cross-sectional area in TS suggests that altered lateralization may be widespread throughout the TS cerebrum. We report here our analyses of cerebral asymmetries of T2 (transverse or spin-spin) relaxation times derived from multi-echo/multi-planar/spin-echo magnetic resonance images in 14 adult TS subjects and 14 matched normal control subjects. T2 relaxation times were found to be asymmetric throughout the cerebrum of normal control subjects, with differences seen between T2 times of corresponding regions of both cerebral hemispheres that were small in magnitude (2-5%) but of a high degree of statistical significance in all regions examined. Our hypothesis of altered T2 relaxation time asymmetries in TS was confirmed in a multivariate analysis of variance, with post hoc analyses suggesting that group differences were attributable to specific asymmetry differences in the TS insular cortex and frontal white matter. Exploratory analyses revealed group differences in T2 times of the amygdala and red nucleus, as well as significantly lower ferritin levels in the TS group. These findings are discussed in relation to the previous TS volumetric studies, and the tissue characteristics that might produce normal and abnormal relaxation time asymmetries are considered.

Adolescent↗