Biomedical subjects

Eric Hollander

Publications and source records attributed to Eric Hollander.

At least 37 records · Page 2Linked to original sources

PubMed2006

Selective serotonin reuptake inhibitors in autism: a review of efficacy and tolerability.

BACKGROUND: Awareness of the impact and prevalence of autism spectrum disorders has significantly increased in recent years. Given the dearth of reliable interventions, there is great interest in demonstrating efficacy of the various treatment options. A growing body of evidence links autism spectrum disorders to abnormalities in serotonin function, and the selective serotonin reuptake inhibitors (SSRIs) have been utilized to target various symptoms of the disorders. This article reviews the available data on the efficacy and tolerability of SSRIs in individuals with autism spectrum disorders. Objectives for future research in this area will also be suggested. DATA SOURCES AND STUDY SELECTION: The entire PubMed database including MEDLINE (1966-July 2005) was searched for English-language biomedical articles. Search terms included autism, autism spectrum disorder, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, pervasive developmental disorder, selective serotonin reuptake inhibitors, and sertraline. All clinical trials evaluating treatment outcomes associated with the use of SSRIs in managing symptoms of autism that were identified in the search were reviewed. All randomized controlled trials and open-label trials were included in this review. Case reports and case series were excluded. DATA SYNTHESIS: We identified 3 randomized controlled trials and 10 open-label trials or retrospective chart reviews on the use of SSRIs in autism and autism spectrum disorders. The SSRIs that have been studied in autism spectrum disorders are citalopram, escitalopram, fluoxetine, fluvoxamine, and sertraline. Most studies demonstrate significant improvement in global functioning and in symptoms associated with anxiety and repetitive behaviors. While side effects were generally considered to be mild, increased activation and agitation occurred in some subjects. CONCLUSIONS: Although SSRIs may demonstrate therapeutic benefit in autism spectrum disorders, methodological weaknesses of many of the clinical trials suggest the need for additional randomized controlled trials. Furthermore, given the increased awareness of the dangers associated with SSRI-induced activation and agitation, the presence of these side effects in the autistic population warrants closer attention to dosage, titration, and subject selection issues.

Adolescent↗

PubMed2006

Serotonin-norepinephrine reuptake inhibitors in the treatment of obsessive-compulsive disorder: A critical review.

OBJECTIVE: To critically review the antiobsessional properties of serotonin-norepinephrine reuptake inhibitors (SNRIs) (venlafaxine and clomipramine) in the treatment of obsessive-compulsive disorder (OCD) as an alternative to selective serotonin reuptake inhibitors (SSRIs), which are currently considered the first-line treatment of OCD. DATA SOURCES: A MEDLINE search was performed to identify clinical trials with the SNRIs venlafaxine and clomipramine published from 1996 to 2004 (keywords: SNRIs, venlafaxine, duloxetine, and clomipramine, each matched individually with the term OCD), focusing on the best-designed studies for inclusion. DATA SYNTHESIS: Much of the literature about SNRIs in OCD supports the efficacy of these compounds in the treatment of OCD. However, double-blind, placebo-controlled studies with venlafaxine are lacking, and the most relevant studies consist of active comparison trials between SNRIs and SSRIs. In these studies, SNRIs seem to be as effective as SSRIs in OCD; SNRIs might be preferred for patients with certain types of treatment-resistant OCD or those with particular comorbid conditions. A large number of placebo-controlled and active comparison trials with clomipramine document efficacy in OCD, and meta-analytic studies suggest a small superiority over SSRIs. Compared with clomipramine, the SNRI venlafaxine showed fewer side effects and better tolerability. CONCLUSION: The SNRIs may represent a valid alternative to the SSRIs, particularly in specific cases. Double-blind, placebo-controlled studies are, however, needed to confirm the positive findings reported by several studies with venlafaxine.

Adrenergic Uptake Inhibitors↗

PubMed2006

A double-blind study of citalopram versus placebo in the treatment of compulsive sexual behaviors in gay and bisexual men.

OBJECTIVE: Compulsive sexual behavior (CSB) is a condition characterized by loss of control over sexual behavior and repeated negative consequences, including unsafe sex. Selective serotonin reuptake inhibitors have been found to reduce CSB symptomatology in open-label trials. The objective of this study was to conduct a preliminary double-blind, placebo-controlled evaluation of the efficacy, acceptability, and tolerability of citalopram in the treatment of CSB. METHOD: Twenty-eight men who have sex with men who met the threshold for CSB on the basis of existing validated measures participated in a 12-week, double-blind trial of citalopram 20 to 60 mg/day to evaluate its effects on CSB symptoms. The primary efficacy measure was the Yale-Brown Obsessive Compulsive Scale-Compulsive Sexual Behavior. The study was conducted from June 2002 to April 2004. RESULTS: Significant treatment effects were obtained for sexual desire/drive (p < .05) and frequency of masturbation (p < .01) and pornography use (p < .05). Both groups reduced sexual risk, but did not differ significantly. CONCLUSIONS: This study provides partial support for the effectiveness of citalopram for reducing symptoms of CSB in this population. Larger-scale trials are recommended to determine the public health benefits of this treatment.

Adult↗

PubMed2005

Comorbidity issues in the pharmacological treatment of Pathological Gambling: a critical review.

BACKGROUND: Pathological Gambling (PG) is an impulse control disorder often comorbid with other psychopathology, particularly bipolar spectrum disorders, attention deficit/hyperactivity disorder, obsessive-compulsive disorder (OCD) and substance abuse. This paper reviews the published literature on the pharmacological management of PG, highlighting how clinical and subclinical comorbid psychopathology influences the choice of pharmacological treatment. METHODS: Using Medline, the authors reviewed relevant articles published on this topic from 1995 to 2005, focusing on the best-designed studies for inclusion. RESULTS: Much of the literature on PG-treatment presupposes different theories regarding this disorder. Data suggest the utility of differentiating the pharmacotherapy of pathological gamblers in light of their comorbid profile, specifically assessing for comorbid bipolar, ADHD, OCD, and substance abuse disorders. CONCLUSION: Decisions about pharmacological treatment of PG should take into account current and previous comorbid disorders which influence treatment selection.

Journal Article↗

PubMed2005

Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder.

Autism is a neurodevelopmental disorder characterized by impairment in three core symptom domains: socialization, communication, and repetitive/stereotyped behaviours. Other associated symptom domains are also affected including impulsivity/aggression, self-injury, anxiety, and mood lability. Divalproex has been shown to have efficacy in treating epilepsy, bipolar disorder, mood lability, and impulsive aggression. The present study evaluated the use of divalproex in the treatment of repetitive, compulsive-like symptoms of autism spectrum disorder (ASD). Thirteen individuals with ASD participated in an 8-wk, double-blind, placebo-controlled trial of divalproex sodium vs. placebo. There was a significant group difference on improvement in repetitive behaviours as measured by the Children's Yale-Brown Obsessive Compulsive Scale (C-YBOCS) (p=0.037) and a large effect size (d=1.616). This study provides preliminary support for the use of divalproex in treating repetitive behaviours in ASD. Further research is needed to evaluate the specificity and mechanism of action of these findings.

Adolescent↗

PubMed2005

Striatal volume on magnetic resonance imaging and repetitive behaviors in autism.

BACKGROUND: The repetitive behaviors seen in autism phenotypically resemble those seen in obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), disorders in which structural and functional abnormalities of the basal ganglia (BG) are present and correspond to the severity of repetitive behaviors. METHODS: Seventeen subjects with autism by DSM-IV and Autism Diagnostic Interview (ADI) and 17 matched controls completed a 1.5 T magnetic resonance image (MRI) of the brain. Two blinded researchers, with good inter-rater reliability, outlined the right and left caudate and putamen. Autistic and control BG volumes covaried for total brain volume were compared using analysis of covariance. BG volumes within the autistic group were correlated with the ADI Repetitive Behavior scores (ADI-C domain). RESULTS: Right caudate volume controlled for total brain volume was significantly larger in autistic subjects than in controls. In addition, right caudate and total putamen volumes correlated positively with repetitive behavior scores on the ADI-C domain, particularly the higher order OCD-like repetitive behaviors. CONCLUSIONS: Increased right caudate volume in autism is of interest, since this has also been observed in OCD patients. Increased volume of the right caudate and total putamen positively correlated with greater repetitive behaviors, supporting the hypothesis of BG dysfunction associated with repetitive behaviors in autistic adults.

Adolescent↗

PubMed2005

Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses.

BACKGROUND: Neurons in the basal ganglia are connected to areas of prefrontal cerebral cortex involved in higher cognitive functions, and these connections occur primarily via the thalamus. In patients with bipolar disorder, regardless of age, neuroimaging studies have consistently reported an increased number of white matter hyperintensities, indicating possible alterations in striatum-thalamus and thalamus-prefrontal cortex connections. METHODS: In the current study, we acquired high-resolution magnetic resonance imaging (MRI) and diffusion tensor (DT) scans of 40 patients with bipolar spectrum (BPS) illnesses (bipolar type I = 17, bipolar type II = 7, cyclothymia = 16) and 36 sex- and age-matched control subjects. Two researchers, without knowledge of diagnosis, outlined the caudate, putamen, and thalamus on contiguous axial MRI slices. We measured the volumes of the basal ganglia, thalamus, and gray/white matter of the frontal cortex. RESULTS: Bipolar spectrum patients as a single group did not differ from control subjects in thalamus and the basal ganglia volumes, but the cyclothymia patients had reductions in the volumes of putamen and the thalamus compared with control subjects. The BPS patients had significantly reduced volume of the white and the gray matter of the frontal cortex. Furthermore, compared with control subjects, BPS patients as a group showed alterations in anisotropy of the internal capsule adjacent to the striatum and thalamus and the frontal white matter. CONCLUSIONS: Our findings indicate that BPS patients may have distinct anatomical alterations in brain structures involved in the regulation of mood and cognition, as well as alterations in these structures' connection to related brain areas.

Adult↗

PubMed2005

Pharmacological treatments of pathological gambling.

Medication treatment studies have demonstrated short-term efficacy of various SRIs, opioid antagonists, and mood stabilizers in sub-samples of adult treatment seeking pathological gamblers. Pathological gambling is frequently comorbid with bipolar spectrum disorders, substance abuse/dependence, and attention-deficit/hyperactivity disorder (ADHD), and comorbidity may influence treatment response in pathological gambling. This review focuses on recent research examining the treatment of pathological gambling and highlights methodological challenges for future studies.

Antidepressive Agents, Second-Generation↗

PubMed2005

Reliability and validity of the pathological gambling adaptation of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS).

The Yale Brown Obsessive Compulsive Scale adapted for Pathological Gambling (PG-YBOCS) was developed to measure the severity and change in severity of pathological gambling symptoms. The PG-YBOCS is a 10-item clinician-administered questionnaire that measures the severity of PG over a recent time interval (usually within the past one/two week(s)). In order to assess and validate the scale, it was administered to 337 subjects: 188 pathological gamblers and 149 healthy controls. Internal consistency and correlations between individual items and total score were assessed for various permutations of the sample. Other scales were administered to assess convergent, discriminant and content validity. Sensitivity to change was evaluated in treatment studies with fluovoxamine, lithium, and valproate. Each item was frequently endorsed across a range of severity. Good inter-rater reliability and internal consistency were obtained. The PG-YBOCS showed high validity and reliability for total score, item-total correlations, and for each subscale (Thoughts/Urges and Behavior). PG-YBOCS scores correlated with global severity and South Oaks Gambling Screen (SOGS) scores. The scale was also sensitive to change in pathological gambling severity. PG-YBOCS thus appears to be a reliable and valid measure of pathological gambling severity, and can be regarded as an important tool for clinicians and researchers treating pathological gamblers.

Adult↗

PubMed2005

Brain stimulation techniques in the treatment of obsessive-compulsive disorder: current and future directions.

Recent studies on the epidemiology of obsessive-compulsive disorder (OCD) estimate 50 million patients suffer from OCD worldwide, thus making it a global problem. The treatment of OCD has changed substantially over the last 2 decades following the introduction of selective serotonin reuptake inhibitors, which provide symptom improvement in approximately 60% of patients. However, some patients remain resistant to the standard pharmacologic and behavioral treatments. Although some treatment-resistant patients respond to pharmacologic augmentations, others do not, and there is evidence that some of the most severe cases benefit from treatment with neurosurgical interventions. Besides pharmacologic, behavioral, and neurosurgical approaches, different brain stimulation methods-transcranial magnetic stimulation, deep brain stimulation, and electroconvulsive therapy-have been investigated in treatment-resistant patients with OCD. However, available data about the use of these techniques in OCD treatment are quite limited in terms of sample size and study design, given the difficulty in conducting standard blinded trials for these procedures. In addition, none of the mentioned treatments have received Food and Drug Administration approval for the treatment of OCD. Nevertheless, promising findings regarding efficacy, tolerability, and non-invasiveness and/or reversibility of these techniques have increased interest in investigating their use in treatment-resistant OCD.

Deep Brain Stimulation↗

PubMed2005

The impact of comorbidity on the management of pathological gambling.

A 30-year-old woman with severe pathological gambling and cyclothymia presented to our program with no previous history of pharmacologic or psychotherapeutic treatment. Pathological gambling is an impulse -control disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) in which comorbidity is common, particularly with substance abuse, obsessive-compulsive disorder and mood disorders. As described in this case, pathological gamblers with bipolar comorbidity may be effectively treated with mood stabilizers such as lithium. After receiving 10 weeks of lithium treatment, the patient showed improvement in both gambling behavior and affective instability. The identification of specific subtypes among patients with pathological gambling may be relevant to the choice of pharmacologic treatment.

Adult↗

PubMed2005

A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism.

Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebo-controlled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.9+/-4.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.

Administration, Oral↗

PubMed2005

Imaging monetary reward in pathological gamblers.

We acquired two 18F-deoxyglucose positron emisssion tomography (PET) scans on seven unmedicated pathological gamblers, at least 7 days apart. Following an injection of 5 mCi FDG, subjects carried out a computer blackjack task for 35 min under two different reward conditions: monetary reward and computer game points only. Relative FDG metabolic rate was obtained from regions of interest in the prefrontal cortex, cingulate, striatum and visual cortex. Monetary reward blackjack was associated with significantly higher relative metabolic rate in the primary visual cortex (Brodmann area 17), the cingulate gryus (Brodmann area 24), the putamen and prefrontal areas 47 and 10, compared to blackjack playing for points only. No area tested showed a significant decrease. This pattern suggests heightened limbic and sensory activation in the gambling for money condition with increased emotional valence and greater risk and reward, and confirms the salience of monetary reward in the development of pathological gambling.

Adult↗

PubMed2005

Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders?

OBJECTIVE: Selective serotonin reuptake inhibitors may be effective for some patients with pathological gambling, but those with comorbid conditions, such as bipolar spectrum disorders, may relapse during treatment. To the authors' knowledge, this is the first placebo-controlled treatment study in pathological gamblers with bipolar spectrum disorders; it compares sustained-release lithium carbonate to placebo. METHOD: Forty pathological gambling patients with bipolar spectrum disorders entered a 10-week randomized, double-blind, placebo-controlled treatment study of sustained-release lithium carbonate. Outcome measures included gambling severity, mood, anxiety, and impulsivity scales. RESULTS: Pathological gambling patients with bipolar spectrum disorders significantly improved while taking sustained-release lithium carbonate compared to placebo on total pathological gambling scores on the Yale-Brown Obsessive Compulsive Scale, including both thoughts/urges and behavior, as well as on the Clinical Global Impression severity of pathological gambling scale. Affective instability (the Clinician-Administered Rating Scale for Mania score) was also lower in the group treated with sustained-release lithium carbonate compared to placebo. Ten (83%) of 12 completers were rated as responders in the sustained-release lithium group versus five (29%) of 17 in the placebo group. Of note, improvement in gambling severity was significantly correlated with improvement in mania ratings. CONCLUSIONS: Sustained-released lithium may be an effective treatment in reducing both gambling behavior and affective instability in pathological gamblers with bipolar spectrum disorder. This study highlights the need to identify subgroups of pathological gambling patients with bipolar spectrum conditions because this may have important treatment implications.

Adult↗

PubMed2005

Impact of trait impulsivity and state aggression on divalproex versus placebo response in borderline personality disorder.

OBJECTIVE: The authors' goal was to determine whether specific pretreatment clinical characteristics differentially predict favorable treatment response to divalproex versus placebo for impulsive aggression in patients with borderline personality disorder. METHOD: Fifty-two outpatients with DSM-IV borderline personality disorder were randomly assigned to receive divalproex (N=20) or placebo (N=32), double-blind, for 12 weeks. Trait impulsivity symptoms were determined by using the Barratt Impulsiveness Scale, and state aggression symptoms were determined by using the Overt Aggression Scale modified for outpatients. Affective stability was determined by using the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Analyses were performed to identify possible baseline symptom domains that predict treatment response. RESULTS: Divalproex was superior to placebo in reducing impulsive aggression in patients with borderline personality disorder. Divalproex-treated patients responded better than placebo-treated patients among those with higher baseline trait impulsivity symptoms and state aggression symptoms. The effects of baseline trait impulsivity and state aggression appear to be independent of one another. However, baseline affective instability did not influence differential treatment response. CONCLUSIONS: Both pretreatment trait impulsivity symptoms and state aggression symptoms predict a favorable response to divalproex relative to placebo for impulsive aggression in patients with borderline personality disorder.

Adult↗

PubMed2005

Neurological soft signs as predictors of treatment response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder.

Neurological soft-sign abnormalities have been implicated in obsessive-compulsive disorder (OCD). This first comprehensive data analysis evaluated the association between baseline neurological soft signs and treatment response in 117 OCD patients treated with controlled-release fluvoxamine in a double-blind placebo-controlled trial. Total and right-sided soft signs for the responders and the nonresponders did not differ significantly. Left-sided visuospatial soft signs were significantly increased in treatment nonresponders compared to responders. These subtle neurological abnormalities may implicate a potential subgroup of OCD patients with poorer treatment response. This may have treatment implications and therefore serve as a screening tool in OCD.

Double-Blind Method↗

PubMed2005

Fluvoxamine: a selective serotonin re-uptake inhibitor for the treatment of obsessive-compulsive disorder.

Fluvoxamine is the selective serotonin re-uptake inhibitor with the largest database in the treatment of obsessive-compulsive disorder, a severe, and often chronic, anxiety disorder associated with substantial impairment in functioning. The selective serotonin re-uptake inhibitors represent a first-line treatment in patients with obsessive-compulsive disorder. These agents work primarily by blocking the re-uptake of serotonin into the presynaptic nerve terminal, which is believed to be mediated by their effects on the serotonin transport system. In the last two decades, the anti-obsessional effect of fluvoxamine has been tested in several double-blind, placebo-controlled and active-comparison studies, demonstrating its superior efficacy over obsessions and compulsions compared with non-serotonergic antidepressants (i.e., desipramine) and equal efficacy to clomipramine (a tricyclic antidepressant with potent serotonin re-uptake inhibition) and other selective serotonin re-uptake inhibitors (paroxetine and citalopram). However, compared with clomipramine, the selective serotonin re-uptake inhibitor fluvoxamine showed fewer side effects and better tolerability. This reflects the poor affinity of this compound for adrenergic, muscarinic, cholinergic or histaminergic receptors.

Fluvoxamine↗

PubMed2005

Dissociation and posttraumatic stress 1 year after the World Trade Center disaster: follow-up of a longitudinal survey.

BACKGROUND: We conducted a 1-year follow-up of an original mail survey of early reactions to the World Trade Center disaster. METHOD: Of the 75 subjects originally surveyed, 58 (77%) responded. The survey included measures of dissociation (Dissociative Experiences Scale, Cambridge Depersonalization Scale, Clinician-Administered Dissociative States Scale), post-traumatic stress (Impact of Event Scale-Revised), social support (Interpersonal Support Evaluation List-short form), and a life quality measure (Quality of Life Enjoyment and Satisfaction Questionnaire-short form). We hypothesized that dissociative versus posttraumatic symptoms at follow-up could be dissected on the basis of early reactions. RESULTS: Responders and nonresponders did not differ in baseline characteristics. Exposure was not associated with dissociation or posttraumatic stress at follow-up. Of distress, dissociation, and posttraumatic stress at baseline, baseline dissociation was the strongest predictor of outcome dissociation while baseline posttraumatic stress was the strongest predictor of outcome posttraumatic stress. Of 4 peritraumatic distress factors generated in the original survey, "loss of control" and "guilt/shame" were significantly related to dissociation and posttraumatic stress at outcome, while "helplessness/anger" was only associated with posttraumatic stress at outcome. Lesser improvement in posttraumatic stress over the first year was significantly related to less social support and greater comorbid dissociation. Interim social support was associated with better life quality and fewer symptoms at outcome. CONCLUSION: There was evidence for partly independent pathways toward dissociation versus posttraumatic stress 1 year after the disaster. Feelings of guilt and shame, and persistent dissociation, were poor prognostic factors, while social support had a powerful ameliorating influence.

Adult↗