ABSTRACT
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by clinically significant anxiety, but few empirical data guide treatment of children meeting full DSM-IV criteria for ADHD and anxiety disorders (ADHD/ANX). This study examined the efficacy of sequential pharmacotherapy for ADHD/ANX children. METHOD: Children, age 6 to 17 years, with ADHD/ANX were titrated to optimal methylphenidate dose and assessed along with children who entered the study on a previously optimized stimulant. Children with improved ADHD who remained anxious were randomly assigned to 8 weeks of double-blind stimulant + fluvoxamine (STIM/FLV) or stimulant + placebo (STIM/PL). Primary efficacy measures were the Swanson, Nolan, Atkins, and Pelham IV Parent and Teacher Rating Scale ADHD score and the Pediatric Anxiety Rating Scale total score. ADHD, ANX, and overall Clinical Global Impressions-Improvement scores were also obtained. RESULTS: Of the 32 medication-naive children openly treated with methylphenidate, 26 (81%) improved as to ADHD. Twenty-five children entered the randomized trial. Intent-to-treat analysis indicated no differences between the STIM/FLV (n = 15) and STIM/PL groups on the Pediatric Anxiety Rating Scale or Clinical Global Impressions-Improvement-defined responder rate. Medications in both arms were well tolerated. CONCLUSIONS: Children with ADHD/ANX have a response rate to stimulants for ADHD that is comparable with that of children with general ADHD. The benefit of adding FLV to stimulants for ANX remains unproven.
Subject(s)
Anxiety Disorders/drug therapy , Anxiety Disorders/epidemiology , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/epidemiology , Central Nervous System Stimulants/therapeutic use , Fluvoxamine/therapeutic use , Methylphenidate/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adolescent , Anxiety Disorders/diagnosis , Attention Deficit Disorder with Hyperactivity/diagnosis , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/adverse effects , Child , Comorbidity , Dose-Response Relationship, Drug , Double-Blind Method , Female , Fluvoxamine/administration & dosage , Fluvoxamine/adverse effects , Humans , Male , Methylphenidate/administration & dosage , Methylphenidate/adverse effects , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/adverse effectsABSTRACT
A versatile route for the synthesis of homochiral alpha-ketoamide analogues of amino acids is described. Incorporation of this functionality into peptide sequences using either solution or solid-phase chemistry resulted in potent inhibitors of the Hepatitis C Virus NS3 proteinase.