Source: Riddle MA, Bernstein GA, et al. Anxiolytics, adrenergic agents, and naltrexone. J Am Acad Child Adolesc Psychiatry. 1999;38(5):546–556.Riddle and colleagues systematically reviewed the efficacy and safety of 3 classes of medications used to treat various psychopathologies in children and adolescents: anxiolytic medications (including benzodiazepines, buspirone, and other serotonin 1A agonists), adrenergic agents (beta-blockers and the alpha 2-adrenergic agonists clonidine and guanfacine), and the opiate antagonist naltrexone. All available controlled trials and selected uncontrolled studies of these medications in children and adolescents published in English through 1997 were reviewed. Other classes of drugs used as anxiolytics, eg, tricyclic antidepressants1 and selective serotonin reuptake inhibitors,2 are reviewed in other articles in this journal issue.The authors found virtually no controlled data to support the efficacy of most of these drugs in the treatment of psychiatric disorders in children and adolescents. For some drugs, eg, buspirone and guanfacine, no controlled studies have been carried out in children and/or adolescents. For other drugs, eg, clonidine and naltrexone, most placebo-controlled studies have failed to demonstrate efficacy.Clonidine has been used since the late 1970s for children with Tourette’s and other tic disorders. In 4 of 5 placebo-controlled studies of treatment of Tourette’s disorder, clonidine was no more effective than placebo in reducing the severity of tic symptoms. Later, clonidine became an alternative to stimulants for children with attention deficit hyperactivity disorder (ADHD) alone or comorbid with Tourette’s disorder. Selection criteria of the ADHD subjects in these studies limits the generalizability of the findings. In 3 of 5 controlled studies of the efficacy of clonidine for the treatment of Tourette’s disorder in children with ADHD symptoms, the effects of clonidine on symptoms of ADHD were not significant. There have been no controlled studies to support the combined use of clonidine and methylphenidate for ADHD.The authors note that the lack of evidence from controlled trials of clonidine for the treatment of tics and ADHD suggests that “additional controlled trials may not be needed for these medications.” They strongly recommend controlled studies in children and adolescents for benzodiazepines for acute anxiety; buspirone (and newer serotonin 1A agonists) 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.An important finding of the Riddle et al article is that most of the controlled studies of clonidine have failed to support efficacy in the treatment of either ADHD or Tourette’s disorder and that there are no controlled studies supporting the combined use of clonidine and methylphenidate for ADHD. The use of clonidine to treat ADHD has increased dramatically with approximately 150,000 to 200,000 prescriptions written per year in 1995. An estimated 61,000 prescriptions were written for the combination of methylphenidate and clonidine. This increase of use, the lack of controlled studies supporting efficacy, and concerns about the safety of this combination (4 cases of death in children taking this combination) prompted the editors of the Journal to publish (pages 614–622 in the same issue) a thoughtful debate by experts in the field concerning the use of clonidine with methylphenidate. That discussion is worthwhile reading.This review is one of series of reviews on the safety and efficacy of medications used to treat developmental, behavioral, and psychiatric disorders in children and adolescents published in a special section of this issue of the Journal of the American Academy of Child & Adolescent Psychiatry. These articles point out the critical gaps in our current knowledge about these agents and the urgent need for well-controlled studies on safety and efficacy.We believe this is an extremely important article that should give us all pause. Most behavior problems in children and adolescents are first brought to the attention of the pediatrician, who must make a diagnosis and decide on a course of action. Because few of us have extensive experience with many of the medications used to treat psychiatric disorders, we often turn to experts for consultation. This article points out that many of the drugs our colleagues recommend have not been adequately investigated for use in children, either for efficacy or for safety. Some drugs, such as clonidine as used in ADHD, have actually been shown NOT to be effective but are still widely recommended. This article reminds us of the need to base our care on evidence when it is available, and to press our consultants to search for and supply us with information on efficacy and safety to accompany their recommendations. At a minimum, when such information is not available we and our patients’ parents should be informed that there is little data to support the use of such medications in children.