CLINICAL PERSPECTIVESAssistant Editors: Michael S. [ellinek, M.D.

Joseph Biederman, MD.

Clonidine for Posttraumatic Stress Disorder inPreschool Children

ROBERT J. HARMON, M.D., AND PAULA D. RIGGS, M.D.

Posttraumatic stress disorder (PTSD) in severelyand chroni­cally abused and neglected preschool children often resultsin extreme and disabling symptoms that cannot be managedoutside of a highly structured program, e.g., in a psychiatricday hospital. Even when the milieu treatment is supple­mented with individual, group, behavioral management , andfamily therapies, some children remain difficult to manage,both in the therapeutic program and at home, without theuse of psychotropic medication. Although one hesitates touse medication with this age group, the severity of thesymptoms and the difficulties in managing the behaviorof these children, even during psychiatric day treatment,necessitated our considering that the benefits of such treat­ment might outweigh the risks associated with psychophar­macological intervention.

Given the recent suggestion that c1onidine, a presynaptic<x2-adrenergic agonist, is useful in the treatment of adultPTSD (Friedman, 1988; Rosenberg et al., 1994) and thatsome clinicians are also using it to treat childhood PTSD(Marmar et al., 1993), we initiated a limited open clinicaltrial using clonidine with the 3- to 6-year-old preschoolchildren entering our program. We considered clonidineonly in those children who met DSM-IV criteria for PTSD(American Psychiatric Association, 1994), when their PTSDsymptoms of hyperarousal, impulsivity, and aggression re­mained severe and had not abated with individual, family,and structural/behavioral treatment approaches after at least1 month in treatment.

Accepted December 29, 1996.From the Department of Psychiatry, University of Colorado School of

Medicine, Denver. Dr. Harmon is Professor and Head, Division of Child

Psychiatry, and Director ofInfant Psychiatryand the Kempe Center TherapeuticPreschool. Dr. Riggs is Assistant Professor and Director ofPsychiatric Services

for Adolescents in the Addiction Research and Treatment Services Program.This research was supported, in part, by NIDA grant DA06941. The

authors thank Randy Rossfor his feedback on the paper and Nancy Murrow. for the literature searches and editing.

Reprint requeststo Dr. Harmon. UCHSC Box C268-52. 4200 East NinthAvenue. Den ver. CO 80262.

0890-8567/96/3509-I247$03.00/0 ©I996 by the American Academyof Child and Adolescenr Psychiatry.

We report our clinical experience using clonidine in seven 'preschool children whose ages ranged from 3 to 6 years.All of the children were referred to the day hospital fortreatment of symptoms related to severe physical and/orsexual abuse and neglect. Upon admission, these childrenreceiveda thorough psychiatric evaluation by a child psychia­trist and met DSM-IV diagnostic criteria for PTSD . Somechildren had additional comorbid depressive features, atten­tional problems, and reactiveattachment disorder. Clonidinewas used to target persistent and distressing symptoms ofinitial insomnia as well as other sleep difficulties (e.g.,nightmares), hyperarousal, hypervigilance, impulsivity, gen­eralized anxiety, mood lability, oppositionality, and aggres­sion-all predominantly characterized clinically under therubric of PTSD.

The therapeutic milieu of the preschool/day hospital iswell established and includes a 4-hour day treatment periodwith highly structured therapeutic and educational activities.These activities include twice-weekly individual psychother­apy, twice-monthly family/parental therapy, pediatric screen­ing and management , and regular case management. Mostof the children remain in the program for 2 years. Manychildren continue their attendance in the therapeutic dayhospital after entering kindergarten, spending half a day ineach setting (program described in Oates et al., 1995).Almost all of the children entering this program are fromlower socioeconomic backgrounds and the majority haveresided in foster or adoptive families. Approximately equalnumbers of males and females enter the program, withthe ethnic distribution being approximately 50% African­American, 25% Hispanic, and 25% Caucasian.

All of the children considered for a trial of clonidine werephysicallyhealthy and free from known cardiac, neurological,or other major medical illness. They received a physicalexamination by a pediatrician, and all of them had normalbaseline pulse and blood pressure prior to starting c1onidine.We were able to obtain baseline electrocardiograms (ECGs)on three of the seven children, which were normal prior tostarring clonidine. Two of the children with baseline ECGswere also being treated with imipramine for depressive

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HARMON AND RIGGS

symptoms; the other children were not taking any otherpsychotropic medications during their treatment withclonidine.

Children were only considered for a trial of clonidine ifafter at least 1 month, but often after several months intreatment, their severe symptoms of PTSD had not beenalleviated significantly with a combination of individual,milieu, family, and behavioral interventions (with the excep­tion of one boy with severe PTSD who was already beingtreated with clonidine at the time of admission to thepreschool). Specific target symptoms (mentioned previously)were identified for each child prior to the initiation ofclonidine treatment. Once these criteria were met and afterobtaining informed consent from parenrtsl/guardiants), mostchildren were given an oral dose of0.05 mg ofclonidine. Thisgenerally occurred on a Monday morning at the preschool sothat the children could be carefully observed and monitoredfor adverse side effects while starting the medication. If thisinitial dose was tolerated; an additional 0.05 mg of clonidinewas given at bedtime. Most children experienced moderatesedation for the first week while taking the oral dose ofclonidine, but it was generally transient. After stabilizationand resolution of the sedation, the average maintenance doseof clonidine ranged from 0.1 mg at bedtime only (in twoof seven children, in whom clonidine was used primarilyto manage sleep difficulties) to the highest dose of 0.05 mgb.i.d. and 0.1 mg at bedtime (in one of the seven children).The average decline in either diastolic or systolic bloodpressure from baseline levels was less than 10%. No childcomplained of dizziness, which would have been an indica­tion for orthostatic blood pressure assessment. Six of theseven children began with oral clonidine versus a clonidinepatch. Within this group, four of the six children complainedof or were observed to have initial sedation as a result ofthe clonidine. No other side effects of oral clonidine werenoted (e.g., agitation, delirium, dizziness, dry mouth, nauseaor vomiting, or constipation).

In an effort to avoid the initial sedating effects of oralclonidine and the inconvenience of a daily oral medication,we began using the clonidine patch (Catapres-T'I'S'P). re­placed every 5 days. We found that the patch was toleratedbetter than the oral clonidine, with less initial sedation (evenin the child who had started with the patch instead of theoral preparation). Using the clonidine patch resulted ingreater compliance with treatment and appeared to be equallyeffectivein controlling target symptoms. Patches were usuallyreplaced at the school. For children with oily skin, the patchlocation (usually the upper back area) was cleaned withalcohol prior to placement. Despite our initial concernsabout patches not remaining on a child's back for consistentmedication delivery, we found that this was not much ofa problem. The following adverse side effects were associated

with the patch: (1) in two of seven children, mild localirritation and erythema developed under the patch, but thiswas transient and was managed by moving the patch todifferent locations and using hydrocortisone cream; (2) oneboy consistently pulled the patch off ofhis back, necessitatinga switch back to oral clonidine; and (3) one boy developeda severepoststreptococcal glomerulonephritis with hyperten­sion during treatment with clonidine. The boy's parentshad abruptly discontinued the clonidine patch prior tohospitalization for his renal problems. His blood pressurewas 150/100 upon admission to the hospital. The admittingphysician thought that the abrupt discontinuation of cloni­dine may have contributed to the boy's hypertension as hadhis renal impairment from the glomerulonephritis.

The target symptoms (listed below) were assessed on aweekly basis after initiation of and throughout medicationtreatment. However, the efficacy of the therapeutic effectwas noted after the sedating effects of the medication hadabated, dosage had been stabilized, and route of administra­tion had been established (usually 3 to 4 weeks later). Targetsymptoms of PTSD that were rated as moderately to greatlyimproved with clonidine treatment by both the teachers andphysician(s) were as follows: aggression (all seven children),impulsivity (five of seven), emotional outbursts and moodlability (fiveofseven), hyperarousal (fiveofseven), hypervigi­lance (five of seven), generalized anxiety (five of seven),oppositionality (fiveof seven), and insomnia and nightmares(five of seven). In addition, peer and staff relationshipsimproved for all seven children during treatment with cloni­dine. One boy also had a marked decrease in repetitivetraumatic play during clonidine therapy, and a girl had adecrease in dissociative episodes after stabilization of cloni­dine therapy.

In summary, these preliminary clinical data seem to indi­cate clonidine's effectiveness in reducing symptoms ofaggres­sion, hyperarousal, and sleep difficulties in children withsevere PTSD. Many parents felt that the medication wasthe most significant aspect of their child's treatment, resultingin the greatest improvement in target symptoms and behav­ior. Both staff and parents noted that the medication wasoften necessary to enable the child to take advantage ofother treatment modalities.

We emphasize that the use of psychotropic medicationsin preschool children, as with children in general, must beapproached with caution and only after a thorough psychiat­ric evaluation with broad diagnostic assessment. p'urther­more, psychopharmacological intervention should beconsidered only after psychological, behavioral, and familyinterventions or treatments have been implemented andjudged to have not adequately ameliorated the symptoms.In addition, target symptoms must be clearly characterizedand followed.

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Since we conducted this clinical trial, there have beenrecent concerns regarding the use of clonidine in the treat­ment of children (Chandran, 1994; Walkup, 1995). In lightof these concerns, particularly related to ECG changes inchildren, and our own clinical experience, we offer thefollowing recommendations for those using clonidine in thetreatment of severe PTSD in preschool-age children: (1)acquire informed consent and carefully consider parental!guardian compliance since precipitous discontinuation ofclonidine can be dangerous; (2) use only in children freefrom cardiac or other major medical illness; (3) obtainbaseline pulse, blood pressure, and ECG; (4) follow targetsymptoms closely; (5) use the lowest clinically effectivedose; (6) obtain postclonidine pulse and blood pressure andconsider follow-up ECG; and (7) seek a dose or route ofadministration that minimizes sedation.

Although these preliminary data are promising, this opentrial is limited by the lack of controls and standardizedassessments and the small number of subjects. A larger,

CLINICAL PERSPECTIVES

placebo-controlled trial is indicated to determine the efficacyand safety of clonidine for severe PTSD symptoms in pre­school children.

REFERENCESAmerican Psychiatric Association (1994), Diagnostic and Statistical Manual

ofMentalDisorders, 4th edition (DSM-IV). Washington, DC: AmericanPsychiatric Association

Chandran KSK (1994), ECG and clonidine (letter). JAm Acad ChildAdolesc Psychiatry 33:1351-1352

Friedman M] (1988), Toward rational pharmacotherapy for posttraumaticstress disorder: an interim report. Am J Psychiatry 145:281-285

Marmar CR, Foy 0, Kagan B, Pynoos RS (1993), An integrated approachfor treating posttraumatic stress. In: Posttraumatic Stress Disorder: AClinical Review, Pynoos RS, ed. Lutherville, MD: Sidran Press, pp99-132

Oates RK, Gray], Schweitzer L, Kempe RS (1995), A therapeutic preschoolfor abused children: the KEEPSAFE project. Child Abuse Negl19:1379-1386

Rosenberg DR, Holtrum ], Gershon S (1994), Textbook ofPharmacotherapyfor ChildandAdolescent Psychiatric Disorders. New York: Brunner/Maze!

Walkup ]T (1995), Methylphenidate and clonidine. MCAP News26:11-12

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