Adverse Effects of Fluoxetine

LEITERS TO THE EDITOR havior were more co nsistent than those seen with meth ylphen idate , which differs from placeb o only at marginal levels (p = 0.056) at this stage of the study . As in other studi es, fenflu ramine caused drowsiness in some children (although not seve re in any case), and the differences appro ached significance both in comparison with placebo (p = 0.052 ) and methylphenidate (p = 0.052) . We observed a nonsignificant trend for fenfluramine to cause anorexia, but so far, this is less apparent than the differences between methylphen idate and placebo (p < 0.10). We have also a seen a nonsignific ant tenden cy for less akathisia with fenfluram ine than with placebo (p = 0 .068) , which may be as a result of a mild anx iolytic effect or may be secondary to the reduction in activity level. One hereto fore unreported side effect is a very vivid report of a 7-year-old girl who developed a peculi ar body odor and halitosis that coincided exactly with the times of fenfluramine treatment. We observed no increa ses in insomnia , dizziness , or diarrhea with fenflur amine, although these are sometimes reported to occur with the drug (Aman and Kern , 1989). We also looked at heart rate, blood pressure , and body weight in these children. Analysis of varian ce indic ated that all three cardiovascular measures were significantly affected by the medications. Fenfluramine was associ ated with reductions in each , but all significant comparisons were with respect to meth ylphenidate , which tended to eleva te heart rate and blood pressure. As in most studies, fenfluramin e produced significant weight losses in these children (p = 0 .01 ). Our subjects lost about 1.8 pound s (0 .82 kg) relative to their placebo weights during the 4 weeks they received medication. Finally, two groups of symptom s that do not appear on the DOTES Scale occurred fairly often in our sampl e. Seven of our subj ects were reported to have difficulties with enure sis and encopresis, and another four demon strated stereotypy and self-injurious behavior. Enure sis and encopresis were lowest when the children were taking methylphenidate, appe aring to worse n both with placebo (p = 0. 068) and fenfluramin e (p = 0.068) . Th e emer gence of these symptoms (usually in children who had previou sly been maintained on methylphenidate) has probably caused more distress than any other side effect in this study . Furthermore , it is a well-est ablished fact that moderate-to-high doses of psychostimul ants can induce stereotypic behavior in laboratory animal s (Randrup and Munk vad, 1974 ), and stero typies may occur de novo (or existing stereotypies may be exacerbat ed) at lower doses of stimulants in children with developmental disabilities (Aman, 1982). Both enure sis/encopresis and stere otypy /self-injur y are obviously of relevance to researcher s and clinicians working with developmentally delayed clinical populations. Other research ers working with development ally delayed children may wish to add these symptoms to their inventory of side effects if they are using the DOTES to monitor side effec ts. Furthe rmore , if the DOTES is revised in the future , its developers should seriously consider addin g these and other relevant items to document such potenti al side effects. Michael G. Aman , Ph.D. Richard A . Kern , M.D . L. Eugene Arnold, M .D . Debbie E. McGhee , B.A . The Nisonger Cent er for Ment al Retardati on and Developmental Disabil ities Ohio State University , Columbus, Ohio REFER ENCES

Aman, M. G. (1982) , Stimul ant drug effects in developmental disorders and hyper activit y-toward a resolution of disparate findings. J . Autism Dev, Disord. , 12:385-398. Aman, M . G . & Kern , R. A. (1989) , Review of fenfluramine in the treatment of the devel opmental disabilitie s. J. Am . A cad . Child Adolesc. Psychiat ry , 28 :549-565 . Donnell y , M., Rapoport , J . L. , Potter , W. Z., Oliver , J . , Keysor ,

508

C. S . & Murphy, D. L. (1989), Fenfluramine and dextroamphetamine treatment of childhood hyperactivit y . Arch . Gen . Psychiatry , 46:205-21 2. Guy, W . (1976) , ECDEU Assessm ent Manual f or Psychoph armacology, (Rev . Ed.). Rockville , MD : U.S. Department of Health , Education , and Welfare. Randrup , A. & Munkvad , 1. (1974) , Pharm acology and physiolog y of stereotyped behavior. J , Psychiat r . Res. , 11:1-10 . Rapoport , J. L. & Conner s, C . K. (eds .) (1985 ), Special feature: rating scales and assessment instrum ents for use in pediatric psychopharmacology research . Psychoph armacol . Bull ., 21:7 19-1125.

Adverse Effects of Fluoxetine To the Editor: Increased anxiety and stereo typical beha viors in response to changing fluoxetine dosage from 20 mg every other day after 2 weeks to 20 mg every day in a 26-year-old white autistic female (Mehlinger et aI., 1990) may have been due to the serotonergic-mediated inhibition of dopamine lateraliz ed to the right hemisphere of the brain in which the metabolic rate is higher in femal es (Friedman and Janko vic, 1990). This hypothesis is supported by the stereotyped, rituali stic behaviors in autisti c individual s resemblin g compul sive behavi or (Mehlinger et aI., 1990) linked to right frontal brain dysfunction (Friedman and Jankovic, 1990). Adver se respon ses to fluoxetine may be the result of a sudden increa se in serotonin that might be avoided by a more gradual dose titration (Papp et aI., 1990). Ernest H . Friedman , M.D. East Cleveland, Ohio REFERENCES

Friedman, E. H. & Jankovic, J. (1990), Tardi ve oculogyria (letter and reply). Neurology , 40 :728. Mehling er , R. , Scheftner, W . A. & Poznanski , E. (1990) , Fluoxetine and autism (letter ). J . Am . Ac ad . ChildAdolesc. Psychiatry, 29:985. Papp , L. A. , Gorman , J. M. , Teicher , M . H . , Glod , C. & Cole, J . O. (1990), Suicidal preoccup ation durin g fluoxetine treatment (letter and reply). Am . J . Psychiatry , 147:1380--1381 .

Fluoxetine in Autism with Depression To the Editor: We enjo yed reading the report on the use of fluoxetine in autism by Mehlin ger et al. (1990). We agree that fluoxetine may be useful in the treatment of persons with autism . Our expe rience with this drug has been simila r to that of Mehlinger et al. with some exceptions as described below: Case 1 J. F. , a 16-year-old girl with autism and moderate mental reta rdation, was referred with a 3-week histor y of chan ge of behav ior that consisted of social withdrawal, povert y of speech, a general lack of interest in hobbie s, and disturbance of sleep and of appetite. Her other behaviors consisted of lining up objects and compulsively carrying obje cts with her. There was a strong famil y history of affective disorder. After a careful assessment, a diagnosis of major depre ssion in addition to her developmental disorder s was made , and treatment with fluoxet ine, 20 mg/d , was started . About 2 weeks after starting the medic ation , her parents reported that the patient was much better . She looked brighter, and her vege tative features also improved. Howe ver, there was no decrease in her compulsive behaviors . In view of the respon se, fluoxetine was increased to 20 mg twice a day . Two week s later , her parents reported l .Am . A cad. Child Ado/esc. Psychiatry, 30:3, May 1991