LETTERS TO THE EDITOR
mother agreed he would normally have shaken off without difficulty. Although he had some history of "taking things hard," including tearfulness, the degree of upset at this time was different. He did not appear otherwise depressed, nor did he acknowledge depressed or irritable feelings. He noted that the wish to die persisted: "I couldn't put it out of my mind." He was distressed at not knowing what to do about this feeling. In the meantime, he noted a decrease in feeling that he had to read sentences over and over. Clomipramine was reduced to 25 mg/day without recurrence of the suicidal ideation during 4 months of follow-up and with complete relief from obsessive and compulsive symptoms. The seriousness of the symptom and its relevance to the possible induction of self-destructive ideation or behavior by fluoxetine make this report of interest. Although fluoxetine and clomipramine are not structurally related, they both increase serotonin activity through blocking reuptake. The possible mechanisms of acute suicidality have been recently debated by King et al. (l99Ia, b) and by Fuller and Beasley (1991). This appears to be the first report of new suicidality in a patient taking clomipramine.
among autistic subjects (Gillberg and Steffenburg, 1987) and of psychosis among epileptics (McKenna et aI., 1985), but an association of the two in monozygotic twins is rare. There has been much discussion of the relations between autism and epilepsy, which seem on the latest evidence to be the outcome of a common cerebral dysfunction (Olsson et aI., 1988). Our cases evidence the concordance in the twins of two pathological conditions (autism and epilepsy), probably of heterogeneous genetic origin with different involvement of genetic and nongenetic factors in the two patients. In both subjects, there was interaction between hereditary factors (family history of psychiatric illness) and homogeneous acquired factors (pre- and perinatal distress). Our report confirms the data of Vukicevic and Siegel (1990) on the primary importance of suboptimal factors in the fetal or neonatal periods to normal neuropsychic development. Similar remarks apply to the multifactorial pathogenesis of epilepsy, for it has recently been recognized that genetic factors are involved even in partial epilepsy (Ottman et aI., 1989). One last point regarding the EEG abnormalities recorded from the left temporal lobe: a left temporal EEG focus is considered to be most frequently associated with psychosis in adults (Perez et aI., 1985).
Gordon Harper, M.D. The Children's Hospital Boston, Massachusetts
Prof. Carlo Lenti Universita Degli Studi Di Milano Milan, Italy
REFERENCES
REFERENCES
Fuller, R. F. & Beasley, C. M., Jr. (1991), Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849 (letter). King, R. A., Riddle, M. A., Chappell, P. B., Hardin, M. T., Anderson, G. M., Lombroso, P. & Scahill, Z. (199Ia), Emergence of selfdestructive phenomena in children and adolescents during fluoxetine treatment. J. Am. Acad. Child Adolesc. Psychiatry, 30: 179-186. - - Anderson, G. M., Rasmusson, A. & Riddle, M. A. (l99Ib), Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849-850 (letter).
Gillberg, C. & Steffenburg, S. (1987), Outcome and prognostic factors in infantile autism and similar conditions. J. Autism Dev. Disord., 17:271-275. McKenna, P. J., Kanej, M. & Parrish, K. (1985), Psychotic syndromes in epilepsy. Am. J. Psychiatry, 142:895-904. Olsson, I., Steffenburg, S. & Gillberg, C. (1988), Epilepsy in autism and autistic-like conditions: a population-based study. Arch. Neural., 45:666-668. Ottman, R., Annegers, J. E., Hauser, W. A. & Kurland, L. T. (1989), Seizure risk in offspring of parents with generalized versus partial epilepsy. Epilepsia, 30:157-161. Perez, M. M., Trimble, M. R., Murray, N. M. F. & Reider, I. (1985), Epileptic psychosis: an evaluation of PSE profiles. Br. J. Psychiatry, 146:155-163. Vukicevic, J., Siegel, B. (1990), Pervasive developmental disorder in monozygotic twins. J. Am. Acad. Child Adolesc. Psychiatry, 29:897-900.
Autism and Epilepsy: Organic Connections? To the Editor: We read with interest the report of Vukicevic and Siegel (1990) on pervasive developmental disorders in monozygotic twins. We report a similar case of autism and epilepsy in male monozygotic twins. Case report: An aunt of the twins' mother suffers from chronic psychosis and is hospitalized in a psychiatric institution. A brother of the father has a primary affective disorder. There was probable fetal damage, as a result of a threatened miscarriage at the 36th week and complete detachment of the placenta at the 39th week, and definite neonatal distress. Born by cesarean section, the first twin presented an Apgar score of 7 at I minute and 9 at 5 minutes; the second twin had a score of 3 at I minute and 5 at 5 minutes. Psychomotor development was delayed in both boys, and they did not learn to walk until 2 years of age. They never learned to speak, and frorv the first years of life, they displayed the characteristic symptoms of autism: lack of social interaction and ability to play, stereotyped behaviors, and so on. The first twin began to have complex partial seizures at age II, and these recurred monthly. The second twin had a similar seizure 8 months later, with a single recurrence after 6 months. Kariotyping with search for fragile X, magnetic resonance imaging, and tests for abnormalities ofthe sugar, amino acid, and mucopolysaccharide metabolism revealed nothing abnormal. Only a CT brain scan revealed signs of atrophy in both twins. EEG showed spike activity over the temporal and central regions of the left hemisphere, more evident in the second twin. Numerous studies have demonstrated a high frequency of epilepsy
370
Biological Liability in Families with Autism To the Editor: Piven et al. (1990, 1991) have provided a well-designed comprehensive study of psychiatric disorders in adult siblings and parents of autistic probands. Our family history studies support their findings, extending the findings to second-degree relatives, which strengthens one hypothesis that some of the psychiatric symptomatology may be an expression of underlying biological liability in families with autism. One study was designed using the mother of the autistic probands as the main informant for autistic probands, siblings, and seconddegree family members, i.e., grandparents, aunts and uncles, nieces and nephews. Family history was obtained using a family history questionnaire that included questions pertaining to medical and psychiatric illness, medication usage, and learning disabilities. When a sibling or other family member was identified, diagnosed, or treated for psychiatric illness, a first-person structured psychiatric interview, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) was conducted (Spitzer and Endicott, 1978). Diagnoses were made using research diagnostic criteria (Spitzer and Robins, 1978). When family members were deceased or unavailable, a secondJ. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992
LETTERS TO THE EDITOR
hand SADS-L structured interview with the mother as informant was completed. Learning disabilities were included when they were diagnosed within the school system and/or by a psychologist. The study included 13 probands (9 white, 4 black; average age, 17.8 ± 9.1 years), 26 first-degree relatives (average age of parents, 44.5 ± 12.1 years, siblings 23.3 ± 13.4 years), and 35 second-degree relatives. The probands had a relatively high rate of using psychoactive medications, 62.5%, at some time during their lives. Psychoactive medication had been prescribed for 33.3% of first-degree relatives and 26.1 % of second-degree relatives. The level of illicit drug abuse, 16% in first-degree relatives and 11 % in second-degree relatives parallels the overall rate of 16% in South Carolina, documented by the South Carolina Commission on Alcohol and Drug Abuse (SCADA). The alcohol abuse rate appears to be high, 38.1 %, in first-degree male and 37.5% in second-degree male relatives. The SCADA rate for male binge drinking on five or more occasions is 17% and for serious problem drinking is 13% in the Southeast. Learning disabilities were diagnosed based on identification within the school system. They were present in 14.3% of first-degree relatives and 12.1 % of second-degree relatives. About a third (34.8%) offirst-degree relatives and 24.2% of seconddegree relatives were classified as having "nerve problems." This closely parallels the 33% rate of psychotropic medication usage in first-degree relatives and 26.1 % in second-degree relatives. In addition, 8% of first-degree relatives and 12% of second-degree relatives had at least one psychiatric hospitalization. In our study, 10.5% of first-degree relatives and 15.6% of seconddegree relatives were diagnosed with anxiety disorder. Only 5% of first-degree relatives and no second-degree relatives had ever had a panic attack, and none were diagnosed with panic disorder. No phobic disorders were diagnosed. Panic and anxiety disorders were diagnosed less frequently in our population than in that of Piven et al. (1990, 1991). Finally, 33.3% of autistic probands, 18.2% of first-degree relatives, and 28.1% of second-degree relatives had been treated for affective disorder. No diagnosis of manic depressive disorder was present. The figures for affective disorder agree with those of Piven et al. (1990, 1991). The number of second-degree family members diagnosed with affective disorders and alcohol problems is higher than would be expected in the general population and similar to that of first-degree family members, i.e., father, mother, and siblings. These findings of a familial aggregation of affective disorder, anxiety disorders, and alcohol problems in both first- and second-degree relatives strengthen and underscore the findings of Piven et al. that these disorders are not entirely the result of raising a handicapped person (Piven et aI., 1990, 1991). Ruth K. Abramson, Ph.D. Harry H. Wright, M.D. Michael L. Cuccaro, Ph.D. Leesa G. Lawrence, M.D. Sheri Babb, M.S. Debbie Pencarinha, M.S. Frederick Marsteller, Ph.D. Elisabeth C. Harris, B.S. University of South Carolina, Columbia REFERENCES
Piven, J., Gayle, J., Chase, G. A., Fink, B., Landa, R., Wzorek, M. & Folstein, S. (1990), A family history study of the adult siblings of autistic individuals. I. Am. Acad. Child Adolesc. Psychiatry, 29:177-184. - - Chase, G. A., Landa, R., Wzorek, M., Gayle, J., Cloud, D. &
I. Am. Acad. Chi/dAdolesc. Psychiatry, 31:2, March 1992
Folstein, S. (1991), Psychiatric disorders in the parents of autistic individuals. I. Am. Acad. Child Adolesc. Psychiatry, 30:471--478. Spitzer, R. L. & Endicott, J. (1978), Schedule for affective disorders and schizophrenia, Ed. 3 (NIMH Clinical Research Branch, Collaborative Program on the Psychology of Depression). Washington, DC: U.S. Government Printing Office. - - & Robins, E. (1978), Research diagnostic criteria. Arch. Gen. Psychiatry, 35:773-82.
A Trigger for Tourette's Syndrome To the Editor: We report the apparent exacerbation of Tourette symptoms by amantadine (Symmetrel®), the antiviral agent prescribed by family practitioners for influenza-like illnesses. The motor and vocal tics as well as the attentional problems of a 9-year-old boy with Tourette's syndrome (TS) whom we had been treating for about 1 year, worsened markedly for 6 weeks after his family practitioner prescribed liquid amantadine (50 mg., three times a day) for him. TS consists of multiple motor and one or more vocal tics that vary with presentation and wax and wane with a duration of at least a year (American Psychiatric Association, 1987). The median age of onset is 7 years, with the great majority of patients experiencing the onset before age 14 years. Males (3:1) are more likely to develop the disorder than females. The onset in our patient was at 7 years of age. His presenting symptoms included neck and shoulder jerking, sniffing, throat clearing, impulsivity, inattention, and hyperactivity. He was diagnosed as having TS by a neurologist shortly after the tics began at age 7 and was treated then with diazepam (1 mg., orally, twice a day) for just over a year. On presentation to our clinic, we decided to taper and discontinue the diazepam, using instead a clonidine TTS-l patch and later a clonidine TTS-2 patch. Before the course of amantadine, the child's symptoms had become progressively less disabling. The exacerbation apparently caused by amantadine was abrupt. It occurred immediately after amantadine was stopped by the mother after 3 days, rather than during the period of active treatment itself. The exacerbation of tics, including sniffing, sighing and gasping noises, and head jerking, was so severe that the child's school teacher urged the patient's mother to take him for urgent medical attention. Apart from these phenomena, his physical examination was found to be normal. At that stage, we changed the medication from the clonidine patch to oral clonidine initially at a dose of 0.05 mg twice a day and then to 0.1 mg twice a day. The tics remained severe for the next 6 weeks then gradually subsided. Amantadine is a synthetic antiviral agent first described by Davies et al. in 1964. Double-blind, placebo controlled studies of amantadine have been performed using patients with naturally occurring and experimentally produced infections resulting from the A2 influenza virus. Statistically significant increases in rates of overall clinical improvement were observed in the patients who received amantadine, compared with those given a placebo (Nagta et aI., 1970). Goodman and Gilman's (1985) text emphasizes that amantadine's prophylactic activity is limited to a single type of a single virus. They also state that "persons with cerebral atherosclerosis, psychiatric disorders, or a history of epilepsy must be observed closely when taking this drug" (p. 1243). Amantadine also releases dopamine from central neurons and facilitates its release by nerve impulses (Van Voigtlander and Moore, 1971). Alterations in striatal dopamine receptor functions have been suggested to underlie the major symptoms of TS (Sandyk, 1989). Such a mechanism could account for the above clinical observations; in this case, exaggerated dopamine receptor supersensitivity after withdrawal of the drug may have been responsible for the exacerbation ofTourette symptoms. Viral infections may themselves alter dopaminergic activity, for example, the postencephalitic Parkinson's syndrome described in young people after the 1918 influenza epidemic. Ac-
371
mother agreed he would normally have shaken off without difficulty. Although he had some history of "taking things hard," including tearfulness, the degree of upset at this time was different. He did not appear otherwise depressed, nor did he acknowledge depressed or irritable feelings. He noted that the wish to die persisted: "I couldn't put it out of my mind." He was distressed at not knowing what to do about this feeling. In the meantime, he noted a decrease in feeling that he had to read sentences over and over. Clomipramine was reduced to 25 mg/day without recurrence of the suicidal ideation during 4 months of follow-up and with complete relief from obsessive and compulsive symptoms. The seriousness of the symptom and its relevance to the possible induction of self-destructive ideation or behavior by fluoxetine make this report of interest. Although fluoxetine and clomipramine are not structurally related, they both increase serotonin activity through blocking reuptake. The possible mechanisms of acute suicidality have been recently debated by King et al. (l99Ia, b) and by Fuller and Beasley (1991). This appears to be the first report of new suicidality in a patient taking clomipramine.
among autistic subjects (Gillberg and Steffenburg, 1987) and of psychosis among epileptics (McKenna et aI., 1985), but an association of the two in monozygotic twins is rare. There has been much discussion of the relations between autism and epilepsy, which seem on the latest evidence to be the outcome of a common cerebral dysfunction (Olsson et aI., 1988). Our cases evidence the concordance in the twins of two pathological conditions (autism and epilepsy), probably of heterogeneous genetic origin with different involvement of genetic and nongenetic factors in the two patients. In both subjects, there was interaction between hereditary factors (family history of psychiatric illness) and homogeneous acquired factors (pre- and perinatal distress). Our report confirms the data of Vukicevic and Siegel (1990) on the primary importance of suboptimal factors in the fetal or neonatal periods to normal neuropsychic development. Similar remarks apply to the multifactorial pathogenesis of epilepsy, for it has recently been recognized that genetic factors are involved even in partial epilepsy (Ottman et aI., 1989). One last point regarding the EEG abnormalities recorded from the left temporal lobe: a left temporal EEG focus is considered to be most frequently associated with psychosis in adults (Perez et aI., 1985).
Gordon Harper, M.D. The Children's Hospital Boston, Massachusetts
Prof. Carlo Lenti Universita Degli Studi Di Milano Milan, Italy
REFERENCES
REFERENCES
Fuller, R. F. & Beasley, C. M., Jr. (1991), Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849 (letter). King, R. A., Riddle, M. A., Chappell, P. B., Hardin, M. T., Anderson, G. M., Lombroso, P. & Scahill, Z. (199Ia), Emergence of selfdestructive phenomena in children and adolescents during fluoxetine treatment. J. Am. Acad. Child Adolesc. Psychiatry, 30: 179-186. - - Anderson, G. M., Rasmusson, A. & Riddle, M. A. (l99Ib), Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849-850 (letter).
Gillberg, C. & Steffenburg, S. (1987), Outcome and prognostic factors in infantile autism and similar conditions. J. Autism Dev. Disord., 17:271-275. McKenna, P. J., Kanej, M. & Parrish, K. (1985), Psychotic syndromes in epilepsy. Am. J. Psychiatry, 142:895-904. Olsson, I., Steffenburg, S. & Gillberg, C. (1988), Epilepsy in autism and autistic-like conditions: a population-based study. Arch. Neural., 45:666-668. Ottman, R., Annegers, J. E., Hauser, W. A. & Kurland, L. T. (1989), Seizure risk in offspring of parents with generalized versus partial epilepsy. Epilepsia, 30:157-161. Perez, M. M., Trimble, M. R., Murray, N. M. F. & Reider, I. (1985), Epileptic psychosis: an evaluation of PSE profiles. Br. J. Psychiatry, 146:155-163. Vukicevic, J., Siegel, B. (1990), Pervasive developmental disorder in monozygotic twins. J. Am. Acad. Child Adolesc. Psychiatry, 29:897-900.
Autism and Epilepsy: Organic Connections? To the Editor: We read with interest the report of Vukicevic and Siegel (1990) on pervasive developmental disorders in monozygotic twins. We report a similar case of autism and epilepsy in male monozygotic twins. Case report: An aunt of the twins' mother suffers from chronic psychosis and is hospitalized in a psychiatric institution. A brother of the father has a primary affective disorder. There was probable fetal damage, as a result of a threatened miscarriage at the 36th week and complete detachment of the placenta at the 39th week, and definite neonatal distress. Born by cesarean section, the first twin presented an Apgar score of 7 at I minute and 9 at 5 minutes; the second twin had a score of 3 at I minute and 5 at 5 minutes. Psychomotor development was delayed in both boys, and they did not learn to walk until 2 years of age. They never learned to speak, and frorv the first years of life, they displayed the characteristic symptoms of autism: lack of social interaction and ability to play, stereotyped behaviors, and so on. The first twin began to have complex partial seizures at age II, and these recurred monthly. The second twin had a similar seizure 8 months later, with a single recurrence after 6 months. Kariotyping with search for fragile X, magnetic resonance imaging, and tests for abnormalities ofthe sugar, amino acid, and mucopolysaccharide metabolism revealed nothing abnormal. Only a CT brain scan revealed signs of atrophy in both twins. EEG showed spike activity over the temporal and central regions of the left hemisphere, more evident in the second twin. Numerous studies have demonstrated a high frequency of epilepsy
370
Biological Liability in Families with Autism To the Editor: Piven et al. (1990, 1991) have provided a well-designed comprehensive study of psychiatric disorders in adult siblings and parents of autistic probands. Our family history studies support their findings, extending the findings to second-degree relatives, which strengthens one hypothesis that some of the psychiatric symptomatology may be an expression of underlying biological liability in families with autism. One study was designed using the mother of the autistic probands as the main informant for autistic probands, siblings, and seconddegree family members, i.e., grandparents, aunts and uncles, nieces and nephews. Family history was obtained using a family history questionnaire that included questions pertaining to medical and psychiatric illness, medication usage, and learning disabilities. When a sibling or other family member was identified, diagnosed, or treated for psychiatric illness, a first-person structured psychiatric interview, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) was conducted (Spitzer and Endicott, 1978). Diagnoses were made using research diagnostic criteria (Spitzer and Robins, 1978). When family members were deceased or unavailable, a secondJ. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992
LETTERS TO THE EDITOR
hand SADS-L structured interview with the mother as informant was completed. Learning disabilities were included when they were diagnosed within the school system and/or by a psychologist. The study included 13 probands (9 white, 4 black; average age, 17.8 ± 9.1 years), 26 first-degree relatives (average age of parents, 44.5 ± 12.1 years, siblings 23.3 ± 13.4 years), and 35 second-degree relatives. The probands had a relatively high rate of using psychoactive medications, 62.5%, at some time during their lives. Psychoactive medication had been prescribed for 33.3% of first-degree relatives and 26.1 % of second-degree relatives. The level of illicit drug abuse, 16% in first-degree relatives and 11 % in second-degree relatives parallels the overall rate of 16% in South Carolina, documented by the South Carolina Commission on Alcohol and Drug Abuse (SCADA). The alcohol abuse rate appears to be high, 38.1 %, in first-degree male and 37.5% in second-degree male relatives. The SCADA rate for male binge drinking on five or more occasions is 17% and for serious problem drinking is 13% in the Southeast. Learning disabilities were diagnosed based on identification within the school system. They were present in 14.3% of first-degree relatives and 12.1 % of second-degree relatives. About a third (34.8%) offirst-degree relatives and 24.2% of seconddegree relatives were classified as having "nerve problems." This closely parallels the 33% rate of psychotropic medication usage in first-degree relatives and 26.1 % in second-degree relatives. In addition, 8% of first-degree relatives and 12% of second-degree relatives had at least one psychiatric hospitalization. In our study, 10.5% of first-degree relatives and 15.6% of seconddegree relatives were diagnosed with anxiety disorder. Only 5% of first-degree relatives and no second-degree relatives had ever had a panic attack, and none were diagnosed with panic disorder. No phobic disorders were diagnosed. Panic and anxiety disorders were diagnosed less frequently in our population than in that of Piven et al. (1990, 1991). Finally, 33.3% of autistic probands, 18.2% of first-degree relatives, and 28.1% of second-degree relatives had been treated for affective disorder. No diagnosis of manic depressive disorder was present. The figures for affective disorder agree with those of Piven et al. (1990, 1991). The number of second-degree family members diagnosed with affective disorders and alcohol problems is higher than would be expected in the general population and similar to that of first-degree family members, i.e., father, mother, and siblings. These findings of a familial aggregation of affective disorder, anxiety disorders, and alcohol problems in both first- and second-degree relatives strengthen and underscore the findings of Piven et al. that these disorders are not entirely the result of raising a handicapped person (Piven et aI., 1990, 1991). Ruth K. Abramson, Ph.D. Harry H. Wright, M.D. Michael L. Cuccaro, Ph.D. Leesa G. Lawrence, M.D. Sheri Babb, M.S. Debbie Pencarinha, M.S. Frederick Marsteller, Ph.D. Elisabeth C. Harris, B.S. University of South Carolina, Columbia REFERENCES
Piven, J., Gayle, J., Chase, G. A., Fink, B., Landa, R., Wzorek, M. & Folstein, S. (1990), A family history study of the adult siblings of autistic individuals. I. Am. Acad. Child Adolesc. Psychiatry, 29:177-184. - - Chase, G. A., Landa, R., Wzorek, M., Gayle, J., Cloud, D. &
I. Am. Acad. Chi/dAdolesc. Psychiatry, 31:2, March 1992
Folstein, S. (1991), Psychiatric disorders in the parents of autistic individuals. I. Am. Acad. Child Adolesc. Psychiatry, 30:471--478. Spitzer, R. L. & Endicott, J. (1978), Schedule for affective disorders and schizophrenia, Ed. 3 (NIMH Clinical Research Branch, Collaborative Program on the Psychology of Depression). Washington, DC: U.S. Government Printing Office. - - & Robins, E. (1978), Research diagnostic criteria. Arch. Gen. Psychiatry, 35:773-82.
A Trigger for Tourette's Syndrome To the Editor: We report the apparent exacerbation of Tourette symptoms by amantadine (Symmetrel®), the antiviral agent prescribed by family practitioners for influenza-like illnesses. The motor and vocal tics as well as the attentional problems of a 9-year-old boy with Tourette's syndrome (TS) whom we had been treating for about 1 year, worsened markedly for 6 weeks after his family practitioner prescribed liquid amantadine (50 mg., three times a day) for him. TS consists of multiple motor and one or more vocal tics that vary with presentation and wax and wane with a duration of at least a year (American Psychiatric Association, 1987). The median age of onset is 7 years, with the great majority of patients experiencing the onset before age 14 years. Males (3:1) are more likely to develop the disorder than females. The onset in our patient was at 7 years of age. His presenting symptoms included neck and shoulder jerking, sniffing, throat clearing, impulsivity, inattention, and hyperactivity. He was diagnosed as having TS by a neurologist shortly after the tics began at age 7 and was treated then with diazepam (1 mg., orally, twice a day) for just over a year. On presentation to our clinic, we decided to taper and discontinue the diazepam, using instead a clonidine TTS-l patch and later a clonidine TTS-2 patch. Before the course of amantadine, the child's symptoms had become progressively less disabling. The exacerbation apparently caused by amantadine was abrupt. It occurred immediately after amantadine was stopped by the mother after 3 days, rather than during the period of active treatment itself. The exacerbation of tics, including sniffing, sighing and gasping noises, and head jerking, was so severe that the child's school teacher urged the patient's mother to take him for urgent medical attention. Apart from these phenomena, his physical examination was found to be normal. At that stage, we changed the medication from the clonidine patch to oral clonidine initially at a dose of 0.05 mg twice a day and then to 0.1 mg twice a day. The tics remained severe for the next 6 weeks then gradually subsided. Amantadine is a synthetic antiviral agent first described by Davies et al. in 1964. Double-blind, placebo controlled studies of amantadine have been performed using patients with naturally occurring and experimentally produced infections resulting from the A2 influenza virus. Statistically significant increases in rates of overall clinical improvement were observed in the patients who received amantadine, compared with those given a placebo (Nagta et aI., 1970). Goodman and Gilman's (1985) text emphasizes that amantadine's prophylactic activity is limited to a single type of a single virus. They also state that "persons with cerebral atherosclerosis, psychiatric disorders, or a history of epilepsy must be observed closely when taking this drug" (p. 1243). Amantadine also releases dopamine from central neurons and facilitates its release by nerve impulses (Van Voigtlander and Moore, 1971). Alterations in striatal dopamine receptor functions have been suggested to underlie the major symptoms of TS (Sandyk, 1989). Such a mechanism could account for the above clinical observations; in this case, exaggerated dopamine receptor supersensitivity after withdrawal of the drug may have been responsible for the exacerbation ofTourette symptoms. Viral infections may themselves alter dopaminergic activity, for example, the postencephalitic Parkinson's syndrome described in young people after the 1918 influenza epidemic. Ac-
371
