Case Study Buspirone-Associated Mental Status Changes POONAM SONI, M.D.,
AND
ARDEN L. WEINTRAUB, M.D.
Abstract. The pharmacological management of anxiety in children primarily has used antidepressants, such as imipramine. Buspirone, an atypical anxiolytic, has been shown to be of benefit in both adults and children. It has relatively few side effects and is generally well tolerated. Two cases are reported here involving children treated for anxiety with buspirone who subsequently suffered a possible psychotic deterioration. J. Am. Acad. Child Adolesc. Psychiatry, 1992,31,6:1098-1099. Key Words: buspirone, children, psychosis, aggression, pharmacotherapy. Buspirone is an unusual anxiolytic; its mechanism of action is not well understood. However, it displays affinity for dopamine receptors and for serotonin (5-HT) type 1 receptors in the hippocampus (Eison and Temple, 1986). Buspirone has been used clinically in the treatment of anxiety in diverse patient populations, including those with autism (Realmuto et aI., 1989), schizophrenia (Brody et aI., 1990; Goff et aI., 1991; Sathananthan et aI., 1975; Sovner and Parnell-Sovner, 1989), mental retardation with aggression (Ratey et aI., 1989), and brain injury with secondary agitation (Levine, 1988). Responses generally have been favorable with reduction in anxiety, agitation, and aggression. In four published cases, buspirone was noted to precipitate mania (Liegghio and Yeragani, 1988; McDaniel et aI., 1990; McIvor and Sinanan, 1991; Price and Bielefeld, 1989). The use of buspirone in schizophrenia has resulted in inconsistent findings, regardless of concomitant neuroleptic use. In one study, positive symptoms increased in two of seven patients; negative symptoms increased in one patient (Brody et aI., 1990). To the authors' knowledge, the following cases are the first reported examples of possible adverse reactions to buspirone in children.
Case 1 A.M. is a 12-year-old white girl raised in a home marked by severe physical abuse and nutritional neglect. (Her mother suffered from an unspecified seizure disorder and polysubstance abuse, primarily cocaine abuse. Her biological father was unknown.) She was removed from her natural mother at age 10 and placed in therapeutic foster care. She was diagnosed via clinical interview with attention-deficit Accepted June 15, 1992. Drs. Soni and Weintraub are staffchild and adolescent psychiatrists with Valley Mental Health's Adolescent Residential Treatment and Education Center, Kearns, Utah. Dr. Soni is also a staff psychiatrist at Primary Children's Medical Center and a limited-term clinical instructor at the University ofUtah School ofMedicine. Dr. Weintraub is a clinical instructor at the University of Utah School of Medicine, Department of Psychiatry. Reprint requests to Dr. Soni, ARTEC, 3809 West 6200 South, Building F, Kearns, UT 84118. 0890-8567/92/3106-1O98$03.00/0© 1992 by the American Academy of Child and Adolescent Psychiatry.
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hyperactivity disorder and pervasive developmental disorder not otherwise specified. She was treated with methylphenidate 15mg tid with notable improvement in her ability to remain on task and complete school work. AM. initially began visitation with her mother under supervised conditions. She tolerated visitation well. As AM. moved closer toward unsupervised visits with her mother, she became more anxious. When questioned, AM. stated that she was afraid the visits might be revoked if either she or her mother made any mistakes. A.M. was placed on buspirone 5 mg q day for 4 days. This was increased to buspirone 5 mg bid. On the addition of buspirone, AM.' s foster parents reported that she became unusually whiny and irritable. She also manifested loose associations and thought blocking. At one point, A.M. poured a glass of juice and bit the glass, causing the glass to shatter. She had one piece of glass in her mouth, which she spit out without injury. When questioned she could not give a reason for the odd behavior. The buspirone was discontinued. She returned to baseline within 24 hours. At successive examinations over 2 months, AM. has shown continued improvement in her school behavior and her level of anxiety despite unsupervised visits with her mother.
Case 2 E.H. is an 11-year-old white boy, the eldest of four children, who was raised by a physically abusive father. He and his siblings were removed from their parents due to the children's odd behaviors and concerns that the parents placed their children at risk physically. The family history revealed the father had symptoms of paranoia, delusional thinking, and severe identity disturbance. Owing to his refusal to be evaluated psychiatrically, a formal diagnosis has not been established. His judgment is severely impaired. As an example, he reported he had taught all four children to "shoot to kill" with a gun, including the youngest child who was 4 years old. The mother has a history of an old head injury as well as a seizure disorder. In foster care, RH. was noted to manifest bizarre behavior including inappropriate sexual behavior, acting like an animal (crawling on the floor like a dog and wriggling and hissing like a snake), and wandering at night. He was diagnosed via clinical interview with post traumatic stress disorJ. Am. Acad. Child Adolesc. Psychiatry, 31:6, November 1992
BUSPIRONE-ASSOCIATED MENTAL STATUS CHANGES
der (provisional, rule out psychotic disorder not otherwise specified). He was placed on thioridazine and was stabilized on 125 mg per day with resolution of the symptoms. E.H. and his siblings continued to have supervised visits with their parents on a biweekly basis for one hour. These visits were extremely stressful. E.H. became much more nervous and anxious when he talked with or about his parents. He was placed on buspirone 5 mg q day. After buspirone was initiated, E.H.' s foster mother noted that E.H. became more aggressive. When the dosage was increased to buspirone 5 mg bid, he began to hiss like a snake, laugh uncontrollably, hit his head with his hands, pass gas inappropriately, and stand still holding his hands in front of him while humming. The buspirone was discontinued. His symptoms resolved after 3 days. There has been no recurrence of these symptoms despite the stress of moving toward unsupervised visits with his parents and a recent change in foster home placement. Discussion These two cases are presented as examples of possible adverse reactions to buspirone in children. There is now one case report of buspirone possibly inducing a psychotic reaction in an adult patient with schizotypal personality disorder (Friedman, 1991). By May 1991, Bristol-Meyers Squibb had received a total of eight reports of possible psychotic reactions associated with the use of buspirone. Bristol-Meyers Squibb was recontacted in February 1992 (personal communication). At that time, they reported fewer than 20 cases of psychoses associated with buspirone use. The ages of the patients were not available. The effects of buspirone are diverse. In addition to its effect of decreasing 5-HT activity, it also increases dopaminergic and noradrenergic activity. Other neurotransmitters affected are acetylcholine and gamma-aminobutyric acid (Eison, 1989). A study of children and adolescents with disruptive behaviors suggests a relationship with low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, a metabolite of 5-HT (Kruesi et aI., 1990). It is possible that the bizarre behaviors in these two cases were due to lowered 5-HT levels in the cerebrospinal fluid secondary to buspirone administration.
J. Am. Acad. Child Adolesc. Psychiatry, 31:6, November 1992
However, it is also possible these behaviors resulted from an alteration in dopaminergic and/or noradrenergic systems, as manipulation of these systems has been reported to enhance aggressive behaviors (Eison, 1989). Although buspirone has been found useful in children, it appears that in certain individuals it may aggravate an underlying predisposition to psychosis and/or aggression. References Brody, D., Adler, L. A., Kim, T., Angrist, B. & Rotrosen, J. (1990), Effects of buspirone in seven schizophrenic subjects (letter). J. Clin. Psychopharmacol., 10:68-69. Eison, A. S. & Temple, Jr., D. L. (1986), Buspirone: review of its pharmacology and current perspectives on its mechanism of action. Am. J. Med., 80(suppl. 3B):1-9. Eison, M. S. (1989), The new generation of serotonergic anxiolytics: possible clinical roles. Psychopathology, 22(suppl. 1): 13-20. Friedman, R. (1991), Possible induction of psychosis by buspirone (letter). Am. J. Psychiatry, 148: 1606. Goff, D. C., Midha, K K, Brotman, A. W., McCormick, S., Waites, M. & Amico, E. T. (1991), An open trial of buspirone added to neuroleptics in schizophrenic patients. J. Clin. Psychopharmacol., 11:193-197. Kruesi, M. J. P., Rappaport, J. L., Hamburger, S. et al. (1990), Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents. Arch. Gen. Psychiatry, 47:419-426. Levine, A. M. (1988), Buspirone and agitation in head injury. Brain Inj., 2:165-167. Liegghio, N. E. & Yeragani, V. K (1988), Buspirone-induced hypomania: a case report (letter). J. Clin. Psychopharmacol., 8:226-227. McDaniel, J. S., Ninan, P. T. & Magnuson, J. V. (1990), Possible induction of mania by buspirone (letter). Am. J. Psychiatry, 147:125-126. McIvor, R. J. & Sinanan, K (1991), Buspirone-induced mania (letter). Br. J. Psychiatry, 158: 136-137. Price, W. A. & Bielefeld, M. (1989), Buspirone-induced mania (letter). J. Clin. Psychopharmacol., 9: 150-151. Ratey, J. J., Sovner, R., Mikkelsen, E. & Chmielinski, H. E. (1989), Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons. J. Clin. Psychiatry, 50:382-384. Realmuto, G. M., August, G. 1. & Garfinkel, B. D. (1989), Clinical effect of buspirone in autistic children. J. Clin. Psychopharmacol., 9:122-125. Sathananthan, G. L., Sanghvi, I., Phillips, N. & Gershon, S. (1975), MJ 9022: correlation between neuroleptic potential and stereotypy. Curro Ther. Res., 18:701-705. Sovner, R. & Parnell-Sovner, N. (1989), Use of buspirone in the treatment of schizophrenia (letter). J. Clin. Psychopharamcol., 9:61-62.
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AND
ARDEN L. WEINTRAUB, M.D.
Abstract. The pharmacological management of anxiety in children primarily has used antidepressants, such as imipramine. Buspirone, an atypical anxiolytic, has been shown to be of benefit in both adults and children. It has relatively few side effects and is generally well tolerated. Two cases are reported here involving children treated for anxiety with buspirone who subsequently suffered a possible psychotic deterioration. J. Am. Acad. Child Adolesc. Psychiatry, 1992,31,6:1098-1099. Key Words: buspirone, children, psychosis, aggression, pharmacotherapy. Buspirone is an unusual anxiolytic; its mechanism of action is not well understood. However, it displays affinity for dopamine receptors and for serotonin (5-HT) type 1 receptors in the hippocampus (Eison and Temple, 1986). Buspirone has been used clinically in the treatment of anxiety in diverse patient populations, including those with autism (Realmuto et aI., 1989), schizophrenia (Brody et aI., 1990; Goff et aI., 1991; Sathananthan et aI., 1975; Sovner and Parnell-Sovner, 1989), mental retardation with aggression (Ratey et aI., 1989), and brain injury with secondary agitation (Levine, 1988). Responses generally have been favorable with reduction in anxiety, agitation, and aggression. In four published cases, buspirone was noted to precipitate mania (Liegghio and Yeragani, 1988; McDaniel et aI., 1990; McIvor and Sinanan, 1991; Price and Bielefeld, 1989). The use of buspirone in schizophrenia has resulted in inconsistent findings, regardless of concomitant neuroleptic use. In one study, positive symptoms increased in two of seven patients; negative symptoms increased in one patient (Brody et aI., 1990). To the authors' knowledge, the following cases are the first reported examples of possible adverse reactions to buspirone in children.
Case 1 A.M. is a 12-year-old white girl raised in a home marked by severe physical abuse and nutritional neglect. (Her mother suffered from an unspecified seizure disorder and polysubstance abuse, primarily cocaine abuse. Her biological father was unknown.) She was removed from her natural mother at age 10 and placed in therapeutic foster care. She was diagnosed via clinical interview with attention-deficit Accepted June 15, 1992. Drs. Soni and Weintraub are staffchild and adolescent psychiatrists with Valley Mental Health's Adolescent Residential Treatment and Education Center, Kearns, Utah. Dr. Soni is also a staff psychiatrist at Primary Children's Medical Center and a limited-term clinical instructor at the University ofUtah School ofMedicine. Dr. Weintraub is a clinical instructor at the University of Utah School of Medicine, Department of Psychiatry. Reprint requests to Dr. Soni, ARTEC, 3809 West 6200 South, Building F, Kearns, UT 84118. 0890-8567/92/3106-1O98$03.00/0© 1992 by the American Academy of Child and Adolescent Psychiatry.
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hyperactivity disorder and pervasive developmental disorder not otherwise specified. She was treated with methylphenidate 15mg tid with notable improvement in her ability to remain on task and complete school work. AM. initially began visitation with her mother under supervised conditions. She tolerated visitation well. As AM. moved closer toward unsupervised visits with her mother, she became more anxious. When questioned, AM. stated that she was afraid the visits might be revoked if either she or her mother made any mistakes. A.M. was placed on buspirone 5 mg q day for 4 days. This was increased to buspirone 5 mg bid. On the addition of buspirone, AM.' s foster parents reported that she became unusually whiny and irritable. She also manifested loose associations and thought blocking. At one point, A.M. poured a glass of juice and bit the glass, causing the glass to shatter. She had one piece of glass in her mouth, which she spit out without injury. When questioned she could not give a reason for the odd behavior. The buspirone was discontinued. She returned to baseline within 24 hours. At successive examinations over 2 months, AM. has shown continued improvement in her school behavior and her level of anxiety despite unsupervised visits with her mother.
Case 2 E.H. is an 11-year-old white boy, the eldest of four children, who was raised by a physically abusive father. He and his siblings were removed from their parents due to the children's odd behaviors and concerns that the parents placed their children at risk physically. The family history revealed the father had symptoms of paranoia, delusional thinking, and severe identity disturbance. Owing to his refusal to be evaluated psychiatrically, a formal diagnosis has not been established. His judgment is severely impaired. As an example, he reported he had taught all four children to "shoot to kill" with a gun, including the youngest child who was 4 years old. The mother has a history of an old head injury as well as a seizure disorder. In foster care, RH. was noted to manifest bizarre behavior including inappropriate sexual behavior, acting like an animal (crawling on the floor like a dog and wriggling and hissing like a snake), and wandering at night. He was diagnosed via clinical interview with post traumatic stress disorJ. Am. Acad. Child Adolesc. Psychiatry, 31:6, November 1992
BUSPIRONE-ASSOCIATED MENTAL STATUS CHANGES
der (provisional, rule out psychotic disorder not otherwise specified). He was placed on thioridazine and was stabilized on 125 mg per day with resolution of the symptoms. E.H. and his siblings continued to have supervised visits with their parents on a biweekly basis for one hour. These visits were extremely stressful. E.H. became much more nervous and anxious when he talked with or about his parents. He was placed on buspirone 5 mg q day. After buspirone was initiated, E.H.' s foster mother noted that E.H. became more aggressive. When the dosage was increased to buspirone 5 mg bid, he began to hiss like a snake, laugh uncontrollably, hit his head with his hands, pass gas inappropriately, and stand still holding his hands in front of him while humming. The buspirone was discontinued. His symptoms resolved after 3 days. There has been no recurrence of these symptoms despite the stress of moving toward unsupervised visits with his parents and a recent change in foster home placement. Discussion These two cases are presented as examples of possible adverse reactions to buspirone in children. There is now one case report of buspirone possibly inducing a psychotic reaction in an adult patient with schizotypal personality disorder (Friedman, 1991). By May 1991, Bristol-Meyers Squibb had received a total of eight reports of possible psychotic reactions associated with the use of buspirone. Bristol-Meyers Squibb was recontacted in February 1992 (personal communication). At that time, they reported fewer than 20 cases of psychoses associated with buspirone use. The ages of the patients were not available. The effects of buspirone are diverse. In addition to its effect of decreasing 5-HT activity, it also increases dopaminergic and noradrenergic activity. Other neurotransmitters affected are acetylcholine and gamma-aminobutyric acid (Eison, 1989). A study of children and adolescents with disruptive behaviors suggests a relationship with low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, a metabolite of 5-HT (Kruesi et aI., 1990). It is possible that the bizarre behaviors in these two cases were due to lowered 5-HT levels in the cerebrospinal fluid secondary to buspirone administration.
J. Am. Acad. Child Adolesc. Psychiatry, 31:6, November 1992
However, it is also possible these behaviors resulted from an alteration in dopaminergic and/or noradrenergic systems, as manipulation of these systems has been reported to enhance aggressive behaviors (Eison, 1989). Although buspirone has been found useful in children, it appears that in certain individuals it may aggravate an underlying predisposition to psychosis and/or aggression. References Brody, D., Adler, L. A., Kim, T., Angrist, B. & Rotrosen, J. (1990), Effects of buspirone in seven schizophrenic subjects (letter). J. Clin. Psychopharmacol., 10:68-69. Eison, A. S. & Temple, Jr., D. L. (1986), Buspirone: review of its pharmacology and current perspectives on its mechanism of action. Am. J. Med., 80(suppl. 3B):1-9. Eison, M. S. (1989), The new generation of serotonergic anxiolytics: possible clinical roles. Psychopathology, 22(suppl. 1): 13-20. Friedman, R. (1991), Possible induction of psychosis by buspirone (letter). Am. J. Psychiatry, 148: 1606. Goff, D. C., Midha, K K, Brotman, A. W., McCormick, S., Waites, M. & Amico, E. T. (1991), An open trial of buspirone added to neuroleptics in schizophrenic patients. J. Clin. Psychopharmacol., 11:193-197. Kruesi, M. J. P., Rappaport, J. L., Hamburger, S. et al. (1990), Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents. Arch. Gen. Psychiatry, 47:419-426. Levine, A. M. (1988), Buspirone and agitation in head injury. Brain Inj., 2:165-167. Liegghio, N. E. & Yeragani, V. K (1988), Buspirone-induced hypomania: a case report (letter). J. Clin. Psychopharmacol., 8:226-227. McDaniel, J. S., Ninan, P. T. & Magnuson, J. V. (1990), Possible induction of mania by buspirone (letter). Am. J. Psychiatry, 147:125-126. McIvor, R. J. & Sinanan, K (1991), Buspirone-induced mania (letter). Br. J. Psychiatry, 158: 136-137. Price, W. A. & Bielefeld, M. (1989), Buspirone-induced mania (letter). J. Clin. Psychopharmacol., 9: 150-151. Ratey, J. J., Sovner, R., Mikkelsen, E. & Chmielinski, H. E. (1989), Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons. J. Clin. Psychiatry, 50:382-384. Realmuto, G. M., August, G. 1. & Garfinkel, B. D. (1989), Clinical effect of buspirone in autistic children. J. Clin. Psychopharmacol., 9:122-125. Sathananthan, G. L., Sanghvi, I., Phillips, N. & Gershon, S. (1975), MJ 9022: correlation between neuroleptic potential and stereotypy. Curro Ther. Res., 18:701-705. Sovner, R. & Parnell-Sovner, N. (1989), Use of buspirone in the treatment of schizophrenia (letter). J. Clin. Psychopharamcol., 9:61-62.
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