- Email: [email protected]
GRAND ROUNDS: SCHIZOPHRENIA OR BIPOLAR?
LETTERS TO THE EDITOR
data suggest that abuse is a risk factor for suicidal behavior in prepubertal children, less is known about the relationship of this risk factor to other risk factors for suicidal behavior in the prepubertal population. Thus, although we have learned a great deal since C. Henry Kempe published his groundbreaking paper titled 'The Battered-Child Syndrome" in 1962, the relative paucity of knowledge about the manifestations of abuse as a risk factor for suicidal behavior in prepubertal children indicates that further research into this area is urgently needed.
In my experience DSM-III-R is quite inadequate for the diagnosis of early bipolar disorder or significant depression with a significant component of anger. Early bipolar disorder often does not include the classicsymptoms of mania. Until we know much more about these disorders in adolescents, the only safe and humane approach to the patient is to do careful, empirical medications trials in the context of overall management and therapy. I hope we will receive a regular follow-up about this patient.
Leslie K. Jacobsen, M.D. Ilene Rabinowitz, M.D. Michele S. Popper, B.A. Robert J. Solomon, M.D. Mae S. Sokol, M.D. Cynthia R. Pfeffer, M.D. The New York Hospital, Cornell Medical Center
Julia F. Moore, M.D. Federal Way, WA
Ceci SJ, Bruck M (1993), Suggestibility of the child witness: a historical review and synthesis. Psychol Bull 113:403-439 de Wilde EJ, Kienhorst ICWM, Diekstra RFW, Woltets WHG (1992), The relationship between adolescent suicidal behavior and life events in childhood and adolescence. Am J Psychiatry 149:45-51 Green AH (1978), Self-destructive behavior in battered children. Am J Psychiatry 135:579-582 Kempe CH, Silverman FN, Steele BF, Droegemueller W, Silver HK (1962), The battered-child syndrome. JAMA 181:17-24 Riggs S, Alario AJ, McHorney C (1990), Health risk behaviors and attempted suicide in adolescents who repott maltreatment. J Pediatr 116:815-821 Stein A, Lewis DO (1992), Discovering physical abuse: insights from a follow-up srudy of delinquents. Child Abuse NegI16:523-531
GRAND ROUNDS: SCHIZOPHRENIA OR BIPOLAR? To the Editor:
I am proposing another psychiatric approach to "Julio's" symptoms as presented in the Grand Rounds article by Sudan et al. (1993). My clinical experience leads me to conclude that usually the diagnosis of schizophrenia should not be made in adolescents or adults until a lithium trial has been performed. If this proves unproductive, I would then undertake an antidepressant trial, usually with a serotonin reuptake inhibitor. These trials do not preclude psychoeducational family therapy and cognitively oriented individual therapy. The family history needs elaboration. Two of his uncles have explosive tempers and are socially isolated and nervous. What is their overall functioning? Could they be bipolar yet have a schizoid personality? The description of the paternal grandmother also requires more detail. Is she depressed? Julio's father has a panic disorder. Is this treated with an antidepressant successfullywithout causing a hypomanic reaction?
j, AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:8 OCTOBER 1994
Sudan R, Setterberg S, Whitaker A, Kestenbaum C (1993), An emerging schizophrenic syndrome. J Am Acad Child Adolesc Psychiatry 32: 1295-130 1
Drs. Whitaker and Kestenbaum reply:
Dr. Moore is concerned that a diagnosis of early bipolar disorder or unipolar depression, rather than schizophrenia, may apply to the 16-year-old patient described. The evidence for and against an affective disorder was discussed in the differential diagnosis and was based on his symptoms and history to that date. As an alternative approach, Dr. Moore suggests using a patient's response to a series of medication trials as a basis for diagnosis. She implies that if Julio were less aggressive during an initial trial of lithium or a serotonin reuptake inhibitor, a diagnosis of a bipolar or unipolar affective disorder, respectively, rather than schizophrenia would be supported. However, such a trial would merely establish that a patient's aggressive behavior responded to a particular medication and would not provide information about any underlying or comorbid disorder. While lithium has been shown to reduce childhood aggression (Alessi et al., 1994), it has not been shown to affect psychotic symptoms. Neuroleptics target more ofthis patient's problem behaviors (aggressive outbursts, bizarre behavior, paranoid ideation, negative symptoms) than either lithium or antidepressants, and would therefore be our first choice for an initial trial of medication. In selecting the type of medication to be used first in this patient, it is also important to distinguish negative symptoms from depressive symptoms. In adults, negative symptoms may respond to neuroleptics but appear not to respond to antidepressants, while depressive symptoms in schizophrenia do respond to antidepressants (Plasky, 1991). While we agree with Dr. Moore that it is often necessary to resort to empirical trials in adolescents, the order in which various medications are tried should be based on the patient's current symptoms and history.
1209
LETTERS TO THE EDITOR
Dr. Moore requests more information on family history. In our view, family history is of dubious value to the differential diagnosis of psychosis in an individual. The occurrence of sporadic cases of schizophrenia as well as variations in the form of psychosis across family generations underscore the complexiry of this issue (Crow, 1986). Given the tendency to misdiagnose adolescents with bipolar disorder as having schizophrenia (see Werry, et aI., 1991 for a review), we appreciate Dr. Moore's concern and welcome this opportunity to provide an update on Julio. He has remained a patient in our own or affiliated treatment facilities and is now 18 years old. Subsequent to our earlier report, he became frankly paranoid and attacked a family member. He was hospitalized for 8 weeks as an inpatient and stabilized on Haldol® (haloperidol) and Cogentin® (benztropine mesylate). He was then discharged to our day treatment program. He was transferred to a longer-term day treatment facility and then to a special high school, but his attendance remained poor. He was readmitted to our day program, where his attendance and socialization improved. He is currently attending a vocational program and an adult day treatment program in our neighborhood. Since beginning neuroleptic therapy, he has had no further aggressive outbursts, paranoid ideation, or bizarre behavior. There have been no behaviors consistent with hypomania or mania during the follow-up period, nor has Julio evidenced signs or symptoms of depression. Negative symptoms including anergy, Rat affect, and poverty of speech have been most prominent. A trial of an atypical neuroleptic such as clozapine (Birmaher, 1992) to ameliorate his negative symptoms is planned. Agnes H. Whitaker, M.D. Clarice Kestenbaum, M.D. Columbia University, New York, NY Alessi N, Naylor MW, Ghaziuddin M, Zubietta ]K (1994), Update on lithium carbonate therapy in children and adolescents. JAm Acad Child
Ado/esc Psychiatry 33:291-304 Birmaher B (1992), Clozapine for the treatment of adolescents with schizophrenia. JAm Acad Child Ado/esc Psychiatry 31: 160-164 Crow T] (1986), The continuum of psychosis and its implication for the structure of the gene. Br J Psychiatry 149:419-429 Plasky P (1991), Antidepressant usage in schizophrenia. Schizophr Bull 17:649-657 Werry ]S, McClellan ]M, Chard L (1991), Childhood and adolescent schizophrenia, bipolar and schizoaffective disorders: a clinical and outcome study. JAm Acad Child Ado/esc Psychiatry 30:457-465
sleep disturbances associated with ADHD. I was pleased to see this report as I have had similar experience using clonidine in this way for several hundred ADHD patients. Clonidine is being used with greater frequency to treat sleep disorders in my community. I would like to offer an observed adverse effect that was not included in their report. This is a rebound hyperarousal in the middle of the night after the bedtime clonidine dose wears off, typically 4 to 5 hours after the bedtime dose is given. This may manifest as simply wakening, or as more troublesome nightmares, and even as night terrors. Roughly 20% of cases experience this adverse effect. When the patient is a child, this rebound can result in an anxious child showing up in the parents' bedroom every night like clockwork. I have seen this problem misinterpreted as a behavioral problem and dealt with as such, when it was clearly an unrecognized adverse effect of the medication. I have effectively solved this problem for my patients in virtually every case where it has occurred by using an extended-release form of clonidine. This is not presently available from any manufacturer, but. can be prepared by a local pharmacist by compounding clonidine with a hydroxypropylmethylcellulose extended-release polymer to release over an 8-hour period. Usually 0.1 or 0.2 mg given several hours before bedtime works very well. My own clinical experience with this extended-release preparation in several hundred patients is that it is reliable, effective, and safe. Another alternative that I have found effective is the use of Tenex® (guanfacine), which has a longer half-life and does not appear to result in rebound arousal problems in the middle of the night. Doses of 1.0 or 2.0 mg several hours before bedtime usually work very well. Extended-release clonidine capsules and T enex are not typically as effective as clonidine tablets in aiding the onset of sleep. For this reason I have often added a dose of clonidine in regular tablet form an hour before bedtime. The rapid absorption and peak effect of clonidine an hour after the dose aids in the onset of sleep, and the longeracting medication maintains sleep through the night. Again, I very much appreciate the contributions of the authors. I hope my comments will stimulate further inquiry into the adverse effect of rebound hyperarousal in the middle of the night and possible solutions for this problem.
EXTENDED-RELEASE CLONIDINE FOR SLEEP DISORDERS
H. Joseph Horacek, M.D. Charlotte, NC
To the Editor:
In the March/April issue of the Journal, Wilens et al. reported on their clinical experience in using clonidine for
1210
Wilens TE, Biederman], Spencer T (1994), Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder. JAm AcadChild
AM/esc Psychiatry 33:424-426
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY. 33:8, OCTOBER 1994
data suggest that abuse is a risk factor for suicidal behavior in prepubertal children, less is known about the relationship of this risk factor to other risk factors for suicidal behavior in the prepubertal population. Thus, although we have learned a great deal since C. Henry Kempe published his groundbreaking paper titled 'The Battered-Child Syndrome" in 1962, the relative paucity of knowledge about the manifestations of abuse as a risk factor for suicidal behavior in prepubertal children indicates that further research into this area is urgently needed.
In my experience DSM-III-R is quite inadequate for the diagnosis of early bipolar disorder or significant depression with a significant component of anger. Early bipolar disorder often does not include the classicsymptoms of mania. Until we know much more about these disorders in adolescents, the only safe and humane approach to the patient is to do careful, empirical medications trials in the context of overall management and therapy. I hope we will receive a regular follow-up about this patient.
Leslie K. Jacobsen, M.D. Ilene Rabinowitz, M.D. Michele S. Popper, B.A. Robert J. Solomon, M.D. Mae S. Sokol, M.D. Cynthia R. Pfeffer, M.D. The New York Hospital, Cornell Medical Center
Julia F. Moore, M.D. Federal Way, WA
Ceci SJ, Bruck M (1993), Suggestibility of the child witness: a historical review and synthesis. Psychol Bull 113:403-439 de Wilde EJ, Kienhorst ICWM, Diekstra RFW, Woltets WHG (1992), The relationship between adolescent suicidal behavior and life events in childhood and adolescence. Am J Psychiatry 149:45-51 Green AH (1978), Self-destructive behavior in battered children. Am J Psychiatry 135:579-582 Kempe CH, Silverman FN, Steele BF, Droegemueller W, Silver HK (1962), The battered-child syndrome. JAMA 181:17-24 Riggs S, Alario AJ, McHorney C (1990), Health risk behaviors and attempted suicide in adolescents who repott maltreatment. J Pediatr 116:815-821 Stein A, Lewis DO (1992), Discovering physical abuse: insights from a follow-up srudy of delinquents. Child Abuse NegI16:523-531
GRAND ROUNDS: SCHIZOPHRENIA OR BIPOLAR? To the Editor:
I am proposing another psychiatric approach to "Julio's" symptoms as presented in the Grand Rounds article by Sudan et al. (1993). My clinical experience leads me to conclude that usually the diagnosis of schizophrenia should not be made in adolescents or adults until a lithium trial has been performed. If this proves unproductive, I would then undertake an antidepressant trial, usually with a serotonin reuptake inhibitor. These trials do not preclude psychoeducational family therapy and cognitively oriented individual therapy. The family history needs elaboration. Two of his uncles have explosive tempers and are socially isolated and nervous. What is their overall functioning? Could they be bipolar yet have a schizoid personality? The description of the paternal grandmother also requires more detail. Is she depressed? Julio's father has a panic disorder. Is this treated with an antidepressant successfullywithout causing a hypomanic reaction?
j, AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 33:8 OCTOBER 1994
Sudan R, Setterberg S, Whitaker A, Kestenbaum C (1993), An emerging schizophrenic syndrome. J Am Acad Child Adolesc Psychiatry 32: 1295-130 1
Drs. Whitaker and Kestenbaum reply:
Dr. Moore is concerned that a diagnosis of early bipolar disorder or unipolar depression, rather than schizophrenia, may apply to the 16-year-old patient described. The evidence for and against an affective disorder was discussed in the differential diagnosis and was based on his symptoms and history to that date. As an alternative approach, Dr. Moore suggests using a patient's response to a series of medication trials as a basis for diagnosis. She implies that if Julio were less aggressive during an initial trial of lithium or a serotonin reuptake inhibitor, a diagnosis of a bipolar or unipolar affective disorder, respectively, rather than schizophrenia would be supported. However, such a trial would merely establish that a patient's aggressive behavior responded to a particular medication and would not provide information about any underlying or comorbid disorder. While lithium has been shown to reduce childhood aggression (Alessi et al., 1994), it has not been shown to affect psychotic symptoms. Neuroleptics target more ofthis patient's problem behaviors (aggressive outbursts, bizarre behavior, paranoid ideation, negative symptoms) than either lithium or antidepressants, and would therefore be our first choice for an initial trial of medication. In selecting the type of medication to be used first in this patient, it is also important to distinguish negative symptoms from depressive symptoms. In adults, negative symptoms may respond to neuroleptics but appear not to respond to antidepressants, while depressive symptoms in schizophrenia do respond to antidepressants (Plasky, 1991). While we agree with Dr. Moore that it is often necessary to resort to empirical trials in adolescents, the order in which various medications are tried should be based on the patient's current symptoms and history.
1209
LETTERS TO THE EDITOR
Dr. Moore requests more information on family history. In our view, family history is of dubious value to the differential diagnosis of psychosis in an individual. The occurrence of sporadic cases of schizophrenia as well as variations in the form of psychosis across family generations underscore the complexiry of this issue (Crow, 1986). Given the tendency to misdiagnose adolescents with bipolar disorder as having schizophrenia (see Werry, et aI., 1991 for a review), we appreciate Dr. Moore's concern and welcome this opportunity to provide an update on Julio. He has remained a patient in our own or affiliated treatment facilities and is now 18 years old. Subsequent to our earlier report, he became frankly paranoid and attacked a family member. He was hospitalized for 8 weeks as an inpatient and stabilized on Haldol® (haloperidol) and Cogentin® (benztropine mesylate). He was then discharged to our day treatment program. He was transferred to a longer-term day treatment facility and then to a special high school, but his attendance remained poor. He was readmitted to our day program, where his attendance and socialization improved. He is currently attending a vocational program and an adult day treatment program in our neighborhood. Since beginning neuroleptic therapy, he has had no further aggressive outbursts, paranoid ideation, or bizarre behavior. There have been no behaviors consistent with hypomania or mania during the follow-up period, nor has Julio evidenced signs or symptoms of depression. Negative symptoms including anergy, Rat affect, and poverty of speech have been most prominent. A trial of an atypical neuroleptic such as clozapine (Birmaher, 1992) to ameliorate his negative symptoms is planned. Agnes H. Whitaker, M.D. Clarice Kestenbaum, M.D. Columbia University, New York, NY Alessi N, Naylor MW, Ghaziuddin M, Zubietta ]K (1994), Update on lithium carbonate therapy in children and adolescents. JAm Acad Child
Ado/esc Psychiatry 33:291-304 Birmaher B (1992), Clozapine for the treatment of adolescents with schizophrenia. JAm Acad Child Ado/esc Psychiatry 31: 160-164 Crow T] (1986), The continuum of psychosis and its implication for the structure of the gene. Br J Psychiatry 149:419-429 Plasky P (1991), Antidepressant usage in schizophrenia. Schizophr Bull 17:649-657 Werry ]S, McClellan ]M, Chard L (1991), Childhood and adolescent schizophrenia, bipolar and schizoaffective disorders: a clinical and outcome study. JAm Acad Child Ado/esc Psychiatry 30:457-465
sleep disturbances associated with ADHD. I was pleased to see this report as I have had similar experience using clonidine in this way for several hundred ADHD patients. Clonidine is being used with greater frequency to treat sleep disorders in my community. I would like to offer an observed adverse effect that was not included in their report. This is a rebound hyperarousal in the middle of the night after the bedtime clonidine dose wears off, typically 4 to 5 hours after the bedtime dose is given. This may manifest as simply wakening, or as more troublesome nightmares, and even as night terrors. Roughly 20% of cases experience this adverse effect. When the patient is a child, this rebound can result in an anxious child showing up in the parents' bedroom every night like clockwork. I have seen this problem misinterpreted as a behavioral problem and dealt with as such, when it was clearly an unrecognized adverse effect of the medication. I have effectively solved this problem for my patients in virtually every case where it has occurred by using an extended-release form of clonidine. This is not presently available from any manufacturer, but. can be prepared by a local pharmacist by compounding clonidine with a hydroxypropylmethylcellulose extended-release polymer to release over an 8-hour period. Usually 0.1 or 0.2 mg given several hours before bedtime works very well. My own clinical experience with this extended-release preparation in several hundred patients is that it is reliable, effective, and safe. Another alternative that I have found effective is the use of Tenex® (guanfacine), which has a longer half-life and does not appear to result in rebound arousal problems in the middle of the night. Doses of 1.0 or 2.0 mg several hours before bedtime usually work very well. Extended-release clonidine capsules and T enex are not typically as effective as clonidine tablets in aiding the onset of sleep. For this reason I have often added a dose of clonidine in regular tablet form an hour before bedtime. The rapid absorption and peak effect of clonidine an hour after the dose aids in the onset of sleep, and the longeracting medication maintains sleep through the night. Again, I very much appreciate the contributions of the authors. I hope my comments will stimulate further inquiry into the adverse effect of rebound hyperarousal in the middle of the night and possible solutions for this problem.
EXTENDED-RELEASE CLONIDINE FOR SLEEP DISORDERS
H. Joseph Horacek, M.D. Charlotte, NC
To the Editor:
In the March/April issue of the Journal, Wilens et al. reported on their clinical experience in using clonidine for
1210
Wilens TE, Biederman], Spencer T (1994), Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder. JAm AcadChild
AM/esc Psychiatry 33:424-426
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY. 33:8, OCTOBER 1994