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The Concurrent Use of Lithium and Methylphenidate in a Child
Case Study
•
The Concurrent Use of Lithium and Methylphenidate in a Child WILLIAM L. LICAMELE, M.D.,
AND
RICHARD L. GOLDBERG, M.D.
Abstract. The case of a young boy with symptoms of both attention deficit and affective disorders is presented. The patient was successfully treated witha combination of lithium and methylphenidate. Issues about comorbidity and polypharmacy in children are raised, and the concommitant useofIithium and methylphenidate in a childisdiscussed. 1. Am. Acad. Child Adolesc. Psychiatry, 1989, 28, 5:785-787. Key Words: methylphenidate, lithium, attention deficit disorder. Coadministration of two or more psychopharmacologic agents in children, as in adults, runs the risk of augmenting or attenuating either the therapeutic or the adverse effects of each agent. Polypharmacy is sometimes justified, however, when comorbid disorders occur. This is a common occurrence in childen in whom symptoms indicative of attention deficit disorder (ADD) coexist with affective symptomatology. Because the study ofcomorbidity and polypharmacy in juveniles is a relatively new field and there are few reported studies that offer guidance, clinicians must exercise caution, especially in areas where the possible side effects of polypharmacy on the developing child are uncertain. Given the special complexities in the treatment of childhood disorders, polypharmacy should be attempted only when the seriousness of the situation mandates such measures, e.g. to avoid hospitalization or to prevent self-injury. This paper describes the concurrent use of methylphenidate and lithium in a young child who manifests symptoms which might indicate the presence of comorbid disorders. Few studies have specifically addressed the question of whether affective disorders are primary or secondary to other disorders in children. Carlson and and Cantwell (1979) were among the first to distinguish primary vs. secondary affective disorders in juveniles. They found that 50% of all affective disorders were secondary and that 50% of these secondary disorders coexisted with "hyperactivity." Dyson and Barcal (1970) concluded that some children with early "hyperactivity" and a family history of bipolar disorder were actually manifesting early symptoms of bipolar disorder. These children were differentiated from hyperactive children in non bipolar families by a lack of soft signs and a failure to respond to stimulants. Family studies of hyperactive children (Morrison and Stewart, 1971) have not found a higher incidence of affective
disorders. However, in those studies, nonresponders to stimulants did have a higher incidence of affective disorders in their families. Robbins (1966), who studied long-term followup of hyperactive children, did not find a greater prevalence of adult bipolar disorders than would be expected in the general population. Lithium Treatment of Children and Adolescents Literature exists on the use oflithium for ADHD as well as for conduct or aggressive symptoms. Greenhill et al. (1973) used lithium in the treatment of severely hyperactive children who had not responded to stimulants and found either no effect or a worsening of target symptoms. Dostal (1972) treated severely disturbed, retarded, aggressive adolescents with lithium and reported that it alleviated anger, aggression, and hyperactivity. However, patients whose hyperkinetic behavior lacked an affective component did not show improvement. Delong and Nieman (1983), as summarized by Campbell et al. (1985), found that 16 children and adolescents who had previously had favorable responses to lithium responded positively in a double-blind discontinuation trial of lithium. Eleven of the 16 had been tested with stimulants for ADD on a prior occasion, and although the subjects benefited from lithium, the ADD symptoms did not improve. In a lithium trial with a sample of 196 children and adolescents, Delong and Aldershof (1987) reported that lithium was effective in 82% of subjects with emotionally unstable character disorder, 66% of subjects with bipolar affective disorder, and 71 % of children of lithium-responsive parents. Lithium was effective for ADD only in subjects with associated affective symptoms (38%), and in 11 of 19 such patients lithium worsened symptoms of ADD. On the other hand, Campbell (1984) reported a positive response to lithium in "hyper-aggressive children." In that double-blind study of 61 boys, both Haldol'" and Lithium" were found to equally decrease aggressiveand other conduct symptoms but Lithium had fewer side effects. Gastfriend et al. (1984) tried desipramine (an antidepressant and second line drug for ADD) with 12 adolescents with ADD who had not responded to stimulants. The authors reported that 11 of the 12 had a favorable response within a month. According to a table accompanying the report, one patient had a codiagnosis of depression and two were on lithium. The report did not explain why two patients were taking lithium
Accepted February 22. 1989. Dr. Licamele is Clinical Professor ofPsychiatry and Pediatrics and Director ofChild and Adolescent Psychiatric Services. and Dr. Goldberg is Acting Chairman. Department of Psychiatry, Georgetown University Hospital. Washington. D.C. Reprint requests to Dr. Licamele, Dept. of Psychiatry, Georgetown University Hospital, 3800 Reservoir Road. N. w.. Washington, DC 20007. 0890-8567/89/2805-0785$02.00/0© 1989 by the American Acad-
emy of Childand Adolescent Psychiatry. 785
.....
LICAMELE AND GOLDBERG
,.,.~:: a stimulant. Thus, the literature on the use of of lithium for a variety of behavioral, conduct, and atypical affective illnesses in children is inconclusive. There are reports in the literature of the safe but equivocal use of psychostimulants and lithium in adults (Flemenbaum 1974; Van Kommer and Murphy, 1975; Anjust and Gershon, 1979; Bannet et al. 1980; Huey et aI., 1981). Brown et al. (1983) describe the treatment of an older adolescent with lithium and pemoline, but there is no literature on the concurrent use of lithium and a psychostimulant in earlier childhood disorders. Case Report
The patient is a white male who was first evaluated at age 6. At that time he presented with multiple problems including temper tantrums, attentional problems, hyperactivity, separation anxiety, emotional lability, nocturnal enuresis, binge eating of sweet and salty foods, hoarding food, lying, and stealing. On interview, the patient was noticeably clingy, clutching a blanket tightly while steadily sucking his thumb. He described frequent multiple fears and exhibited marked attentional problems and impulsivity. At times he appeared sad, but there were no signs of major depression such as crying or suicidal ideation, nor were there overt signs of psychosis. His intelligence seemed adequate and he was able to engage the interviewer. Developmental history revealed that the patient's prenatal course was marked by three uterine bleeds during his mother's pregnancy, slight placental separation, and, at partuition, his umbilical cord was wrapped around his neck. However, Apgar scores were high and the patient seemed to be in good health at birth. By history, the patient met developmental milestones on time and was a docile and cheerful child until about age 3, when he began exhibiting struggles about going to bed and eating. Later, his school and neighborhood behavior indicated severe problems in relating to peers. The patient was described as being quick to anger. His parents described him as "a long term discipline problem who is impulsive and cannot learn from mistakes." There was no evidence of physical or sexual abuse and none was reported. Family history revealed considerable marital strife. There was a significant incidence of clinical psychopathology in the nuclear and extended family. The patient's mother had a positive history for both depression and panic disorder which had responded to treatment with imipramine. Father had a history of depression, alcoholism, and obsessive/compulsive disorder. A younger sister was diagnosed as having separation anxiety disorder and phobias. A teenage cousin was diagnosed as either schizophrenic or bipolar affective disorder, and a maternal cousin was diagnosed as bipolar with a positive response to lithium. Medical history, physical and laboratory examinations, SMA-24 blood chemistries, CBC with platelet count and WBC differential, serum lead level, and thyroid studies were all within normal limits. The WISC-R indicated a Verbal IQ of 118, Performance IQ of 132, and an overall IQ of 128. Psychometric testing, including the Berry VMI, the Connors' Teacher Rating Scale (Connors, 1973), and the Bender-Gestalt test, yielded positive findings suggesting hyperactivity,
developmental delay, poor self-image, visual-motor perceptual impairments, and poor fine motor control. The medical and family history and the workup data led to the followingdiagnoses: attention deficit-hyperactive disorder, atypical conduct disorder, separation and phobic anxiety disorder, learning disability, and dysthymic disorder. Since there were no discrete episodes of mania or depression, the patient did not fulfill DSM-III criteria for bipolar disorder. Because the symptoms of ADD were so compelling, a regime of methylphenidate up to 20 mg t.i.d. was instituted. In addition, the patient was seen in individual psychotherapy. His mother was treated for depression with a positive response to psychotherapy and antidepressants, and both parents were taught behavioral management techniques. The combination of 20 mg of methylphenidate t.i.d. and other interventions produced noticeable improvement in the patient's ability to concentrate and attend to tasks, and his hyperactivity was markedly reduced. However, at age 7 he continued to manifest mood instability and a variety of conduct disturbances including anger, sadness, explosiveness,stealing, and lying. During that year, methylphenidate and the other interventions continued; however, his conduct disturbances exacerbated to the point where hospitalization was considered. A mental status examination performed at age 7 indicated the patient was alert, uncooperative, angry, denying of his problems, and blaming of others. There continued to be no indications of suicidal ideation, psychosis, or discrete manic episodes and the patient denied vegetative signs of depression. Research reports (Campbell et aI., 1984) on the use of lithium with children and the family's history of affective disorders with a positive response to lithium by relatives prompted a trial of lithium as an alternative to inpatient treatment. The parents opposed taking the patient off methylphenidate for a solo trial of lithium because of his history of becoming unmanageable after missing only one or two doses of methylphenidate. The unusualness of this medication regime and its possible side effects were fully explained and the parents signed a statement of informed consent. At age 7 lithium carbonate 300 mg b.i.d was instituted and achieved a blood level of between 0.7 and 0.9 meq/rnl when drawn 12 hours after the last dose. After about 10 days at that blood level the patient demonstrated such marked improvement in mood stability and conduct that the earlier consideration of inpatient treatment was abandoned. During the course of combined treatment (now totaling about 4 years), trials off of methylphenidate and lithium were attempted. Discontinuation of methylphenidate led to increased attentional difficulties, hyperactivity, and impulsivity within hours. A trial off lithium at age 9 led, within a week, to episodes of anger, irritability, sadness, and explosiveness. A Connors' Teacher Rating Scale (1973) done while the patient was off lithium produced results similar to scalesdone when the patient was on methylphenidate alone and on the combination oflithium and methylphenidate (Table I). The combination of methylphenidate and lithium did not cause any untoward side effects and was well tolerated by the patient. Height, weight, pulse, blood pressure, blood chemistries including creatinine and BUN, CBC, thyroid studies, and urinalysis have all remained within normal limits.
CONCURRENT USE OF LITHIUM AND METHYLPHENIDATE TABLE
I. Connors' Teacher Rating Scale
Medication Pre-methylphenidate, 10/83 Post-methylphenidate, 11/83 Methylphenidate, 1984 Methylphenidate with lithium,I/85 Methylphenidate with lithium, 1987 Methylphenidate without lithium, 1987
Hyperactivity Factor
Attentional Factor
16/18
6/6
2/18 4/18
0/6 3/6
4/18
3/6
4/18
3/6
3/18
3/6
Discussion In this case methylphenidate treatment, which was instituted because of the prominence of ADD, produced a marked diminution of attentional and hyperactive symptoms. The positive response of ADHD symptoms to methylphenidate has been well documented (Gittleman-Klein and Klein, 1987; Campbell and Spencer, 1988). Lithium was initiated to treat the residual mood instability and conduct disturbances (Campbell et al., 1984). This, too, resulted in improvement. Naturalistic on/off trials of each medication precipitated a return ofthe target symptoms. At this time, it remains unclear whether the patient has two disorders, two symptoms responsive to two different medications, or whether there is some interaction between the medications. Long-term follow-up will be needed to supply the answers. Prior studies on the concurrent use of methylphenidate (or d-amphetamine) and lithium in adult populations have been inconclusive (Flemenbaum, 1974; Van Kommer and Murphy, 1975; Anjust and Gershon, 1979; Bannet et aI., 1980; Huey et aI., 1981). In some cases lithium attenuated the psychostimulant and antidepressant effects of both medications. In other cases, either no effect or an augmentation effect was reported. In this young child, the combination oflithium and methylphenidate did not attenuate the therapeutic effects of either agent, nor was there any occurrence of untoward side effects. It is possible that methylphenidate and lithium have different neurobiologic loci of action in young children. Zametkin and Rapoport (1987) recently reviewed the neurobiology of ADD with hyperactivity (ADHD) and discussed the various hypotheses about its pathology and treatment. Although a larger pool of child patients might yield variable results (as with the adult cases), this case indicates that combined use of these agents can be effective in young children with ADD and a family history of affective disorders. As Munir et al. (1987) reported, there may exist a subgroup of patients with ADHD and conduct/oppositional disorders who have a higher rate of affective disorders when compared to ADHD patients without conduct/oppositional disorders. Well-controlled studies drawing upon larger juvenile patient populations with comorbid disorders are indicated. The present authors note that the coadministration of lithium and methylphenidate in this patient was necessitated by the parents' reluctance to stop methylphenidate and the need to attempt an intervention that might prevent hospitalization.
787
If one were to initiate such treatment, one should obtain informed consent, continually assess the effects of the medications, and monitor side effects, especially growth and renal and thyroid functions. In treating a developing child with combined medications it is vitally important to have periodic trials off each medication in order to continually assess the need for the use of both agents.
References Anjust, B. & Gershon, S. (1979), Variable attenuation of amphetamine effectsby lithium. Am. J. Psychiatry, 136:806-810. Bannet, J., Ebstein, P. R. & Belmiker, R. H. (1980), Clinical aspects of the interaction of lithium and stimulants. Br. J. Psychiatry, 136:204. Brown, R. P., Ingber, P. S. & Tross, S. (1983), Pemoline and lithium in a patient with attention deficit disorder. J. Clin. Psychiatry, 44:146-148. Campbell, M., Green, W. H. & Deutsch, S. I. (1985). Lithium carbonate. In: Child and Adolescent Psychopharmacology. Beverly Hills, CA: Sage Publications, pp. 115-131. - - Spencer, E. K. (1988), Psychopharmacology in child and adolescent psychiatry: a review of the past five years. J. Am. Acad. Child Adolesc. Psychiatry, 27:269-279.
- - Small, A. M. & Green, W. H. et at. (1984), Behavioral efficacy of haloperidol and lithium carbonate. Arch. Gen. Psychiatry, 41:650-656. Carlson, J. A. & Cantwell, D. P. (1979), A survey of depressive symptoms in a child and adolescent psychiatricpopulation. J. Am. Acad. Child Psychiatry, 18:587-599.
Connors, C. K. (1973), Rating scales for use in drug studies with children. Psychopharmacol. Bull., (Special issues) (DHEW Publication No. 73-9002):24-42. Delong, G. R. & Nieman, G. U. (1983), Lithium-induced behavior changes in children with symptoms suggesting manic-depressive illness. Psychopharmacol. Bull., 19:258-265. - - Aldershof, A. L. (1987), Long term experience with lithium treatment in childhood. J. Am. Acad. Child Adolesc. Psychiatry, 26:389-394. Dostal, T. (1972), Anti-aggressive effect of lithium salts in mentally retarded adolescents. In: Depressive States and Childhood and Adolescence, ed. A. L. Arnell. Stockholm: Almqvist and Wiskell. Dyson, W. L. & Barcal, A. (1970), Treatment of children oflithiumresponding parents. Current Therapeutic Research, 12:286-290. Flemenbaum, A. (1974), Does lithium block the effectsof amphetamine? Am. J. Psychiatry, 131 :820-821. Gastfriend, D. R., Biederman, J. & Jellinek, M. S. (1984), Desipramine in the treatment of adolescentswith attention deficitdisorder. Am. J. Psychiatry, 141:906-908.
Gittelman-Klein, R. & Klein, D. F. (1987), Pharmacotherapy of childhood hyperactivity. In: Psychopharmacology, The Third Generation ofProgress, ed. H. Y. Meltzer.New York: Raven Press,pp. 1215-1224. Greenhill, L., Rieder, R., Werda, P. et at. (1973), Lithium carbonate in the treatment of hyperactive children. Arch. Gen. Psychiatry, 28:636-640. Huey, L. Y., Janowsky, D. S., Judd, L. L. et at. (1981), Effects of lithium carbonate on methylphenidate induced mood, behavior and cognitiveprocesses. Psychopharmacology (Berlin), 73:161-164. Morrison, J. R. & Stewart, M. A. (1971), A family study of the hyperactive child syndrome. Bioi. Psychiatry, 3:189-195. Munir, K., Biederman,J. & Knee, D. (1987), Psychiatric co-morbidity in patients with attention deficit disorder. J. Am. Acad. Child Adolesc. Psychiatry, 26:844-848.
Robbins, L. N. (1966), Deviant Children Grown Up. Baltimore: Williams & Wilkins. Van Kommer, D. P. & Murphy, D.L. (1975), Attenuation of the euphoriant and activating effectsof I and I-amphetamine by lithium carbonate treatment. Psychopharmacologia, 44:215-24. Zametkin, A. J. & Rapoport, J. L. (1987), Neurobiology of attention deficit disorder with hyperactivity: where have we come in 50 years? J. Am. Acad. Child Adolesc. Psychiatry, 26:676-686.
•
The Concurrent Use of Lithium and Methylphenidate in a Child WILLIAM L. LICAMELE, M.D.,
AND
RICHARD L. GOLDBERG, M.D.
Abstract. The case of a young boy with symptoms of both attention deficit and affective disorders is presented. The patient was successfully treated witha combination of lithium and methylphenidate. Issues about comorbidity and polypharmacy in children are raised, and the concommitant useofIithium and methylphenidate in a childisdiscussed. 1. Am. Acad. Child Adolesc. Psychiatry, 1989, 28, 5:785-787. Key Words: methylphenidate, lithium, attention deficit disorder. Coadministration of two or more psychopharmacologic agents in children, as in adults, runs the risk of augmenting or attenuating either the therapeutic or the adverse effects of each agent. Polypharmacy is sometimes justified, however, when comorbid disorders occur. This is a common occurrence in childen in whom symptoms indicative of attention deficit disorder (ADD) coexist with affective symptomatology. Because the study ofcomorbidity and polypharmacy in juveniles is a relatively new field and there are few reported studies that offer guidance, clinicians must exercise caution, especially in areas where the possible side effects of polypharmacy on the developing child are uncertain. Given the special complexities in the treatment of childhood disorders, polypharmacy should be attempted only when the seriousness of the situation mandates such measures, e.g. to avoid hospitalization or to prevent self-injury. This paper describes the concurrent use of methylphenidate and lithium in a young child who manifests symptoms which might indicate the presence of comorbid disorders. Few studies have specifically addressed the question of whether affective disorders are primary or secondary to other disorders in children. Carlson and and Cantwell (1979) were among the first to distinguish primary vs. secondary affective disorders in juveniles. They found that 50% of all affective disorders were secondary and that 50% of these secondary disorders coexisted with "hyperactivity." Dyson and Barcal (1970) concluded that some children with early "hyperactivity" and a family history of bipolar disorder were actually manifesting early symptoms of bipolar disorder. These children were differentiated from hyperactive children in non bipolar families by a lack of soft signs and a failure to respond to stimulants. Family studies of hyperactive children (Morrison and Stewart, 1971) have not found a higher incidence of affective
disorders. However, in those studies, nonresponders to stimulants did have a higher incidence of affective disorders in their families. Robbins (1966), who studied long-term followup of hyperactive children, did not find a greater prevalence of adult bipolar disorders than would be expected in the general population. Lithium Treatment of Children and Adolescents Literature exists on the use oflithium for ADHD as well as for conduct or aggressive symptoms. Greenhill et al. (1973) used lithium in the treatment of severely hyperactive children who had not responded to stimulants and found either no effect or a worsening of target symptoms. Dostal (1972) treated severely disturbed, retarded, aggressive adolescents with lithium and reported that it alleviated anger, aggression, and hyperactivity. However, patients whose hyperkinetic behavior lacked an affective component did not show improvement. Delong and Nieman (1983), as summarized by Campbell et al. (1985), found that 16 children and adolescents who had previously had favorable responses to lithium responded positively in a double-blind discontinuation trial of lithium. Eleven of the 16 had been tested with stimulants for ADD on a prior occasion, and although the subjects benefited from lithium, the ADD symptoms did not improve. In a lithium trial with a sample of 196 children and adolescents, Delong and Aldershof (1987) reported that lithium was effective in 82% of subjects with emotionally unstable character disorder, 66% of subjects with bipolar affective disorder, and 71 % of children of lithium-responsive parents. Lithium was effective for ADD only in subjects with associated affective symptoms (38%), and in 11 of 19 such patients lithium worsened symptoms of ADD. On the other hand, Campbell (1984) reported a positive response to lithium in "hyper-aggressive children." In that double-blind study of 61 boys, both Haldol'" and Lithium" were found to equally decrease aggressiveand other conduct symptoms but Lithium had fewer side effects. Gastfriend et al. (1984) tried desipramine (an antidepressant and second line drug for ADD) with 12 adolescents with ADD who had not responded to stimulants. The authors reported that 11 of the 12 had a favorable response within a month. According to a table accompanying the report, one patient had a codiagnosis of depression and two were on lithium. The report did not explain why two patients were taking lithium
Accepted February 22. 1989. Dr. Licamele is Clinical Professor ofPsychiatry and Pediatrics and Director ofChild and Adolescent Psychiatric Services. and Dr. Goldberg is Acting Chairman. Department of Psychiatry, Georgetown University Hospital. Washington. D.C. Reprint requests to Dr. Licamele, Dept. of Psychiatry, Georgetown University Hospital, 3800 Reservoir Road. N. w.. Washington, DC 20007. 0890-8567/89/2805-0785$02.00/0© 1989 by the American Acad-
emy of Childand Adolescent Psychiatry. 785
.....
LICAMELE AND GOLDBERG
,.,.~:: a stimulant. Thus, the literature on the use of of lithium for a variety of behavioral, conduct, and atypical affective illnesses in children is inconclusive. There are reports in the literature of the safe but equivocal use of psychostimulants and lithium in adults (Flemenbaum 1974; Van Kommer and Murphy, 1975; Anjust and Gershon, 1979; Bannet et al. 1980; Huey et aI., 1981). Brown et al. (1983) describe the treatment of an older adolescent with lithium and pemoline, but there is no literature on the concurrent use of lithium and a psychostimulant in earlier childhood disorders. Case Report
The patient is a white male who was first evaluated at age 6. At that time he presented with multiple problems including temper tantrums, attentional problems, hyperactivity, separation anxiety, emotional lability, nocturnal enuresis, binge eating of sweet and salty foods, hoarding food, lying, and stealing. On interview, the patient was noticeably clingy, clutching a blanket tightly while steadily sucking his thumb. He described frequent multiple fears and exhibited marked attentional problems and impulsivity. At times he appeared sad, but there were no signs of major depression such as crying or suicidal ideation, nor were there overt signs of psychosis. His intelligence seemed adequate and he was able to engage the interviewer. Developmental history revealed that the patient's prenatal course was marked by three uterine bleeds during his mother's pregnancy, slight placental separation, and, at partuition, his umbilical cord was wrapped around his neck. However, Apgar scores were high and the patient seemed to be in good health at birth. By history, the patient met developmental milestones on time and was a docile and cheerful child until about age 3, when he began exhibiting struggles about going to bed and eating. Later, his school and neighborhood behavior indicated severe problems in relating to peers. The patient was described as being quick to anger. His parents described him as "a long term discipline problem who is impulsive and cannot learn from mistakes." There was no evidence of physical or sexual abuse and none was reported. Family history revealed considerable marital strife. There was a significant incidence of clinical psychopathology in the nuclear and extended family. The patient's mother had a positive history for both depression and panic disorder which had responded to treatment with imipramine. Father had a history of depression, alcoholism, and obsessive/compulsive disorder. A younger sister was diagnosed as having separation anxiety disorder and phobias. A teenage cousin was diagnosed as either schizophrenic or bipolar affective disorder, and a maternal cousin was diagnosed as bipolar with a positive response to lithium. Medical history, physical and laboratory examinations, SMA-24 blood chemistries, CBC with platelet count and WBC differential, serum lead level, and thyroid studies were all within normal limits. The WISC-R indicated a Verbal IQ of 118, Performance IQ of 132, and an overall IQ of 128. Psychometric testing, including the Berry VMI, the Connors' Teacher Rating Scale (Connors, 1973), and the Bender-Gestalt test, yielded positive findings suggesting hyperactivity,
developmental delay, poor self-image, visual-motor perceptual impairments, and poor fine motor control. The medical and family history and the workup data led to the followingdiagnoses: attention deficit-hyperactive disorder, atypical conduct disorder, separation and phobic anxiety disorder, learning disability, and dysthymic disorder. Since there were no discrete episodes of mania or depression, the patient did not fulfill DSM-III criteria for bipolar disorder. Because the symptoms of ADD were so compelling, a regime of methylphenidate up to 20 mg t.i.d. was instituted. In addition, the patient was seen in individual psychotherapy. His mother was treated for depression with a positive response to psychotherapy and antidepressants, and both parents were taught behavioral management techniques. The combination of 20 mg of methylphenidate t.i.d. and other interventions produced noticeable improvement in the patient's ability to concentrate and attend to tasks, and his hyperactivity was markedly reduced. However, at age 7 he continued to manifest mood instability and a variety of conduct disturbances including anger, sadness, explosiveness,stealing, and lying. During that year, methylphenidate and the other interventions continued; however, his conduct disturbances exacerbated to the point where hospitalization was considered. A mental status examination performed at age 7 indicated the patient was alert, uncooperative, angry, denying of his problems, and blaming of others. There continued to be no indications of suicidal ideation, psychosis, or discrete manic episodes and the patient denied vegetative signs of depression. Research reports (Campbell et aI., 1984) on the use of lithium with children and the family's history of affective disorders with a positive response to lithium by relatives prompted a trial of lithium as an alternative to inpatient treatment. The parents opposed taking the patient off methylphenidate for a solo trial of lithium because of his history of becoming unmanageable after missing only one or two doses of methylphenidate. The unusualness of this medication regime and its possible side effects were fully explained and the parents signed a statement of informed consent. At age 7 lithium carbonate 300 mg b.i.d was instituted and achieved a blood level of between 0.7 and 0.9 meq/rnl when drawn 12 hours after the last dose. After about 10 days at that blood level the patient demonstrated such marked improvement in mood stability and conduct that the earlier consideration of inpatient treatment was abandoned. During the course of combined treatment (now totaling about 4 years), trials off of methylphenidate and lithium were attempted. Discontinuation of methylphenidate led to increased attentional difficulties, hyperactivity, and impulsivity within hours. A trial off lithium at age 9 led, within a week, to episodes of anger, irritability, sadness, and explosiveness. A Connors' Teacher Rating Scale (1973) done while the patient was off lithium produced results similar to scalesdone when the patient was on methylphenidate alone and on the combination oflithium and methylphenidate (Table I). The combination of methylphenidate and lithium did not cause any untoward side effects and was well tolerated by the patient. Height, weight, pulse, blood pressure, blood chemistries including creatinine and BUN, CBC, thyroid studies, and urinalysis have all remained within normal limits.
CONCURRENT USE OF LITHIUM AND METHYLPHENIDATE TABLE
I. Connors' Teacher Rating Scale
Medication Pre-methylphenidate, 10/83 Post-methylphenidate, 11/83 Methylphenidate, 1984 Methylphenidate with lithium,I/85 Methylphenidate with lithium, 1987 Methylphenidate without lithium, 1987
Hyperactivity Factor
Attentional Factor
16/18
6/6
2/18 4/18
0/6 3/6
4/18
3/6
4/18
3/6
3/18
3/6
Discussion In this case methylphenidate treatment, which was instituted because of the prominence of ADD, produced a marked diminution of attentional and hyperactive symptoms. The positive response of ADHD symptoms to methylphenidate has been well documented (Gittleman-Klein and Klein, 1987; Campbell and Spencer, 1988). Lithium was initiated to treat the residual mood instability and conduct disturbances (Campbell et al., 1984). This, too, resulted in improvement. Naturalistic on/off trials of each medication precipitated a return ofthe target symptoms. At this time, it remains unclear whether the patient has two disorders, two symptoms responsive to two different medications, or whether there is some interaction between the medications. Long-term follow-up will be needed to supply the answers. Prior studies on the concurrent use of methylphenidate (or d-amphetamine) and lithium in adult populations have been inconclusive (Flemenbaum, 1974; Van Kommer and Murphy, 1975; Anjust and Gershon, 1979; Bannet et aI., 1980; Huey et aI., 1981). In some cases lithium attenuated the psychostimulant and antidepressant effects of both medications. In other cases, either no effect or an augmentation effect was reported. In this young child, the combination oflithium and methylphenidate did not attenuate the therapeutic effects of either agent, nor was there any occurrence of untoward side effects. It is possible that methylphenidate and lithium have different neurobiologic loci of action in young children. Zametkin and Rapoport (1987) recently reviewed the neurobiology of ADD with hyperactivity (ADHD) and discussed the various hypotheses about its pathology and treatment. Although a larger pool of child patients might yield variable results (as with the adult cases), this case indicates that combined use of these agents can be effective in young children with ADD and a family history of affective disorders. As Munir et al. (1987) reported, there may exist a subgroup of patients with ADHD and conduct/oppositional disorders who have a higher rate of affective disorders when compared to ADHD patients without conduct/oppositional disorders. Well-controlled studies drawing upon larger juvenile patient populations with comorbid disorders are indicated. The present authors note that the coadministration of lithium and methylphenidate in this patient was necessitated by the parents' reluctance to stop methylphenidate and the need to attempt an intervention that might prevent hospitalization.
787
If one were to initiate such treatment, one should obtain informed consent, continually assess the effects of the medications, and monitor side effects, especially growth and renal and thyroid functions. In treating a developing child with combined medications it is vitally important to have periodic trials off each medication in order to continually assess the need for the use of both agents.
References Anjust, B. & Gershon, S. (1979), Variable attenuation of amphetamine effectsby lithium. Am. J. Psychiatry, 136:806-810. Bannet, J., Ebstein, P. R. & Belmiker, R. H. (1980), Clinical aspects of the interaction of lithium and stimulants. Br. J. Psychiatry, 136:204. Brown, R. P., Ingber, P. S. & Tross, S. (1983), Pemoline and lithium in a patient with attention deficit disorder. J. Clin. Psychiatry, 44:146-148. Campbell, M., Green, W. H. & Deutsch, S. I. (1985). Lithium carbonate. In: Child and Adolescent Psychopharmacology. Beverly Hills, CA: Sage Publications, pp. 115-131. - - Spencer, E. K. (1988), Psychopharmacology in child and adolescent psychiatry: a review of the past five years. J. Am. Acad. Child Adolesc. Psychiatry, 27:269-279.
- - Small, A. M. & Green, W. H. et at. (1984), Behavioral efficacy of haloperidol and lithium carbonate. Arch. Gen. Psychiatry, 41:650-656. Carlson, J. A. & Cantwell, D. P. (1979), A survey of depressive symptoms in a child and adolescent psychiatricpopulation. J. Am. Acad. Child Psychiatry, 18:587-599.
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