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24-06-2007, 11:26
Atypical Antipsychotics are not safer. But they sure do make a lot more money, don't they?
Side Effects of Atypical Antipsychotics in Children and Adolescents
Roger Z. Samuel, MD
Dear Editor:
Atypical antipsychotics are increasingly being used in children and adolescents1 for a variety of psychiatric conditions, mainly off label. As such, I would like to share three cases of potentially serious side effects that occurred as a result of atypical antipsychotic treatment of psychiatric conditions.
Conditions for which atypical antipsychotics are prescribed include bipolar disorder, psychotic depression, schizophrenia, pervasive developmental disorders, attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder. They are also used symptomatically to treat rage, insomnia, and anorexia (sometimes iatrogenic in origin).
While considered safer in short and long-term use compared to older, typical antipsychotics,1 they are not free of adverse effects. Their use in larger numbers of youths suggests the need to clarify the actual incidence of serious adverse events.
Atypical antipsychotics share many of the side effects of typical antipsychotics, including sedation, akathisia, weight gain, extrapyramidal symptoms (EPS), neuromalignant syndrome, and tardive dyskinesia2,3; longer experience with them have shown that new risks need to be considered, such as metabolic syndromes and QTc prolongation. The incidence of these risks in youths cannot be easily predicted due to the paucity of long-term studies in this population. Younger patients appear to be at a higher risk of developing EPS. Although atypical antipsychotics may be associated with a lower incidence of EPS in youth, a rapid dose escalation is associated with higher risk of EPS as is the use of higher doses.3
Case Report:
This report describes the occurrence of three potentially serious side effects in two children and one adolescent who were prescribed atypical antipsychotics for psychiatric conditions.
The first case revealed withdrawal dyskinesia in a 7-year-old, Hispanic female who was in treatment for ADHD, ODD, and mild obsessive-compulsive disorder. In addition, bipolar disorder was suspected. She was tried on a number of medications alone and in combination including antidepressants (venlafaxine, mirtazapine, sertraline), stimulants (pemoline, amphetamine salts), α-agonists (clonidine, guanfacine), and thymoleptics (lithium, carbamazepine). Before risperidone was discontinued, after a 1-month trial and the occurrence of side effects, including EPS, she was also tried on 0.5 mg/day and titrated up to 1.5 mg/day. After 3 days, she was started on olanzapine 2.5 mg/day in combination with carbamazepine, sertraline, and amphetamine salts. The olanzapine was titrated up to a total daily dose of 15 mg. After a year, she was on olanzapine 7.5 mg/day, whereupon she required inpatient admission. The admitting psychiatrist abruptly discontinued the olanzapine because he disagreed with the diagnosis of bipolar disorder. Two days after discharge from the inpatient unit, at outpatient follow up, the patient was noted to have tongue, finger, and lower extremity dyskinesia. Her mother reported that she was also rubbing both sides of her face with her hands. One month later, these movements had markedly decreased and 2 months later they completely resolved.
The second case was of torticollis in a 13-year-old white male diagnosed with ADHD, bipolar disorder, and ODD. He had been on multiple medications and combinations since childhood, including stimulants, thymoleptics, gabapentin, α-adrenergic agonists, tricyclic antidepressants, donepezil, modafinil, galantamine, selective serotonin reuptake inhibitors, buspirone, and neuroleptics. He ended up in a somewhat stable state on a combination of methylphenidate extended release 60 mg QAM, buspirone 15 mg BID, atomoxetine 60 mg BID, and quetiapine 200 mg Q4PM, 600 mg QHS. The patient complained of morning somnolence and was angry about having to fall asleep earlier than he wanted because of nighttime sedation caused by quetiapine. At his and his mother’s request, quetiapine was tapered down to 200 mg BID and aripiprazole 10 mg QPM was added (to prevent decompensation). He developed side effects on a trip out of town, after physical exertion. He had “muscle spasms,” including torticollis, even after fluids were replenished. The dystonic reactions responded to diphenhydramine hydrochloride 25 mg BID, reduction of aripiprazole to 5 mg QPM, and quetiapine to 200 mg QD. They completely resolved on quetiapine 300 mg QHS (increased because of manic symptoms), aripiprazole 5 mg QPM, and benztropine 0.5 mg BID. An attempt to wean the patient off neuroleptics failed and he ended up back on quetiapine 300 mg QHS and off aripiprazole 1 month later. The EPS did not recur even when he was taken off benztropine.
The third case was of a 3.5-year-old white male who was diagnosed by his previous psychiatrist to have bipolar disorder and ADHD, for which he was prescribed olanzapine 2.5 mg QAM in outpatient treatment. Olanzapine was increased to 2.5 mg BID with salutary results. Approximately 6 months later, the child developed priapism for which he was seen at the local hospital emergency room. He was not taking any other medication at the time other than a prednisone nebulizer PRN for seasonal asthma. The emergency room physician attributed the priapism to olanzapine, whereupon the olanzapine was discontinued. Within a few hours, the priapism resolved. At follow up 3 weeks later, the psychiatrist put the child back on olanzapine 2.5 mg BID and the priapism did not recur.
The prevalence of neuroleptic-induced tardive dyskinesia and withdrawal dyskinesia in children and adolescents has been reported to range between 0% and 51%.2 These cases should serve to alert clinicians to the potential serious side effects of atypical antipsychotics, which are being increasingly utilized in children and in adolescents for a variety of clinical conditions. Though available data suggest that target doses of antipsychotics are similar in adolescents and adults with psychotic disorders, children with psychosis and adolescents with other conditions generally achieve optimal benefit from lower doses. The principle of “start low and go slow” definitely applies to the initiation of antipsychotics in youths.3
Sincerely,
— Roger Z. Samuel, MD
References
1. Correll C, Leucht S, Kane J. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. Am J Psychiatry. 2004;161(3):414-425.
2. Green WH. Child and Adolescent Clinical Psychopharmacology, third ed. Phildelphia, PA: Lippincot Williams & Wilkins; 2001.
3. Martin A. Pediatric Psychopharmacology. New York, NY: Oxford University Press; 2003.
Dr. Samuel is president and medical director of the Boca Raton Psychiatric Group in Florida.
Side Effects of Atypical Antipsychotics in Children and Adolescents
Roger Z. Samuel, MD
Dear Editor:
Atypical antipsychotics are increasingly being used in children and adolescents1 for a variety of psychiatric conditions, mainly off label. As such, I would like to share three cases of potentially serious side effects that occurred as a result of atypical antipsychotic treatment of psychiatric conditions.
Conditions for which atypical antipsychotics are prescribed include bipolar disorder, psychotic depression, schizophrenia, pervasive developmental disorders, attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder. They are also used symptomatically to treat rage, insomnia, and anorexia (sometimes iatrogenic in origin).
While considered safer in short and long-term use compared to older, typical antipsychotics,1 they are not free of adverse effects. Their use in larger numbers of youths suggests the need to clarify the actual incidence of serious adverse events.
Atypical antipsychotics share many of the side effects of typical antipsychotics, including sedation, akathisia, weight gain, extrapyramidal symptoms (EPS), neuromalignant syndrome, and tardive dyskinesia2,3; longer experience with them have shown that new risks need to be considered, such as metabolic syndromes and QTc prolongation. The incidence of these risks in youths cannot be easily predicted due to the paucity of long-term studies in this population. Younger patients appear to be at a higher risk of developing EPS. Although atypical antipsychotics may be associated with a lower incidence of EPS in youth, a rapid dose escalation is associated with higher risk of EPS as is the use of higher doses.3
Case Report:
This report describes the occurrence of three potentially serious side effects in two children and one adolescent who were prescribed atypical antipsychotics for psychiatric conditions.
The first case revealed withdrawal dyskinesia in a 7-year-old, Hispanic female who was in treatment for ADHD, ODD, and mild obsessive-compulsive disorder. In addition, bipolar disorder was suspected. She was tried on a number of medications alone and in combination including antidepressants (venlafaxine, mirtazapine, sertraline), stimulants (pemoline, amphetamine salts), α-agonists (clonidine, guanfacine), and thymoleptics (lithium, carbamazepine). Before risperidone was discontinued, after a 1-month trial and the occurrence of side effects, including EPS, she was also tried on 0.5 mg/day and titrated up to 1.5 mg/day. After 3 days, she was started on olanzapine 2.5 mg/day in combination with carbamazepine, sertraline, and amphetamine salts. The olanzapine was titrated up to a total daily dose of 15 mg. After a year, she was on olanzapine 7.5 mg/day, whereupon she required inpatient admission. The admitting psychiatrist abruptly discontinued the olanzapine because he disagreed with the diagnosis of bipolar disorder. Two days after discharge from the inpatient unit, at outpatient follow up, the patient was noted to have tongue, finger, and lower extremity dyskinesia. Her mother reported that she was also rubbing both sides of her face with her hands. One month later, these movements had markedly decreased and 2 months later they completely resolved.
The second case was of torticollis in a 13-year-old white male diagnosed with ADHD, bipolar disorder, and ODD. He had been on multiple medications and combinations since childhood, including stimulants, thymoleptics, gabapentin, α-adrenergic agonists, tricyclic antidepressants, donepezil, modafinil, galantamine, selective serotonin reuptake inhibitors, buspirone, and neuroleptics. He ended up in a somewhat stable state on a combination of methylphenidate extended release 60 mg QAM, buspirone 15 mg BID, atomoxetine 60 mg BID, and quetiapine 200 mg Q4PM, 600 mg QHS. The patient complained of morning somnolence and was angry about having to fall asleep earlier than he wanted because of nighttime sedation caused by quetiapine. At his and his mother’s request, quetiapine was tapered down to 200 mg BID and aripiprazole 10 mg QPM was added (to prevent decompensation). He developed side effects on a trip out of town, after physical exertion. He had “muscle spasms,” including torticollis, even after fluids were replenished. The dystonic reactions responded to diphenhydramine hydrochloride 25 mg BID, reduction of aripiprazole to 5 mg QPM, and quetiapine to 200 mg QD. They completely resolved on quetiapine 300 mg QHS (increased because of manic symptoms), aripiprazole 5 mg QPM, and benztropine 0.5 mg BID. An attempt to wean the patient off neuroleptics failed and he ended up back on quetiapine 300 mg QHS and off aripiprazole 1 month later. The EPS did not recur even when he was taken off benztropine.
The third case was of a 3.5-year-old white male who was diagnosed by his previous psychiatrist to have bipolar disorder and ADHD, for which he was prescribed olanzapine 2.5 mg QAM in outpatient treatment. Olanzapine was increased to 2.5 mg BID with salutary results. Approximately 6 months later, the child developed priapism for which he was seen at the local hospital emergency room. He was not taking any other medication at the time other than a prednisone nebulizer PRN for seasonal asthma. The emergency room physician attributed the priapism to olanzapine, whereupon the olanzapine was discontinued. Within a few hours, the priapism resolved. At follow up 3 weeks later, the psychiatrist put the child back on olanzapine 2.5 mg BID and the priapism did not recur.
The prevalence of neuroleptic-induced tardive dyskinesia and withdrawal dyskinesia in children and adolescents has been reported to range between 0% and 51%.2 These cases should serve to alert clinicians to the potential serious side effects of atypical antipsychotics, which are being increasingly utilized in children and in adolescents for a variety of clinical conditions. Though available data suggest that target doses of antipsychotics are similar in adolescents and adults with psychotic disorders, children with psychosis and adolescents with other conditions generally achieve optimal benefit from lower doses. The principle of “start low and go slow” definitely applies to the initiation of antipsychotics in youths.3
Sincerely,
— Roger Z. Samuel, MD
References
1. Correll C, Leucht S, Kane J. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. Am J Psychiatry. 2004;161(3):414-425.
2. Green WH. Child and Adolescent Clinical Psychopharmacology, third ed. Phildelphia, PA: Lippincot Williams & Wilkins; 2001.
3. Martin A. Pediatric Psychopharmacology. New York, NY: Oxford University Press; 2003.
Dr. Samuel is president and medical director of the Boca Raton Psychiatric Group in Florida.