Case report: Multiple diagnoses and drugs
JM, age 12, presented with his mother to address symptoms of hyperactivity and impulsive aggression. The boy also complained that his medications made him fall asleep during the day.
He is receiving five medications: a long-acting stimulant, atypical antipsychotic, anticonvulsant, alpha agonist, and selective serotonin reuptake inhibitor (SSRI). He had received numerous other medications, but prescription records are unavailable or incomplete.
Diagnostic history. Since age 5, JM has been diagnosed as having attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, bipolar disorder, major depressive disorder, and learning disorders. On examination, the boy met DSM-IV criteria for ADHD, learning disorders, and conduct disorder (Table 2). He has a history of starting fights with peers, bullying, destroying property, lying, and stealing from stores and peers.
His mother stated that her son had always had irritable and labile periods, especially when he did not get his way. She was told during a previous psychiatric evaluation that the boy’s "mood swings" indicated bipolar disorder. On examination, however, he had no other bipolar symptoms, and his condition was chronic, not cyclic.
JM typically cries when he does not get his way, his mother reported, but he has no history of sleep or appetite changes that could suggest depression. He is happy when he can do as he pleases.
Reducing medications. After reviewing JM’s medications and performing the psychiatric assessment, the psychiatrist developed a plan to maximize his psychosocial and educational treatments and alter his medications and dosages. The first step was to increase the stimulant dosage to determine whether JM would be less hyperactive and impulsively aggressive.
The psychiatrist was concerned that the anticonvulsant, alpha agonist, and SSRI were not helping and could cause adverse events. He discussed slowly weaning these drugs one at a time with JM and his mother, and they agreed. The goal was to manage JM over time and to reduce his medications to one (ideally) or two (if necessary), possibly continuing the atypical antipsychotic.
Risperidone also reduced aggression in children with normal intelligence in one small study.7 As a cautionary note, however, long-term risperidone treatment has been associated with withdrawal dyskinesias.8
Olanzapine, quetiapine, ziprasidone, and aripiprazole are less well-studied for treating pediatric aggression but are preferable to conventional agents when antipsychotics are considered.
Recommendation. Expert consensus opinion2 recommends using atypicals when psychosocial treatments and first-line medications for primary conditions have failed. Start with low dosages, and titrate up slowly while monitoring symptoms and side effects. Because no studies have compared any atypical’s efficacy over others for aggressive behavior, base your choices on:
- discussions with the patient and family (Box 1)
- medical comorbidities
- how the patient responded to antipsychotics in the past
- side-effect profile
- long-term treatment planning.2
If the patient cannot tolerate the medication or does not respond after 4 to 6 weeks, try switching atypicals. To improve partial response, consider adding a mood stabilizer such as lithium or divalproex. If aggressive symptoms remit for 6 months or longer, attempt to taper or discontinue the antipsychotic.2
Lithium
In placebo-controlled trials, lithium reduced aggression in:
- male prisoners ages 16 to 24.9
- children ages 7 and 12 with conduct disorder10
- children and adolescents ages 10 to 17 with conduct disorder.11
Among these studies, only ours11 specifically measured aggression. We randomly assigned 40 children to receive 4 weeks of lithium, 900 to 2,100 mg/d (mean 1,425 ± 321 mg/d), or placebo. Serum lithium levels were 0.78 to 1.55 mEq/L (mean 1.07 ± 0.19 mEq/L). We used the Overt Aggression Scale (OAS)12,13 (see Related resources) to track frequency and severity of verbal aggression, aggression against objects, aggression against others, and self-aggression.
Lithium reduced aggression more than did placebo, as measured by the clinician-rated Clinical Global Impressions (CGI) scale and staff-rated Global Clinical Judgments (Consensus) Scale (GCJCS). The CGI showed a 70% response rate with lithium and 20% with placebo. Similarly, the GCJCS scale showed 80% response with lithium and 30% with placebo.
The aggression reduction with lithium was statistically significant and clinically evident. Most subjects (37 of 40) experienced at least one adverse event, however, whether receiving lithium or placebo. Nausea, vomiting, and urinary frequency were significantly more common in the lithium-treated group than with placebo. Fewer adverse events were reported in a similar outpatient study,14 probably because of less-frequent monitoring.
Lithium did not reduce aggression in adolescent girls treated for 2 weeks15 or in an outpatient study of children with ADHD.16
Recommendation. Lithium has shown efficacy for reducing severe aggression in hospitalized children with conduct disorder but not in similar outpatients. Consider this drug to reduce severe aggression in children with conduct disorder, especially if they have failed other treatments.