Evidence-Based Treatment of Pediatric Bipolar Disorder

In the past few years, we’ve seen a growing body of scientific evidence that supports the efficacy of mood stabilizers and atypical antipsychotics to treat young patients with bipolar disorder. Lithium, olanzapine, aripiprazole, and risperidone monotherapy are FDA-approved for manic or mixed states in pediatric patients, while quetiapine is approved as monotherapy or as an adjunct to lithium or divalproex for manic states.

We’ve also learned more about the safety and tolerability of approved medications in this population. Lithium is generally well tolerated in children and adolescents, but does have the potential to cause thyroid and renal dysfunction and can be toxic in overdose¹; blood monitoring is therefore essential when using lithium. Atypical antipsychotics can also have adverse effects, and children and adolescents appear to be at a higher risk for these than adults.² Somnolence is one of the most common side effects; others include sedation, weight gain, negative metabolic effects, prolactin elevation, and EPS. However, side effect profiles do differ within the class: olanzapine has the greatest association with weight gain and adverse metabolic effects, while aripiprazole has the least. When prescribing an atypical, obtain baseline metabolic measures and regularly monitor your young patients.

Other medications have been studied for pediatric bipolar disorder, but, so far, the results are mixed. For instance, divalproex may³ or may not⁴ be more effective than placebo for treating mania. The anticonvulsant oxcarbazepine⁵ didn’t show a significant benefit for mania or mixed symptoms compared with placebo, and topiramate⁶ had inconclusive evidence. An open-label study⁷ found lamotrigine to be effective as monotherapy or as adjunctive treatment in pediatric bipolar depression, and preliminary findings suggest clozapine may benefit pediatric patients with treatment-resistant manic or mixed episodes.⁸

Obviously, more comparative and placebo-controlled studies are needed for these and other medications. New research on the safety and efficacy of combination therapies to treat children and adolescents with bipolar disorder could really help clinicians, young patients, and their families make evidence-based decisions. But, effective and generally well-tolerated medications are available to treat these young patients that can, when combined with psychosocial approaches that focus on academic, social, and family functioning, relieve some of the burden associated with this complex and potentially devastating illness.

Financial Disclosure:Dr Findling, in the past 12 months, has received research support from AstraZeneca, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Johnson & Johnson, Eli Lilly, Merck, Otsuka, Pfizer, Rhodes, Shire, Supernus, and Wyeth; has served as a consultant to Alexza, Bristol-Myers Squibb, Forest, GlaxoSmithKline, KemPharm, Eli Lilly, Lundbeck, Merck, Novartis, Noven, Otsuka, Pfizer, Schering-Plough, Seaside Therapeutics, Sepracor, Shire, Sunovion, Supernus, and Transcept; and has served as a speaker for Shire.

Abbreviations: EPS = extrapyramidal symptoms, FDA = US Food and Drug Administration

REFERENCES

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2. Correll CU. Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. J Clin Psychiatry. 2008;69(suppl 4):26–36.

3. Kowatch RA, Findling RL, Scheffer RE, et al. Pediatric bipolar collaborative mood stabilizer trial. Poster presented at: 54th annual meeting of the American Academy of Child and Adolescent Psychiatry (AACAP); October 23–28, 2007; Boston, MA.

4. Wagner KD, Redden L, Kowatch RA, et al. A double-blind, randomized, placebo-controlled trial of divalproex extended-release in the treatment of bipolar disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2009;48(5):519–532.

5. Wagner KD, Kowatch RA, Emslie GJ, et al. A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents [published correction appears in Am J Psychiatry. 2006;163(10):1843]. Am J Psychiatry. 2006;163(7):1179–1186.

6. DelBello MP, Findling RL, Kushner S, et al. A pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2005;44(6):539–547.

7. Chang K, Saxena K, Howe M. An open-label study of lamotrigine adjunct or monotherapy for the treatment of adolescents with bipolar depression. J Am Acad Child Adolesc Psychiatry. 2006;45(3):298–304.

8. Masi G, Mucci M, Millepiedi S. Clozapine in adolescent inpatients with acute mania. J Child Adolesc Psychopharmacol. 2002;12(2):93–99.​