The Challenges of Treating Youths With Bipolar Disorder

Bipolar disorder (BD) is recognized as a serious disorder. It has an adverse impact on many areas of a child’s development-including cognitive, emotional, and social functioning. Children with BD are at significant risk for substance use and suicidality. Further identification of effective treatments is a pressing public health concern.

At the same time, there is substantial controversy about the use of psychotropic medications in youth, especially in children, with BD. The widespread use of atypical antipsychotics in this age-group is of particular concern, given their cardiometabolic risks. Yet, to date, atypical anti-psychotics have the largest evidence base for their efficacy in the treatment of youths with bipolar I disorder, manic or mixed.

Three atypical antipsychotics-aripiprazole, quetiapine, and risperidone-have FDA approval for the treatment of 10- to 17-year-olds with bipolar I disorder, manic or mixed. Olanzapine has FDA approval that is limited to youths aged 13 to 17 years with bipolar I disorder. The only other medication option available for clinicians who prefer to use an FDA-approved agent is lithium for those 12 to 17 years old.

Ongoing challenges

• FDA-approved medications. There are a limited number of FDA-approved medications for youths with BD. Moreover, there are no FDA-approved medications for children younger than 10 years, despite an earlier age at onset of this illness in many children. Many clinicians and parents do not want to wait until a child’s 10th birthday to start treating the disorder. By default, clinicians usually prescribe medications that have demonstrated efficacy in older children in the absence of any information about their efficacy in younger children with BD.

• Few long-term studies. Evidence for the efficacy and safety of atypical antipsychotics in the treatment of youths with BD is based on acute treatment studies of 3 to 4 weeks’ duration. There is a glaring paucity of data about the long-term efficacy and safety of these medications in youth. Current bipolar treatment guidelines recommend treatment for at least 12 to 24 months after sustained remission of symptoms.

• Anticonvulsants. Published studies of anticonvulsants-including divalproex extended-release,¹ oxcarbazepine,² and topiramate³-have not demonstrated their superiority to placebo in the treatment of youths with bipolar I disorder. These agents have a warning in the prescribing label related to increased risk of suicidal thoughts and behaviors.

• Adjunct therapy. The atypical antipsychotics-aripiprazole and quetiapine-have FDA approval as an adjunct to treatment with lithium or valproate for children older than 10 years who have bipolar I disorder. However, valproate does not have FDA approval for use in children and adolescents with bipolar I disorder.

• Weight gain. Significant weight gain has been associated with the use of atypical antipsychotics in children and adolescents. In a 12-week study of atypical antipsychotic medication use in youths, mean weight gain was 8.5 kg with olanzapine, 6.1 kg with quetiapine, 5.3 kg with risperidone, and 4.4 kg with aripiprazole.⁴ These figures compare with a 0.2-kg weight gain for an unmedicated control group.

In addition, there were significant increases in mean levels of total cholesterol, triglycerides, and non–high-density lipoprotein (HDL) cholesterol and in the ratio of triglycerides to HDL cholesterol with olanzapine and quetiapine. Triglyceride levels increased significantly with risperidone. No significant changes in metabolic parameters were found in the aripiprazole-treated group compared with the untreated group.

• Psychotherapy. The efficacy of psychotherapy is being examined as adjunctive treatment rather than as monotherapy. Therefore, it is unlikely there will be an evidence base to support psychotherapy as the major component of treatment of youths with BD.

Suggestions for clinicians

• Full discussion. As part of the informed consent process, discuss with parents (as well as with adolescents) the limitations of the evidence base regarding both efficacy and safety of medications in treating symptoms of BD. Inform parents that there are minimal data about the long-term effects of these medications.

• Adverse event monitoring. Carefully monitor for evidence of adverse medication effects. A schedule for monitoring youths treated with atypical antipsychotics has been published, which clinicians may find useful.⁵

• Monitoring weight. Include weight management in your treatment plan and educate patients and parents about ways to minimize weight gain. Specific strategies to prevent and manage weight gain in this setting have been developed.⁶ A 12-item list related to eating and exercise may be helpful for patients and parents alike.⁶

• Additional treatment components. Inform parents about psychoeducation, therapy, and/or support groups to supplement medication treatment.

Despite the current limitations regarding medications, there has been a remarkable increase in the evidence base regarding treatment of BD in youths in the past 5 years. Studies are needed that compare different classes of medications, examine the safety of long-term medication use, determine the efficacy of medications in young children, and assess the effectiveness of medication combinations.

References:

References

1. 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;48:519-532.
2. 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;163:1843]. Am J Psychiatry. 2006;163:1179-1186.
3. 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;44:539-547.
4. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents [published correction appears in JAMA. 2009;302:2322]. JAMA. 2009;302: 1765-1773.
5. Correll CU. Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes. J Am Acad Child Adolesc Psychiatry. 2008;47:9-20.
6. Correll CU, Carlson HE. Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2006;45:771-791.