Kaplan + Sadock's Synopsis of Psychiatry, 11e

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31.12b Early-Onset Bipolar Disorder

Psychosocial Treatment Psychosocial treatment interventions for early onset bipolar ill- ness have included a family-focused treatment. This treatment consists of several sessions of psychoeducation, then sessions focusing on current stressors and mood management plan, and then several sessions of communication enhancement train- ing and problem-solving skills training. The use of this type of intervention for youth diagnosed with bipolar disorder as well as youth at risk for the disorder by virtue of their family history or subthreshold conditions has been of value. Adjunc- tive family-focused psychoeducational treatment modified for children and adolescents has been shown to reduce relapse rate. Children and adolescents treated with mood-stabilizing agents in addition to a psychosocial intervention showed improvement in depressive symptoms, manic symptoms, and behavioral dis- turbance over 1 year. A year-long trial of a modified Family Focused Treatment- High Risk in youth with bipolar disorder showed significant improvement in mood disturbance, especially depressive mood and hypomania, and improved psychosocial functioning. Fam- ily-focused treatment for high-risk youth is a promising inter- vention that deserves further investigation as a longitudinal follow-up to determine the course of youth at risk to develop bipolar disorder. R eferences Axelson DA, Birmaher B, Strober M, Goldstein BI, Ha W, Gill MK, Goldstein TR, Yen S, Hower H, Hunt JI, Liao F, Iyengar S, Dickstein D, Kim E, Ryan ND, Frankel E, Keller MB. Course of subthreshold bipolar disorder in youth: Diag- nostic progression from bipolar disorder not otherwise specified. J Am Acad Child Adolesc Psychiatry. 2011;50:1001–1016. Carlson GA. Bipolar disorder and mood dysregulation. Proceedings; AACAP 2011 Psychopharmacology Update Institute: Controversies in child and ado- lescent psychopharmacology. 2011;257–284. Carlson GA, Myer SE. Early-onset bipolar disorder In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9 th ed. Vol. 2. Lippincott Williams & Wilkins; 2009:3663. Correll CU, Sheridan EM, DelBello MP. Antipsychotic and mood stabilizer effi- cacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials. Bipolar Disorders. 2010;12:116–141. Correll CU, Kratochvil CJ, March JS. Developments in pediatric psychopharma- cology: Focus on stimulants, antidepressants and antipsychotics. J Clin Psy- chiatry. 2011;72:655–670. Findling RL, Landersdorfer CB, Kafantaris V, Pavulari M, McNamara NK, McClellan J, Frazier JA, Sikich L, Kowatch R, Lingler J, Faber J, Taylor-Zapata, Jusko WJ. First-dose pharmacokinetics of lithium carbonate in children and adolescents. J Clin Psychopharmacol. 2010;30:404–410. Larsky T, Krieger A, Elixhauser A, Vitiello B. Children’s hospitalizations with a mood disorder diagnosis in general hospitals in the United States 2000-2006. Child Adolesc Psychiatry Mental Health. 2011;5:27–34. Mathieu F, Dizier M-H, Etain B, Jamain S, Rietschel M, Maier W, Albus M, McKeon P, Roche S, Blackwood D, Muir W, Henry C, Malafosse A, Preisig M, Ferrero F, Cichon S, Schumacher J, Ohlraun S, Propping P, Jamra RA, Schulze TG, Zelenica D, Charon C, Marusic A, Dernovsek MC, Gurling H, Nothen M, Lathrop M, Leboyer M, Bellivier F. European collaborative study of early-onset bipolar disorder: Evidence for heterogeneity on 2q14 according to age at onset. Am J Med Genet Part B. 2010;153B:1425–1433. McNamara RK, Nandagopal JJ, Strakowski SM, DelBello M. Preventive strat- egies for early-onset bipolar disorder. Toward a clinical staging model. CNS Drugs. 2010; 24:983-996. Miklowitz DJ, Chang KD, Taylor DO, George EL, Singh MK, Schneck CD, Dick- inson LM, Howe ME, Garber J. Early psychosocial intervention for youth at risk for bipolar I or II disorder: A one-year treatment development trial. Bipolar Disorders. 2011;13:67–75. Moreno C, Laje G, Blancvo C, Jiang H, Schmidtg AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007;64:1032–1039. Nieto RG, Castellanos FX. A meta-analysis of neuropsychological functioning in patients with early onset schizophrenia and pediatric bipolar illness. J Clin Child Adolesc Psychol. 2011;40:266–280.

a greater likelihood is seen of mixed states and rapid cycling, and higher rates of polarity changes compared with those who develop bipolar disorders in late adolescence or early adulthood. Treatment Treatment of early onset bipolar disorder incorporates multi- modal interventions including pharmacotherapy, psychoeduca- tion, psychosocial intervention with the family and the child, and school interventions to optimize a child’s school adjustment and achievement. Pharmacotherapy Two classes of medications—atypical antipsychotics and mood stabilizing agents—are the most well-studied agents that pro- vide efficacy in the treatment of early-onset bipolar disorders. Eight randomized controlled trials have shown efficacy of atypi- cal antipsychotic agents in the treatment of bipolar disorder in youth between the ages of 10 and 17 years. These studies compared an atypical antipsychotic to placebo, or compared an atypical antipsychotic to a mood stabilizer, or added an anti- psychotic to a mood-stabilizing agent. The atypical antipsychot- ics included olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone. All five of the atypical antipsychotic stud- ies demonstrated significant efficacy in the treatment of early onset bipolar manic or mixed states. A recent trial comparing quetiapine and valproate found that both were efficacious, but the quetiapine was superior in the speed of its effect. In another trial comparing risperidone and divalproex treatment for bipolar disorder in youth, risperidone was found to have a more rapid improvement and a greater final reduction in manic symptoms compared to divalproex. Mood-stabilizing agents have been used in open trials and anecdotally with early onset bipolar illness with little evidence of efficacy at this time. In trials using lithium or divalproex for treat- ment of early onset bipolar disorder, responses were less robust compared to results with atypical antipsychotics. Controlled trials have provided some evidence suggesting that lithium is efficacious in the management of aggression behavior disorders. Although lithium has been approved for use in adolescent mania, more research is needed to know if lithium is effective for more classic forms of mania in adolescents. The Collaborative Lith- ium Trials (CoLT) established a set of protocols to establish the safety and potential efficacy of lithium in youth, and to develop studies to provide evidence-based dosing of lithium for youth. A group of researchers recently studied the first-dose pharma- cokinetics of lithium carbonate in youth and found that clear- ance and volume are correlated with total body weight in youth, and particularly with fat-free mass. Difference in body size was consistent with the pharmacokinetics of lithium metabolism in children and adults. An open-label trial of lamotrigine (Lamictal) in the treatment of bipolar depression among youth provides pos- sible support for its use in children and adolescents. Current evidence suggests a faster response and more robust effect with atypical antipsychotics compared to mood-stabiliz- ing agents in the treatment of early-onset bipolar disorder. How- ever, given the severity and impairment of bipolar disorder in youth, when only partial recovery is achieved, consideration of adding an additional agent may be necessary.