A Pharmacologic Algorithm for Youth Who Are at High Risk for Bipolar Disorder

Abstract

Objective: Depression and brief periods of manic symptoms are linked to a significant risk of progression to bipolar disorder (BD) in children who have a first-degree relative with BD I or II. However, little evidence exists to guide the pharmacologic management of children with these high-risk phenotypes. We propose a pharmacological treatment algorithm for high-risk youth and present results on its use in a study of children with a first-degree relative with BD.

Methods: Subjects were 40 youth (mean 12.7 years, range 9-17 years) who had (1) a first-degree relative with lifetime history of BD I or II, (2) DSM-IV-TR diagnoses of BD not otherwise specified, major depressive disorder or cyclothymic disorder, and (3) active symptoms of depression, mania, or hypomania. Participants and their families were enrolled in a randomized trial examining the effects of two psychosocial interventions on the 1-year course of mood disorder. At study intake, participants received a psychiatric evaluation and were offered medications or had existing medications optimized to decrease symptom severity. During the 1-year study, psychiatrists treated participants using a medication algorithm to treat depressive or manic symptoms as well as comorbid anxiety and/or attention-deficit/hyperactivity disorder.

Results: At study entry, 25 of 40 (62.5%) of the participants were taking at least one psychiatric medication. At 1 year, nearly an identical proportion were taking medications (22 of 35, 63%). Independent ratings indicated that in 84.7% of the study visits, physicians maintained adherence to the algorithm. No patients experienced antidepressant- or stimulant-induced mania during the study.

Conclusions: An algorithmic approach to pharmacologic interventions may aid in the management of youth (i.e., age <18) at high risk for BD. Future studies should compare outcomes in high-risk patients receiving algorithm-prescribed treatment versus those receiving treatment as usual.

Clinical trial registration information: Early Family-Focused Treatment for Youth at Risk for Bipolar Disorder; www.clinicaltrials.gov/ ; NCT00943085.

Keywords: antidepressant; antipsychotic; bipolar disorder; early intervention; high risk; mood stabilizer; pediatric; treatment.

Conflict of interest statement

Dr. Schneck has received research support from the National Institute of Mental Health and the Crown Family Foundation. Dr. Chang is an unpaid consultant for GlaxoSmithKline, Lilly, and Bristol Myers Squibb. He is on the data safety monitoring board for Sunovion. In the past 3 years, he has received research support from GlaxoSmithKline and Merck, and has been a consultant for Actavis and Janssen. Dr. Singh receives research support from the National Institute of Mental Health, the Office of Research in Women's Health, Brain and Behavior Research Foundation, Janssen, Neuronetics, and the Stanford Child Health Research Institute. Dr. Delbello has received research support from Otsuka, Lundbeck, Purdue, Sunovion, Pfizer, Johnson and Johnson, Supernus, Amarex, and AssureRx. She has also served as a consultant or on an advisory board, or received honoraria from Pfizer, Lundbeck, Sunovion, Supernus, Takeda, Johnson and Johnson, Neuronetics, and Akili. Dr. Miklowitz has received research support from the NIMH, American Foundation of Suicide Prevention, Brain and Behavior Research Foundation, Carl and Roberta Deutsch Foundation, Kayne Family Foundation, Knapp Family Foundation, Attias Family Foundation, Danny Alberts Foundation, and Max Grey Foundation; and book royalties from John Wiley and Sons and Guilford Press.

Figures

FIG. 1.

Initial decision making is by mood diagnosis (unipolar versus bipolar disorder not otherwise specified), then by presenting mood symptoms, then by history of antidepressant-induced mania. Mood symptoms are treated first, followed by reassessment and treatment (if necessary) of comorbid conditions. *Especially if comborbid ADHD present. **Especially if family history of lithium response. †Check EKG if doses > 600 mg. ADHD, attention-deficit/hyperactivity disorder; ARIP, aripiprazole; ASN, asenapine; ATX, atomoxetine; BUP, bupropion; CBZ, carbamazepine; CIT, citalopram; CNZP, clonazepam; DUL, duloxetine; DVX, divalproex; ESC, escitalopram; FLUV, fluvoxamine; GBP, gabapentin; LIT, lithium; LTG, lamotrigine; LUR, lurasidone; MAS, mixed amphetamine salts; MPH, methylphenidate; OLZ, olanzapine; OXC, oxcarbazepine; PAL, paliperidone; QUE, quetiapine; RIS, risperidone; VFX, venlafaxine; ZIP, ziprasidone.