Bipolar Disorder in Youths

Several recent studies provide some answers to clinically important questions about bipolar disorder in children and adolescents.

Q: Do children with manic symptoms continue to experience mania over time?

Findling and colleagues¹ conducted a 24-month follow-up of 707 children who were 6 to 12 years old when they initially participated in the Longitudinal Assessment of Manic Symptoms study. At baseline, these children had elevated symptoms of mania, but most did not meet criteria for bipolar spectrum disorder. These children were more likely to have depression, ADHD, oppositional defiant disorder, or conduct disorder.

Over 2 years, distinct trajectories of manic symptoms were found for these children. The majority of children (85%) had a reduction of manic symptoms over time, whether they had high or low manic symptom levels initially. About 15% of children had a pattern of high manic symptoms that worsened over time or that decreased sharply but returned to high baseline levels.

The finding that manic symptoms did not worsen and progress to bipolar disorder in most children is very relevant information for clinicians and parents of these children. Further study of prognostic factors is warranted for early identification of the subgroup of children whose manic symptoms progress.

Q: How common are suicidal ideation and suicide attempts in children and adolescents with bipolar disorder?

The rates of suicidal ideation and suicide attempts were investigated using published studies that included 1595 youths with bipolar disorders (bipolar I, bipolar II, and bipolar disorder not otherwise specified [NOS]).² The mean weighted prevalence of current suicidal ideation was 50.4% and past suicidal ideation was 57.4%. Suicide attempts were also common, with a current rate of 25.5% and past rate of 21.3%. The prevalence of suicidal ideation was higher than that for adults with bipolar disorder.

Factors significantly associated with suicide attempts were older age, female sex, early illness onset, more severe illness, mixed episodes, more comorbid disorders, past self-injurious behavior, physical/sexual abuse, family history of suicidality, poor family functioning, and parental depression. Bipolar I disorder and comorbid ADHD were also significantly correlated with suicide attempts. In this literature review, only one small open-label study was found that examined an intervention to reduce suicidal ideation and suicide attempts. Given the high prevalence of suicidal ideation and suicide attempts in youths with bipolar disorder, both prevention and intervention strategies require further attention.

Q: How severe is bipolar depression in children and adolescents?

Van Meter and colleagues³ compared the impact of depressive symptoms with that of manic symptoms on functioning in youths with bipolar disorder. The sample included 54 child and adolescent outpatients with bipolar spectrum disorder (I, II, and NOS). Clinician and parent ratings were obtained using a wide range of scales that assess depressive and manic symptoms, behavior, and quality of life.

Clinician ratings revealed that depressive symptoms in children increased the risk of psychiatric illness, lower self-concept, hopelessness, suicidal ideation, and lower quality of life. Parental ratings showed an association between depressive symptoms in children with problem behaviors and lower quality of life. Manic symptoms as rated by clinicians were associated with greater psychiatric illness and physical well-being. Surprisingly, mania rated by parents was associated with better self-esteem and physical well-being.

These findings confirm earlier reports of the severity of bipolar depression and point to the need for effective treatment of bipolar depression in youths. To date, the majority of medication treatment studies for bipolar disorder in youths have focused on manic or mixed states, and not depression.

Q: Are there any new medication studies for acute treatment of bipolar disorder in youths?

Paliperidone has been evaluated in an 8-week open-label study for the treatment of 15 youths aged 6 to 15 years with bipolar spectrum disorder (I, II, and NOS) with current manic, hypomanic, or mixed symptoms.⁴ Eleven youths (73%) completed the study. Reasons for discontinuation were adverse events (n = 1), lack of efficacy(n = 2), and inability to swallow pills (n = 1). Participants received 3 mg of paliperidone daily or 6 mg daily if they were 12 years or older and weighed more than 45 kg or if medication was clinically indicated.

There was a statistically significant improvement from baseline in Young Mania Rating Scale (YMRS) scores over the course of the study. The improvement in mean YMRS scores was 18.7 points. The 73% who completed the study were rated as much improved or very much improved on symptoms of mania as assessed by the Clinical Global Impression-Improvement Scale.

The most common adverse events were decreased energy, increased appetite, cold/infection/allergy symptoms, headache, and insomnia. There was a statistically significant in-crease in weight from day 1 (mean, 98.1 lb) to end point (102.2 lb), with weight gain ranging from 0 to 12.5 lb. These findings show some preliminary support for paliperidone. However, large controlled trials are necessary to demonstrate the safety and efficacy of paliperidone for the treatment of bipolar disorder in children and adolescents.

Q: Are there any new long-term studies on mood stabilizersfor the treatment of bipolar disorder in youths?

Findling and colleagues⁵ recently investigated the long-term effectiveness of lithium treatment for children and adolescents with bipolar I disorder, manic or mixed. Sixty-one participants initially took part in an 8-week, open-label, monotherapy trial of lithium. Those who had at least a 25% improvement in mania symptoms as assessed by the YMRS were eligible to participate in the second phase of the study.

Forty-one patients entered this long-term phase that ran an average of 15 weeks. The mean lithium concentration at the start of the second phase was 1.1 mEq/L, and it was 1.0 mEq/L at end point. Concomitant psychotropic medication was allowed if clinically indicated: 61% received concomitant medication, mostly for refractory mania symptoms or for comorbid ADHD.

At the end of the long-term study, 68% of patients met criteria for response (50% or greater reduction from phase 1 baseline YMRS score and a much or very much improved Clinical Global Impression-Improvement score); 22% were partial responders, and 10% were nonresponders. The addition of adjunctive psychotropic medication helped patients maintain mood stabilization, but there was no significant improvement in symptoms over the course of the study. These findings demonstrate that more effective treatments are needed to significantly improve symptoms of bipolar disorder in youths.

References:

1. Findling RL, Kafantaris V, Pavuluri M, et al. Post-acute effectiveness of lithium in pediatric bipolar I disorder. J Child Adolesc Psychopharmacol. 2013;23:80-90.

2. Hauser M, Galling B, Correll CU. Suicidal ideation and suicide attempts in children and adolescents with bipolar disorder: a systematic review of prevalence and incidence rates, correlates, and targeted interventions. Bipolar Disord. 2013;15:507-523.

3. Van Meter AR, Henry DB, West AE. What goes up must come down: the burden of bipolar depression in youth. J Affect Disord. 2013 Jun 12; [Epub ahead of print].

4. Joshi G, Petty C, Wozniak J, et al. A prospective open-label trial of paliperidone monotherapy for the treatment of bipolar spectrum disorders in children and adolescents. Psychopharmacology (Berl). 2013;227:449-458.

5. Findling RL, Jo B, Frazier TW, et al. The 24-month course of manic symptoms in children. Bipolar Disord. 2013 Jun 26; [Epub ahead of print].