Bipolar Disorder Treatment in Children and Teens

Divalproex (Depakote) No Better than Lithium in Child/Teen Bipolars: In an 18-month DB PC study of youths ages 5-17 with bipolar I or II disorder initially treated with lithium and divalproex until in remission for 4 weeks,  divalproex alone did no better than lithium alone in survival time until emerging symptoms of relapse or survival time until discontinuation for any reason. Double-Blind 18-Month Trial of Lithium Versus Divalproex Maintenance Treatment in Pediatric Bipolar Disorder. Findling RL, McNamara NK, et al. Case Western Reserve University. J Am Acad Child Adolesc Psychiatry. 2005 May;44(5):409-417. Ed: Adult research has found a much higher suicide rate and greater weight gain with divalproex than lithium. 

2-5 Year-Olds Being Treated in Wisconsin: Diagnosis of bipolar disorder (BPD) in preschool children is controversial. In a report of 31 patients, ages 2-5 years, identified by chart review at a pediatric bipolar clinic, there was a 2:1 male:female ratio, with an average age of symptom onset of 3 years. Most frequent presenting symptoms (100%) included irritability, increased energy, and aggression. Prominent symptoms (>80%) included euphoria, grandiosity, decreased need for sleep, pressured speech, and distractibility. ADHD was reportedly present in 80%. Twenty-one of the 31 reported prior treatment attempts with either a stimulant or antidepressant without the protective benefit of a mood stabilizer, and of these, 13 (62%) reported a worsening of mood symptoms during that treatment period. Twenty-six of 31 were initially treated with a mood stabilizer, primarily valproic acid, with a significant decrease in manic symptoms (p=0.03) following initial treatment. Long-term treatment demonstrated continued improvements from baseline (p=0.01). The diagnosis of preschool bipolar disorder presenting with mania: open pharmacological treatment. Scheffer RE, Niskala Apps JA. Children's Hospital of Wisconsin, Milwaukee. J Affect Disord. 2004 Oct;82 Suppl 1:S25-34. Ed: How many of these children developed manic type symptoms due to stimulants?  I worry that we are over-medicating both children and adults.

17% of ADHD Boys Called Bipolar; Illness Chronic: In a study of 128 ADHD boys followed over 4 years, 17% met criteria for bipolar disorder at the baseline assessment. Less than 20% of boys attained functional remission or euthymia over the entire time. A prospective follow-up study of pediatric bipolar disorder in boys with attention-deficit/hyperactivity disorder. Biederman J, Mick E, Faraone SV, et al. Harvard-MGH. J Affect Disord. 2004 Oct;82 Suppl 1:S17-23.

Mood Stabilizers Thought Better for Mania: In a small retrospective study of 59 children with DSM-III-R  mania, 75% still had some evidence of maniclike symptoms during follow-up. The use of mood stabilizers predicted decreases in manic symptoms (RR = 4.9). However, improvement was slow and associated with a substantial risk for relapse. Use of antidepressant, antipsychotic, and stimulant medications was not associated with improvement. The naturalistic course of pharmacologic treatment of children with maniclike symptoms: a systematic chart review. Biederman J, Mick E, et al. Massachusetts General Hospital. J Clin Psychiatry. 1998 Nov;59(11):628-37. Ed: This report is so small and with no controls that it's findings don't mean a lot other than they reflect the thinking and experience of Harvard child psychiatrists at that moment in time.

Stimulants May Cause Mania in Many ADHD Children: The onset of mania was linked temporally in 21% of 82 juveniles to the starting stimulant medication. Faedda GL, Glovinski IP, Austin NB et al. Treatment emergent mania in pediatric manic depressive illness: role of antidepressants and stimulants. Presented at the 1^st annual Pediatric Bipolar Disorder Conference; March 21-22, 2003; Washington, DC. (Ed: This is a preliminary report, but its findings are very worrisome.)

Anti-Depressants May Be Worse: Researchers reviewed all consecutive admissions with a diagnosis of bipolar disorder to a university-affiliated children's hospital, and collected information regarding previous exposure to antidepressants and stimulants. The mean age of diagnosis of bipolar disorder in our cohort was 12. Children who received prior antidepressant and/or stimulant treatments had an earlier bipolar diagnosis (age 10.7) than children never exposed to these medications (12.7; p = .099). Stimulants appeared to be tolerated for a longer duration than antidepressants (55 months vs. 6.7 months, p = .0001). Children exposed to antidepressants appear to be diagnosed with bipolar disorder earlier than those never exposed to these medications. Antidepressant exposure in bipolar children. Cicero D, El-Mallakh RS, et al. University of Louisville School, Kentucky. Psychiatry. 2003 Winter;66(4):317-22. Ed: Unfortunately, I don't know how many children were in this study. Small, retrospective studies are much less reliable.

Stimulants for ADHD Appear to Have Made Later Mania Worse: In a small retrospective study of 80 adolescents hospitalized with Bipolar disorder, manic or mixed, assessed severity of hospital course, and compared groups according to current/past stimulant or antidepressant treatment, the lifetime ADHD rate was 49%; 35% of patients had exposure to stimulants and 44% to antidepressants. Stimulant-exposed patients were younger than non-exposed (13.7 vs. 15.1, P=0.002). Only stimulant exposure was associated with worse hospitalization course (P=0.02). Stimulant-exposed BP-adolescents may have more severe illness course not fully explained by ADHD comorbidity. Severity of bipolarity in hospitalized manic adolescents with history of stimulant or antidepressant treatment. Soutullo CA, DelBello MP, et al. University of Cincinnati. J Affect Disord. 2002 Aug;70(3):323-7.

Topiramate No Benefit for Child/Teen Bipolars: In a DB PC study of 56 children and adolescents with bipolar disorder type I, at four weeks all but two measures showed no benefit from topiramate. The study was stopped early because a larger study of adult bipolar disorder found no benefit. Topiramate side-effects included decreased appetite, nausea, diarrhea, and paresthesia. A Pilot Controlled Trial of Topiramate for Mania in Children and Adolescents With Bipolar Disorder. Delbello MP, Findling RL, et al. University of Cincinnati, University Hospitals of Cleveland, Johnson & Johnson Pharmaceutical; and Ortho-McNeil Pharmaceutical. J Am Acad Child Adolesc Psychiatry. 2005 Jun;44(6):539-547. Ed: This study shows the disturbing mixing of university and drug industry staff.