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Editorial   |    
Longitudinal Course of Pediatric Bipolar Disorder
Boris Birmaher, M.D.
Am J Psychiatry 2007;164:537-539. doi:10.1176/appi.ajp.164.4.537

Consistent with Kraepelin’s early descriptions (1), it is now recognized that bipolar disorder may become manifest during childhood and adolescence (2–4). However, the diagnosis of children with this disorder may be difficult because pediatric bipolar disorder usually manifests with rapid mood changes, and therefore many children do not have the currently required DSM-IV duration of symptoms to fulfill diagnosis for bipolar I disorder or bipolar II disorder. Furthermore, developmental issues influencing the clinical picture of bipolar disorder in youths, the difficulties children and adolescents have in verbalizing their emotions, and the high rates of comorbid disorders with symptoms that overlap with bipolar disorder account for the complexity and current controversies in diagnosing children and adolescents with bipolar disorder.

Nonetheless, pediatric bipolar disorder significantly affects the normal psychosocial development of the child and increases the risk for suicide and substance abuse as well as for behavioral, academic, social, and legal problems (2–4). Despite these negative consequences and the fact that up to 60% of adults with bipolar disorder report the onset of their mood symptoms before age 20 (2–4), there are doubts regarding the existence of this disorder in youths. Prospective follow-up studies of children with presumptive bipolar disorder may help validate this disorder. Moreover, knowledge of the natural course and factors associated with the onset and recurrences of bipolar disorder may be useful for devising preventative strategies and improving acute and maintenance treatments.

In this issue of the Journal, Melissa P. DelBello, M.D., et al. evaluated the 1-year outcome after discharge from an inpatient unit of 71 bipolar I disorder adolescents admitted for their first manic or mixed episode. Eighty-five percent (60/71) had syndromic recovery in an average period of 27 weeks after the onset of their index episode. However, of these subjects, about 52% (31/60) had at least one syndromatic recurrence 17 weeks on average after they recovered.

Although there are methodological differences among the current pediatric prospective naturalistic studies, other studies have also shown that 70% to 100% of children and adolescents with bipolar disorder will eventually recover (e.g., no significant symptoms for 2 months) from their index episode (2, 4–6). However, of those who recover, up to 80% experience one or more recurrences in a period of  2 to 5 years. These studies as well as retrospective reports have shown high morbidity and mortality from pediatric bipolar disorder: high rates of hospitalizations and health service utilization; psychosis; suicide attempts and completion; switch from bipolar disorder, not otherwise specified, to bipolar I or II disorder and from bipolar II disorder to bipolar I disorder; substance abuse; unemployment; legal problems; and poor academic and psychosocial functioning. Ongoing bipolar disorder symptoms also have negative impact on the family, marital, and sibling relationships as well as on family finances. The considerable impairment in psychosocial functioning reported in these studies is not exclusively due to their use of clinical cohorts, because similar findings have been reported in bipolar disorder adolescents never referred for treatment (7).

DelBello et al. report that the comorbid presence of attention deficit hyperactivity disorder (ADHD), anxiety disorders, low socioeconomic status, and poor adherence to pharmacological treatment was associated with longer time to recovery. Alcohol use disorder, lack of psychotherapy treatment, and use of antidepressants were associated with shorter time to recurrence. In addition to these factors, other studies have also reported that early age of onset, long duration, mixed- or rapid-cycling episodes, psychosis, subsyndromal symptoms, exposure to negative life events, and family psychopathology are associated with worse longitudinal course (2, 4–6).

Bipolar disorder is not only manifest by punctuated recovery and recurrences, but also by ongoing fluctuating syndromal and subsyndromal symptoms (2, 4–6). Thus, there is need for complementary analyses beyond the results provided by simple survival analyses. DelBello et al. show that during the year of follow-up after their hospitalization, bipolar disorder adolescents spent 38% of their time with syndromic symptoms (mainly mixed symptoms), 46% of the time with subsyndromal symptoms, and 16% without symptoms. A recent 2-year follow-up study of children and adolescents with bipolar spectrum disorders (bipolar I disorder; bipolar II disorder; and bipolar disorder, not otherwise specified) showed that, approximately 60% of the observation time, bipolar disorder youths experienced syndromal and subsyndromal bipolar disorder symptoms, particularly depressive and mixed symptoms and repeated changes in symptom polarity (5). These rapid fluctuations in mood appear to be more accentuated than in adults with bipolar disorder and may explain, at least in part, the difficulties encountered diagnosing and treating bipolar disorder symptoms in youths (5).

DelBello et al. also demonstrate that although 85% of adolescents showed symptomatic recovery, only 39% of adolescents achieved functional recovery. These results and the time lag between the symptomatic and functional recovery indicate the need for treatments that will increase the rate and the speed of functional recovery as well as for treatments that target other environmental (e.g., family psychopathology, exposure to negative events) and child-specific factors (e.g., comorbid ADHD, substance abuse, cognitive style). Since substance abuse tends to develop after the onset of bipolar disorder (2, 4), its early detection and prevention is important because of its deleterious effects on the course of bipolar disorder.

An average of 10 years elapse before bipolar disorder is diagnosed and treatment begins (4). For each year of illness, bipolar disorder youths have a 10% lower likelihood of recovery (5), which emphasizes the need for early recognition and treatment of children and adolescents to ameliorate ongoing syndromal and subsyndromal symptoms and to reduce or prevent the serious psychosocial morbidity that usually accompanies this illness. Unfortunately, as shown by DelBello et al. and others (2, 4), a large proportion of subjects do not adhere to pharmacological treatment and thus experience even more recurrences. Many bipolar disorder children require multiple medications (2–5, 8) that may negatively influence their own and their parents’ willingness to continue treatment. Also, children and their families may discontinue the pharmacological treatment because of side effects, break through of depression or mania, cost, or, paradoxically, because the child is transiently doing well and they do not see a good reason to continue treatment. Thus, thorough education; frequent follow-ups and communication with the child, the family, and teachers; easy accessibility to treatment; and appropriate and reasonable cost medical coverage are all required. Also, as reported by DelBello et al., successful treatment of comorbid disorders may improve adherence to treatment.

DelBello et al. found that antidepressants were associated with shorter time for syndromic recurrences. Although controversial, other studies have also showed increased recurrences with the use of antidepressants in bipolar disorder subjects (2, 4, 8). These findings, together with the small but clinically important finding that antidepressants may increase the risk for suicide behaviors, indicate the need for caution with this type of medication in bipolar disorder youths. However, in naturalistic studies, such as the DelBello et al. study, antidepressants may have been prescribed because subjects were already depressed and thus were already at high risk to manifest suicide ideation.

Interestingly, DelBello et al. report that the use of psychotherapy for bipolar disorder youths was accompanied by longer asymptomatic periods. Similar findings have been reported in studies of family focus therapy in youths and adults (4, 8, 9). It is clear that comprehensive treatment planning that addresses the relapsing course of the illness and its comorbid factors, including other illnesses, family psychopathology, and traumatic events, is warranted. Outcomes to be assessed should include not only the symptoms, but also the child’s cognitive development and social and coping skills.

1.Kraepelin E: Manic Depressive Insanity and Paranoia. London: E & S Livingstone, 1921
 
2.Birmaher B, Axelson D, Pavuluri: Pediatric Bipolar Disorder, in Lewis’ Child and Adolescent Psychiatric: A Comprehensive Textbook, 4th Edition. Edited by A. Martin and F. R. Volkmar. Baltimore, Lippincott Williams & Wilkins (in press)
 
3.Axelson D, Birmaher B, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Bridge J, Keller M: Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry 2006; 63:1139–1148
 
4.Pavuluri MN, Birmaher B, Naylor M: Pediatric bipolar disorder: ten year review. J Am Acad Child Adolesc Psychiatry 2005; 44:846–871
 
5.Birmaher B, Axelson D, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Keller M: Clinical course of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry 2006; 63:175–183
 
6.Geller B, Tillman R, Craney J, Bolhofner K: Four-year prospective outcome and natural history of mania in children with a prepuberial and early adolescent bipolar disorder phenotype. Arch Gen Psychiatry 2004; 61:459–467
 
7.Lewinsohn PM, Klein DN, Seeley JR: Bipolar disorder during adolescence and young adulthood in a community sample. Bipolar Disord 2000; 2:281–293
 
8.Kowatch RA, Fristad M, Birmaher B, Wagner KD, Findling RL, Hellander M, Child Psychiatric Workgroup on Bipolar Disorder: Treatment guidelines for children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005; 44:213–235
 
9.Miklowitz DJ, George EL, Axelson DA, Kim Ey, Birmaher B, Schneck C, Beresford C, Craighead WE, Brent DA: Family-focused treatment for adolescents with bipolar disorder. J Affect Disord 2004; 82(suppl 1):S113–128
 

Address correspondence and reprint requests to Dr. Birmaher, University of Pittsburgh Medical Center and Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213; birmaherb@upmc.edu (e-mail).

Dr. Birmaher reports no competing interests.

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References

1.Kraepelin E: Manic Depressive Insanity and Paranoia. London: E & S Livingstone, 1921
 
2.Birmaher B, Axelson D, Pavuluri: Pediatric Bipolar Disorder, in Lewis’ Child and Adolescent Psychiatric: A Comprehensive Textbook, 4th Edition. Edited by A. Martin and F. R. Volkmar. Baltimore, Lippincott Williams & Wilkins (in press)
 
3.Axelson D, Birmaher B, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Bridge J, Keller M: Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry 2006; 63:1139–1148
 
4.Pavuluri MN, Birmaher B, Naylor M: Pediatric bipolar disorder: ten year review. J Am Acad Child Adolesc Psychiatry 2005; 44:846–871
 
5.Birmaher B, Axelson D, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Keller M: Clinical course of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry 2006; 63:175–183
 
6.Geller B, Tillman R, Craney J, Bolhofner K: Four-year prospective outcome and natural history of mania in children with a prepuberial and early adolescent bipolar disorder phenotype. Arch Gen Psychiatry 2004; 61:459–467
 
7.Lewinsohn PM, Klein DN, Seeley JR: Bipolar disorder during adolescence and young adulthood in a community sample. Bipolar Disord 2000; 2:281–293
 
8.Kowatch RA, Fristad M, Birmaher B, Wagner KD, Findling RL, Hellander M, Child Psychiatric Workgroup on Bipolar Disorder: Treatment guidelines for children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005; 44:213–235
 
9.Miklowitz DJ, George EL, Axelson DA, Kim Ey, Birmaher B, Schneck C, Beresford C, Craighead WE, Brent DA: Family-focused treatment for adolescents with bipolar disorder. J Affect Disord 2004; 82(suppl 1):S113–128
 
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