To our knowledge, this is the first study examining the long-term outcome of anxiety disorders and the factors that predict onset of new anxiety disorders among youth with bipolar disorder. Present findings indicate that most anxiety disorders diagnosed at intake continued during the follow-up and were of the same type. Moreover, about 50% of the youth had persistent anxiety, particularly GAD. The persistence of anxiety disorders was associated with multiple anxiety disorders, less follow-up time euthymic, less comorbid conduct disorder, and less treatment with antimanic and antidepressant medications. Twenty-five percent of the sample who did not have an anxiety disorder at intake developed new anxiety disorders during follow-up, most commonly GAD. The onset of new anxiety disorders was significantly associated with being female, lower socioeconomic status, presence of ADHD and substance use disorders, and more follow-up time with manic or hypomanic symptoms.
Since no other pediatric and adult longitudinal studies that have assessed the outcome of anxiety disorders in bipolar disorder, we compared our results with existing literature on the course of anxiety disorders in youth and adults without bipolar disorder. Similar to our findings, results from longitudinal studies in youth with anxiety disorders have also shown that, with the exception of separation anxiety disorder, most anxiety disorders, and especially GAD,24,25,28,29
tend to continue into adulthood.29–32
Also, evidence for the homotypic continuation of the anxiety disorders has been reported,33,34
and, in concordance with our results, multiple anxiety disorders35
predicted higher persistence of anxiety disorders. In contrast with other studies36,37
which mainly included males, we found that persistence of anxiety was associated with less comorbid conduct disorder. This finding might be explained by the fact that there were no differences in the proportion of males and females in the Course of Outcome of Bipolar Youth study.38
The persistence of anxiety over time may explain in part the high association between anxiety disorders and bipolar disorder and could be a unique factor that negatively influences bipolar disorder severity and prognosis6–8,11
compared to other comorbid conditions such as ADHD and substance use disorders. Furthermore, our results and those of 1 epidemiologic study in youth39
give evidence that the relationship between anxiety disorders and bipolar disorder severity may be bidirectional, as ongoing symptoms of mania or hypomania are associated with persistence and the onset of new anxiety disorders.
The results of our study together with the fact that pediatric anxiety disorders may continue into adulthood and that anxiety disorders worsen the course of bipolar disorder6,7
indicate the need for early identification and treatment of these disorders in youth with bipolar disorder. Current evidence-based treatments for anxiety disorders show that cognitive-behavioral therapy (CBT) and the selective serotonin reuptake inhibitors (SSRIs), and in particular their combination, are efficacious for the acute treatment of anxiety in youth.40
Although we know that CBT is efficacious for youth with anxiety disorders, youth with comorbid bipolar disorder have been excluded from these trials, and thus we do not have data on its efficacy for this population. Moreover, even if the SSRIs are efficacious and well tolerated for youth with anxiety, we do not know the efficacy and tolerability of these medications for youth with bipolar disorder and anxiety. Since there are no randomized controlled trials comparing CBT, SSRIs, or the combination of both treatments in youth (and adults) with anxiety and bipolar disorder, we feel these studies are necessary. Such studies would inform clinical practice, and answer a very important question about the relative efficacy of CBT, SSRIs, and/or the combination, for youth with the common and impairing presentation of comorbid bipolar disorder and anxiety.
About one-quarter of the sample developed new anxiety disorders during the follow-up. Similar to findings in the pediatric and adult literature, female sex41,42
and lower socioeconomic status41,43
increased the risk for new anxiety disorders, particularly GAD.41,44
Our findings are also consistent with the epidemiologic literature in which anxiety disorders are more prevalent in females,30,43
especially GAD in adolescent females.41,45
Epidemiologic as well as clinical studies have shown that youth46–49
with bipolar disorder are at high risk for substance use disorders. Also, both bipolar disorder and substance use disorders are strongly associated with anxiety.52
Similarly, our findings showed that bipolar disorder youth with substance use disorders or ADHD53
were at high risk for onset of new anxiety disorders, suggesting that early recognition and treatment of these disorders may prevent the development of new anxiety disorders.
These above-noted results need to be taken in the context of the limitations of this study. First, no psychiatric control group was included. Thus, we cannot conclude that anxiety disorders are more common in youth with bipolar disorder than in youth with other childhood psychiatric disorders (eg, major depressive disorder). However, other pediatric and adults studies have consistently shown that anxiety disorders are more common in bipolar disorder than in other psychiatric disorders.54,55
Second, the effects of treatment were not analyzed. Finally, since subjects were a referred sample, findings may not apply to other populations.
In summary, most anxiety disorders persisted during the follow-up and a substantial group of subjects developed new anxiety disorders. Consistent with the literature for other disorders (eg, major depressive disorder),56
we found that different factors were associated with the persistence and the onset of new anxiety disorders. Early identification and appropriate management of these risk factors may improve the course of bipolar disorder youth. Randomized controlled trials are warranted to evaluate whether existing treatments known to be efficacious for anxiety disorders particularly psychosocial treatments, such as CBT, that are not associated with inducing mood instability, are equally efficacious and tolerable for youth with comorbid bipolar disorder and anxiety disorders.