A number of controversies surround the accurate diagnosis and treatment of bipolar disorder in children and adolescents, according to panelists at a symposium at APA’s 2000 annual meeting last month in Chicago.

The symposium was chaired by David Mrazek, M.D., the Yochelson Professor and chair of psychiatry at George Washington University Medical Center. He was joined by several leading researchers and clinicians in the field of bipolar disorder, and Frederick K. Goodwin, M.D., a research professor of psychiatry at George Washington University, served as the discussant.

Mrazek led off the symposium with a review of the genetic hypotheses underlying the heritability of bipolar disorder (BPD). Studies of single-family lines, twins, and adopted children with BPD have established the heritability of BPD, showing it as high as 79 percent in identical twin pairs. Currently, the attempt to establish the genetic basis of BPD is an intense area of research concentration.

According to Mrazek, evidence now suggests that BPD is the result of the interaction of multiple genes. The variety of presentations within BPD are most likely due to the various genes interacting in slightly different ways in different individuals. Several researchers have identified a series of candidate genes that appear to contribute to susceptibility. Their expression increases an individual’s susceptibility to the development of BPD. But, Mrazek said, "they are not genes for bipolar disorder." Mrazek believes that the key is in the interaction between these genes and that through their interaction, the complex signs and symptoms of BPD develop. Someone looking for a single gene that causes BPD is not going to find it. "You can’t have a symphony with only one instrument," Mrazek explained.

Several hypotheses, he continued, have tried to explain the complex interactions, but none has yet been confirmed. Whatever the mechanism of interaction, the implications of identifying genes strongly associated with BPD are extremely controversial. Once markers have been identified for the genes, questioned Mrazek, "should we then use them to test children who, perhaps, have a strong family history of BPD? Then, if a child is shown to carry genes strongly suggestive of the development of BPD, do we then prophylactically start them on medications, mood stabilizers, for example?"

Mrazek envisioned a consultation in the not-too-distant future in which psychiatrists will be asked to review a genetic profile for risk of psychiatric disorders.

Goodwin agreed. Will psychiatrists be able to look at a genetic profile and say for sure that a patient will have BPD? Probably not, thinks Goodwin, a former director of the National Institute of Mental Health. "But," he observed, "the sum of the risk factors and predispositions, along with the environment in which they are acting, will be better known to the diagnostician."

Establishing a genetic profile for bipolar disorder may well dispel some of the current controversy surrounding the accurate diagnosis of BPD in children and adolescents. Peter S. Jensen, M.D., director of the Ruane Center for the Advancement of Children’s Mental Health at the New York State Psychiatric Institute and a professor of child psychiatry at the College of Physicians and Surgeons of Columbia University, discussed these controversies.

Recent reports have indicated that there may be substantial overlap of BPD with attention deficit/hyperactivity disorder (ADHD). In addition, several researchers have suggested that as many as 20 percent of children diagnosed with ADHD should have been more accurately diagnosed with BPD. In contrast, other investigators have argued that the apparent overlap between BPD and ADHD is actually a complex comorbidity, not the inaccurate diagnosis of one or the other.

The controversy, said Jensen, is not a question of whether or not these "overlap" children are presenting with some form of a psychiatric disorder. The question is, What should the disorder most appropriately be called, and what is the treatment? The most common presentation of BPD in prepubertal children is defined by marked impairment; usually nonepisodic, continuous rapid cycling; and a mixed manic picture. There also may be features of ADHD or conduct disorder as its initial signs and symptoms. This certainly differs from the classically defined adult-onset mania marked by discrete episodes of definite mania followed by complete return to baseline.

"Is BPD in children and adolescents," asks Jensen, "developmentally different, and therefore does psychiatry need to define it differently?"

Researchers are divided on the answer. Goodwin sees the diagnosis of BPD in children and adolescents as an intensely evolving science. He favors the idea that BPD in children is a variation of the adult-onset disorder made even more complicated by frequent comorbid conditions.

Following Jensen, Karen D. Wagner, M.D., Ph.D., the Clarence Ross Miller professor and vice chair and director of the division of child and adolescent psychiatry at the University of Texas Medical Branch at Galveston, reviewed the current controversies surrounding the treatment of BPD, given an accurate diagnosis. Questions regarding which drug to start with, which drugs should be combined, and what should be done when patients don’t respond to initial medication therapy were discussed.

"There is a horrible lack of scientific evidence," said Wagner, "to support the known, off-label prescribing that is occurring in kids with BPD."

Although the same drugs are used in children and adolescents as in adults with BPD, there is little research showing they are safe and effective in this population.

Clinical evidence has shown that the side effects of well-known medications used in adults are different when used in children and adolescents. Lithium, divalproex, and carbamazepine have significant side effects in children that make their use difficult. Frequently, for example, children discontinue lithium because of its characteristic side effects: tremor, stomach upset, acne, drowsiness, confusion, weight gain, and the little recognized side effect of frequent urination.

To minimize side effects and maximize efficacy, Wagner suggested starting a child with BPD on lithium or divalproex. If the single drug does not appear to be effective, then she advocates combining the two. If there is still no response, the patient may be switched to carbamazepine. If there is no response to the carbamazepine, lithium can be added. The suggestions continue with the possibility of olanzapine and risperidone or even gabapentin as a drug of last resort in BPD children.

Pharmacotherapy of early-onset BPD, remarked Goodwin, is at least as complicated and somewhat based simply on trial and error, as is therapy in adults.

Goodwin and his copresenters agree that more research must be done so that BPD in children and adolescents can be more accurately characterized and defined. And care must be taken to approach treatment from the perspective of what is known, rather from what is postulated or hypothesized.