Researching Drug Interventions in Bipolar Offspring: Current Ongoing Research




Drugs_Clinical_Trials2.jpgLast August, at the Stanford University Medical Center, Packard Research findings reported additional research on drug therapy for juveniles predisposed to bipolar disorder. They had found that children with psychiatric problems – who appear to be at high risk for bipolar disorder – already had done well on a mood-stabilizing drug. This was landmark research, in that it was the first study to examine youngsters apparently predisposed to contracting bipolar disorder.

Researchers at the Stanford University Medical School and at the Lucile Packard Children’s Hospital found that figuring the appropriate medication dosages for such children was vital, because previous prescribed drug protocols stressed only stimulants and antidepressants, which are, in fact, known to exacerbate or cause manic episodes, in adults. In the August issue of the Journal of Clinical Psychiatry, the researchers published their results, which determined that over three-fourths of such at-risk juveniles indicated mood stabilization, following administrations of divalproex. This particular medication has been utilized in the treatment of adult mania. According to Dr. Kiki Chang, assistant professor of psychiatry and behavioral sciences at the School of Medicine and a psychiatrist at Packard Children’s Hospital, the drug basically “cools off the brain.”

Since bipolar disorder significantly impacts approximately 2.2 million Americans, who endure handicapping and debilitating extreme mood swings, it is perhaps a good idea to identify as being at risk those children who have a parent with bipolar disorder and who are already showing signs of other psychiatric manifestations. These researchers did this, including in the study, 23 bipolar offspring between age 6 and 18, who had already been diagnosed with either depression, anxiety or attention-deficit/hyperactivity disorder or ADHD. These were youngsters who did exhibit symptoms of depression or mania but did not actually meet criteria for bipolar I or II. Past research had indicated that children of bipolar parents were at some increased risk, having up to a 24 percent chance of developing bipolar, and also that ADHD may well turn out to be a pretty accurate predictor. At the onset of this specific clinical trial, patients were initially evaluated for manic and depressive symptoms and degree of severity. The children in the study then ceased taking their current meds and underwent divalproex treatment for three months, prior to final study assessment.

Dr. Chang noted that while no placebo control group had been in place during this trial, it was still found that, 78 percent of study participants were either “very much improved” or “much improved” in their mood or behavioral disorders. Additionally, 82 percent of the children displayed at the very minimum at least a 50 percent decrease in their symptoms. It was further noted that children diagnosed with depression experienced dramatic improvement within as little as one week. “What was most surprising was how quickly the patients responded, and that patients with depression responded so well to divalproex,” Chang said.

Although traditional drugs will normally foster improvement in children with ADHD or unipolar depression, such a course of treatment can often trigger manic episodes in those young patients susceptible to developing bipolar. Chang and his colleagues in the Stanford Pediatric Bipolar Disorders Program felt that this in of itself was a viable predictor, so they are presently doing follow-up and separate studies, to examine genetic and brain physiological components of bipolar offspring, in order to substantiate this finding and to perhaps find other indicators. These scientists are also conducting more divalproex research, this time utilizing the placebo factor. Other questions the researchers are also concerned with are age of onset and non-drug therapies, such as family interventions, working with a therapist, etc. “Our goal is to identify these children early for treatment and perhaps prevention,” Chang said. “If we can prevent bipolar disease in childhood, we can prevent later treatment resistance and future complications like substance abuse, poor work and school performance, and even suicide.”

So, it would appear plausible that divalproex might not only alleviate bipolar offspring behavior problems and mood swings, but could also possibly prevent, delay or lessen the disorder, Chang commented. Although past research of this drug as localized in lab mice and cell cultures suggest that this medication may assist in actually protecting the brain, such studies had not been attempted before, in either adults or children. At this point, Chang is hopeful that parents and psychiatrists alike will be alerted to the distinct possibility that children predisposed to bipolar disorder will not do well and may have even more mood and behavior problems, if prescribed and administered standard medications for other mood and behavior disorders, such as ADHD and anxiety drugs. Chang wants all involved to realize that there are other more appropriate medical options. “We want to raise awareness about these kids and the idea that perhaps they will be better treated with mood stabilizers,” Chang’s colleagues at Stanford and at the children’s hospital echo his sentiments. They include Kimberly Dienes, research assistant; Christine Blasey, PhD, research psychologist; Nancy Adleman, graduate student; Terence Ketter, MD, associate professor of psychiatry and behavioral sciences; and Hans Steiner, MD, professor of psychiatry and behavioral sciences.

By: Ann Hull, MEd
Editor: Shaheen Lakhan

Ann Hull is an educator, writer, and researcher with over 25 years of experience. She has encountered bipolar disorder in her personal family setting. Moreover, for more than eight years, Ms. Hull taught children in a special education environment, who had been diagnosed with a number of psychiatric disorders, including bipolar, schizophrenia, autism, and Tourette syndrome.

  • parityfanatic

    I find this comment interesting regarding the use of Depakote in Bipolar offspring. I would be curious to know if any significant weight gain was observed in the participants & whether any financial grants were provided by the Depakote manufacturer?
    I would also question whether Lamictal has been considered for research in these offspring.
    I am aware that it has been noted that some rapid-cycling Bipolars do extremely well on Lamictal.
    I also am aware that this drug needs to be boosted slowly & has a significant side effect profile. However, for the most difficult case, it should not be ignored.

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  • Kiki Chang

    To answer your questions, there was some weight gain associated with this trial (mean increase of 8.2 lbs), which was over 3 months. This study was funded by Abbott Laboratories, the makers of Depakote (divalproex). Clearly, further, placebo-controlled research of such interventions in these high risk children are necessary. Unfortunately, our attempts to obtain funding for the larger, placebo-controlled study that would follow the subjects for longer (thus examining prevention of full mania, versus acute improvement) have so far been unsuccessful.

    Lamotrigine may also have neuroprotective potential and we are interested in studying it in this manner. We have finished an open study in adolescents with bipolar depression (Chang et al., 2006) and have a few articles in review regarding the effects of lamotrigine on brain chemistry and function in this population. Note that these subjects were not all bipolar offspring, but a few were. Also, all subjects had bipolar I, II, or NOS.

    And in the interest of further disclosure, I consult to Abbott and GSK and have received research funding from these companies. (GSK makes Lamictal (lamotrigine)). I also consult to AstraZeneca, Shire, and Lilly.

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Shaheen E Lakhan, MD, PhD, MEd, MS, FAAN

Shaheen E Lakhan, MD, PhD, MEd, MS, FAAN, is a board-certified neurologist and pain specialist, medical educator, and scientist. He is the executive director of the Global Neuroscience Initiative Foundation (GNIF). He is a published scholar in biomarkers, biotechnology, education technology, and neurology. He serves on the editorial board of several scholarly publications and has been honored by the U.S. President and Congress.
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