Pharmacogenomics may change the scope of practice as it relates to the use of antidepressants for patients with bipolar disorder

It is a common and dangerous reaction: Patients with bipolar disorder are often depressed, and so their physician prescribes antidepressants. Instead of the intended euthymia, however, the result is antidepressant-induced mania (AIM).

Joanna M. Biernacka, Ph.D., is a statistical geneticist and a co-principal investigator of the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder. While enrolling patients for a study of whether some persons with bipolar disorder are particularly disposed to a manic response to antidepressant treatment, she and her team of co-investigators began to review the literature.

"There isn't much available," notes Dr. Biernacka. "Five previous pharmacogenomic studies (studies of how variations in the human genome affect response to medications) that examined the antidepressant-induced phenomenon in bipolar patients have limitations that impact the utility of their results." Those limitations include:

  • Small sample sizes
  • Lack of consistently defined AIM phenotype
  • Use of various types of antidepressant medications
  • No indication of whether mood stabilizers were used or rapid cycling occurred
  • Failure to account for the ancestry of study participants, leading to possible confounding by population stratification
  • Diagnoses and subtype patterns that may confound results

Dr. Biernacka and her co-investigators evaluated the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM in "Pharmacogenomics and Antidepressant Induced Mania: A Review and Meta-analysis of the Serotonin Transporter Gene (5HTTLPR) Association," published in the January 2012 issue of the Journal of Affective Disorders (136[1-2]:e21-e29). The study concluded that published data are insufficient to confirm an association between 5HTTLPR and AIM.

New study will use biobank data to study risk factors and predictors

Dr. Biernacka's team plans to use the biobank data to study both the genetic risk factors for bipolar disorder and the genetic predictors that contribute to response to treatment, especially when that response is AIM.

"The biobank has enrolled more than 800 of the 2,000 adults with bipolar disorder we hope will participate," notes Dr. Biernacka. "For this study, we are collecting detailed information about treatments and response to treatments, plus blood samples. We've profiled prior studies. Now we'll expand on them to more fully understand AIM."

The identification of pharmacogenomic predictors of treatment response is expected to aid in the development of pharmacogenomically based treatment algorithms that will enhance outcome and reduce the occurrence of ineffective or suboptimal treatment trials.

"Genetic research will change medicine by helping us understand the complex sets of factors that contribute to treatment response," says Dr. Biernacka. "Pharmacogenomic studies of AIM have very high potential clinical impact, provided that future studies are of adequate sample size and rigorously assess patient characteristics and phenotypes."