In 2004, the U.S. Food and Drug Administration announced findings that the antidepressant medication Paxil (paroxetine) may increase the risk of suicidal thoughts and behavior in children and adolescents. A member of the class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), Paxil’s safety and effectiveness were well established until that point. The overall risk was statistically very small but was real and troubling enough to necessitate the warning. Researchers have struggled to understand and identify the precise mechanism behind the increased suicide risk. Some important unanswered questions included the following: Why are only adolescents affected? Does dosage alter the risk? Are there ways to lessen or eliminate the risk altogether? Researchers with the Emory University School of Medicine in Atlanta looked at all of these questions and more in a placebo-controlled study of rats and Paxil.
Depression is a complex mental illness with many causes and manifestations. The best treatments call for a multipronged, individualized approach. From a biological point of view, scientists have learned that activity levels in a specific structure of the brain—the locus coeruleus—increase when a person experiences depression. The release of chemicals from the locus coeruleus may result in increased anxiety or unease. One of the effects of SSRI medications, such as Paxil, is to reduce activity in this area of the brain. The Emory University study compared locus coeruleus activity in adult rats and adolescent rats at different dosage levels of Paxil. The classic “swim test” was employed to gauge the relative depression levels of the rats in each group.
The results of the 2-week rat study were significant, in addition to it being the first study of its kind to possibly explain the link between Paxil and suicide risk. The researchers discovered that for the first 4 days of treatment with Paxil, activity in the locus coeruleus of adolescent rats actually increased. This increased activity correlated with both depression that was more pronounced and possibly higher anxiety levels. Results from the swim test reinforced the findings, as the younger rats were more likely to float than attempt to struggle while in the water. Activity levels in the locus coeruleus fell by the 8th day, which is in line with the observation that adolescent humans are at greatest risk of suicide in the early stages of treatment with Paxil.
The study at Emory University only reinforces the warning that Paxil should not be a first choice in the treatment of depression in children and adolescents. However, there is also hope that this dangerous adverse effect may one day be circumvented. If scientists can shed more light on the mechanism behind the increased suicide risk in adolescents taking Paxil, then new therapies or treatment combinations may become possible that eliminate the risk. Depression is difficult to treat, and the threat of relapse is always present. Patient outcomes will only improve as more medications and therapies are made available.
References
- PubMed Health [Internet]. (n.d.). Bethesda (MD): National Library of Medicine. Paroxetine. Retrieved March 8, 2012, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001037/
- West, C. H., Ritchie, J. C., Weiss, J. M. (2010). Paroxetine-induced increase in activity of locus coeruleus neurons in adolescent rats: Implication of a countertherapeutic effect of an antidepressant. Neuropsychopharmacology, 35, 1653-1663.
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