NE: A Complicated Link Between Aggression and Antidepressant Drugs

NYAPRS Note: Many Americans describe the great benefits of taking psychiatric medications….but there is reason to consider some instances when they might potentially cause the very kind of aggression for which court ordered medication is intended to address.

A Complicated Link Between Aggression and Antidepressant Drugs

by Angela Herring Northeastern October 9, 2012

Nearly half a mil­lion chil­dren in the U.S. take anti­de­pres­sants. In 2007, the Cen­ters for Dis­ease Con­trol and Pre­ven­tion released a warning for flu­ox­e­tine, one of the most highly pre­scribed psy­chi­atric med­ica­tions. The drug’s pri­mary com­pound seemed to be causing a host of neg­a­tive side effects in a subset of the young users.

“It’s hap­pening,” said Rich Mel­loni <> , pro­fessor of psy­chology <> and director of the Pro­gram in Behav­ioral Neu­ro­science <> in the Col­lege of Sci­ence <> . “Kids are becoming irri­tated, aggres­sive, impul­sive, agi­tated, hos­tile. So you ask the ques­tion: Why?” As behav­ioral neu­ro­bi­ol­o­gists, Melloni’s team is using ado­les­cent animal models to gain an under­standing of why these neg­a­tive side effects occur. Their find­ings <> are pub­lished in this month’s issue of the journal Behav­ioral Neuroscience.

First, he and his research team admin­is­tered reg­ular doses of flu­ox­e­tine to healthy ado­les­cent ham­sters. The ani­mals received either a low, mod­erate or high dosage, equiv­a­lent to what a human ado­les­cent would receive to treat con­di­tions such as anx­iety, depres­sion or obsessive-compulsive dis­order, respectively.

They then observed the ham­sters’ behavior when pre­sented with an intruder — or the mere scent of an intruder — in their cage. Ham­sters that received the low dosage con­sis­tently demon­strated sig­nif­i­cant increases in aggres­sive behavior.

Next the researchers looked at the ham­sters’ brains. They were sur­prised by what they found.

Mel­loni said that when a mol­e­cule called vaso­pressin is present at high levels in the brain, the aggres­sion system works in over­drive. Another mol­e­cule, sero­tonin, has the oppo­site affect.

“Think of sero­tonin as your brake for aggres­sion and vaso­pressin as your gas,” said Mel­loni. If you want to go fast, he said, you can press on the gas, ease off the brake, or engage in a com­bi­na­tion of the two. Flu­ox­e­tine, so to speak, is designed to push on the brake in order to help people deal with the symp­toms of depres­sion. But the aggres­sive ham­sters’ brains had prob­lems with both their gas pedals and their brakes.

Flu­ox­e­tine is a “sero­tonin reup­take inhibitor,” meaning that it increases sero­tonin levels by pre­venting the mol­e­cule from being reab­sorbed by the body. Lower sero­tonin has been linked to depres­sive symp­toms in some patients.

But other neu­ro­log­ical sys­tems also con­tribute to depres­sion, such as the mol­e­cules dopamine and nor­ep­i­neph­rine. When these sys­tems are impaired, patients can show sim­ilar symp­toms as if they had an impaired sero­tonin system.

“Take that kid that presents with the same symp­toms, but he has a dopamine or nor­ep­i­neph­rine problem,” said Mel­loni. “But when you give him a sero­tonin drug, he may get aggres­sive, he may get worse.”

Melloni’s find­ings sug­gest that the chil­dren who expe­ri­ence the aggres­sive side effects of flu­ox­e­tine may not have begun with an impaired sero­tonin system at all. “There’s the like­li­hood,” said Mel­loni, “that by virtue of the fact that our clin­ical diag­nosis is not based in neu­ro­bi­ology, but rather in symp­to­mology, that we may be giving kids a sero­tonin drug inappropriately.”

The next step in the research is to per­form the same tests on ham­sters with “ruined” sero­tonin sys­tems. “Then let’s give these impaired ham­sters [flu­ox­e­tine] and see if they become aggres­sive,” Mel­loni said. “My guess is they are not going to be.”