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Recent studies cast doubt on this theory, suggesting that scientists have never understood the drugs' effects on the brain.
A growing number of medical researchers say while increasing serotonin retention, SSRIs also indirectly inhibit the neurotransmitter dopamine, causing a chemical imbalance in some users. This has been linked to serious side effects such as akathisia, a severe inner restlessness associated with violent behavior.
Illegal hallucinogens such as ecstasy, LSD and PCP similarly increase serotonin levels and decrease serotonin metabolism.
SSRIs were considered a vast improvement over previous generations of antidepressants, developed in the '50s and '70s, which were found to elevate moods but later deemed acutely toxic with a high risk of overdose.
The first SSRI introduced in the United States was Eli Lilly's Prozac in 1988. Its immediate popularity led to a host of brand-name imitators, from Paxil to Pfizer's Zoloft, Forest Laboratories' Celexa, Solvay Pharmaceuticals' Luvox, Wyeth Pharmaceuticals' Effexor and many others.
All are marketed to treat a range of mental illnesses, including severe depression, post-traumatic stress disorder, social anxiety and obsessive-compulsive disorder. Doctors prescribe them for everything from eating disorders to bed wetting, low self-esteem, nail biting and shyness.
More than 20 million Americans take antidepressants. Last year doctors dispensed 150 million prescriptions in the United States, according to IMS Health, a Connecticut-based health care information company. As much as 70 percent of the drugs are prescribed not by psychiatrists but by general practitioners with no special training in complex mental disorders.
The overall market for antidepressants in the United States exceeds $12.5 billion annually. Sales of Paxil earn GlaxoSmithKline $3 billion a year worldwide.
The debate over SSRIs has raged for 20 years. Drug companies and countless patients who swear by them have been quick to dismiss any suggestion that they may be harmful. Then there are doctors and attorneys who blame the drugs for virtually every seemingly unexplainable violent rampage.
Harvard Medical School psychiatrists were the first to identify a link between SSRIs and aggressive behavior, reporting in 1990 that six adults experienced "intense, violent suicidal preoccupation" within a couple of months of starting Prozac.
An FDA panel dismissed the study. It took 15 years for the agency -- which some criticize as more lapdog than watchdog -- to change its thinking.
FDA drug-safety analyst Andrew Mosholder in 2003 discovered several suicide attempts reported in Paxil trials under the euphemistic heading "emotional liability." Mosholder conducted his own analysis of Paxil and other antidepressants. He found they doubled the risk of suicidal thoughts or behavior in children and adolescents compared to a placebo. Several trials further showed they performed no better than a sugar pill.
The FDA blocked Mosholder from going public, claiming that his study had not been finalized. But his findings were soon leaked to the media.
Based on these revelations, the FDA in the summer of 2003 issued a public health advisory warning that Paxil and other SSRIs may worsen depression and cause suicidal tendencies in kids under 18.
In June 2004, New York Attorney General Eliot Spitzer sued GlaxoSmithKline for allegedly burying studies showing Paxil increased suicidal thoughts and behavior in kids. Central to the case was an internal GlaxoSmithKline document showing the company intended to "manage the dissemination of data in order to minimize any potential negative commercial impact." GlaxoSmithKline denied the charges but settled the suit in August 2004 for $2.5 million and agreed to post its clinical results on the Web.
Later that year the FDA required all antidepressants to carry a black box warning on labels, the agency's strongest kind, to warn of suicide risk in children. Then in May 2006, GlaxoSmithKline issued a statement warning doctors of a heightened risk of suicide in young adults, ages 18 through 30. It marked the first study released by a drug company that showed a connection between antidepressants and suicidal behavior.
This debate has been argued in scores of lawsuits since the late '80s, when Prozac hit the market. Antidepressants have been blamed for prompting the Columbine shootings and countless other killing sprees.
Many of these suits were resolved in 11th-hour settlements, enabling drug companies to avoid the publicity of going to court and nix the risk of confronting a guilty verdict.
One high-profile case pitted the family of Joseph Westbecker against Eli Lilly, claiming the Kentucky man's four-week use of Prozac in 1989 led him to kill eight people. Lilly won the case. But it was later discovered that the drug company doled out huge settlements to all the attack survivors and their attorneys. The judge later changed the official record from a jury verdict in Lilly's favor to dismissal of a settled case.
In 2001 relatives of Donald Schell sued GlaxoSmithKline, claiming the Wyoming man's 48-hour use of Paxil in 1998 led him to kill his wife, daughter and nine-month-old granddaughter. The jury found Paxil was a "substantial factor" and ordered the drug company to pay $6.5 million to surviving relatives. It marked the first and only case won by a plaintiff.
Houston trial lawyer Andy Vickery represented the Schell family. He enjoys a national reputation as the lone attorney to stick it to GlaxoSmithKline on the suicide issue.
Vickery and associate Paul Waldner already have consulted with about 70 women who are convinced that taking Paxil during pregnancy caused serious birth defects.