Once again, antidepressants have been linked to an episode of horrific violence. The New York Times reports that Aaron Alexis, who allegedly shot 12 people to death at a Navy facility in Washington, D.C., earlier this week, received a prescription for the antidepressant trazodone in August.
When I first researched antidepressants almost 20 years ago, I encountered claims that they sometimes triggered violent episodes—for example, a 1989 incident in which a Kentucky man taking fluoxetine (brand name Prozac) shot to death eight co-workers and then himself. I dismissed the claims, reasoning that, because people prescribed psychiatric drugs are disturbed to begin with, it is not surprising that a tiny fraction hurt themselves and/or others.
By 2004, however, in part because of lawsuits that forced pharmaceutical companies to disclose data on adverse effects, the FDA ordered antidepressant manufacturers to include a warning that antidepressants "increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders."
Alexis, who was 34, was reportedly seeking treatment for insomnia when he received his prescription for trazodone. Originally marketed as an antidepressant after its approval by the FDA in 1981, trazodone is also prescribed for anxiety and insomnia. Trazodone was a precursor of the extremely popular selective serotonin reuptake inhibitors (SSRIs); like the SSRIs, trazodone boosts levels of the neurotransmitter serotonin.
A website maintained by the National Institutes of Health states that trazodone and other antidepressants have been associated with "new or worsening depression; thinking about harming or killing yourself, or planning or trying to do so; extreme worry; agitation; panic attacks; difficulty falling asleep or staying asleep; aggressive behavior; irritability; acting without thinking; severe restlessness; and frenzied abnormal excitement."
Could trazodone have played some role in the Navy Yard rampage? I put this question to David Healy, a professor of psychiatry at Cardiff University in England and an authority on side effects of psychiatric medications.* He has testified in numerous court cases involving suicides and homicides whose perpetrators were ingesting antidepressants. Healy is not opposed to psychiatric medications--he prescribes them to his own patients—but he has long been active in pointing out medications' risks. *[Healy and other health-care experts have founded an organization called RxISK to gather data on side effects of drugs. See Postscript.]
Healy responded by email that he "would need to know much more details" to judge whether trazodone might have contributed to this week's massacre. Indeed, as the Times reported, Alexis had displayed signs of mental illness and acted violently well before being prescribed trazodone. In 2004 he fired bullets into a car in Seattle, during what he described later as a "black out" episode. So far, moreover, there are no reports that he had trazodone in his system during his Navy Yard rampage.
But Healy said that, although data on antidepressants and violence are much more scarce than data on suicide, there is evidence that "you can put healthy volunteers on these drugs and some will become violent." A study by the Drug Safety Research Unit in Southampton of paroxetine (Paxil) and fluoxetine (Prozac) involving more than 25,000 subjects showed that one out of every 250 subjects were involved in "a violent episode," including 31 assaults and one homicide, Healy said.
Another study involving more than 9,000 subjects taking the antidepressant paroxetine (Paxil) for depression and other disorders showed that subjects experienced more than twice as many "hostility events" as subjects taking a placebo. Healy added: "I have had clinical experience of at least one older man, with no prior history of violence, who became homicidal after a week on citalopram where the problem cleared up once treatment had stopped."
Healy suspects that the main causal factor behind suicide and violence toward others is increased mental and/or physical agitation, which leads about 5 percent of subjects taking antidepressants to drop out of clinical trials, compared to only 0.5 percent of people on placebos.
In their excellent overview "Antidepressants and Violence: Problems at the Interface of Medicine and Law," published in PLoS Medicine in 2006, Healy and two co-authors note that "serious violence on antidepressants is likely to be very rare." But they call for "more clinical trial and epidemiological data to be made available and for good clinical descriptions of the adverse outcomes of treatment."
They add: "Legal systems are likely to continue to be faced with cases of violence associated with the use of psychotropic drugs, and it may fall to the courts to demand access to currently unavailable data. The problem is international and calls for an international response."
Antidepressants and other psychiatric drugs clearly help alleviate mental illness in some patients. But as I have written previously, such medications may on balance harm patients more than they help. We need better data on the risks that these medications pose not only to patients but also to others.
*Postscript: David Healy and other health-care experts from around the world have formed an organization called RxISK to gather data on adverse effects of pharmaceutical drugs, including violence. The RxISK website calls it "the first free, independent website where patients, doctors, and pharmacists can research prescription drugs and easily report a drug side effect--identifying problems and possible solutions earlier than is currently happening." I hope RxISK succeeds, because we badly need it.
Post-Postscript: For more on links between psychiatric medications and violence, see this 2010 paper in PLOS One, "Prescription Drugs Associated with Reports of Violence Towards Others," and a followup blog post by journalist Robert Whitaker, author of Anatomy of an Epidemic.
Photo: Federal Bureau of Investigation.