Challenging recent claimslinking antidepressant use to suicidal behavior, a new UCLA study shows thatAmerican suicide rates have dropped steadily since the introduction of Prozacand other serotonin reuptake inhibitor (SSRI) drugs.In research published Feb. 1 in the journal Nature Reviews Drug Discovery, theauthors caution that regulatory actions to limit SSRI prescriptions mayactually increase death rates from untreated depression, the No. 1 cause ofsuicide.
"The recent debate has focused solely on apossible link between antidepressant use and suicide risk without examining thequestion within a broader historical and medical context," said Dr. JulioLicinio, a professor of psychiatry and endocrinologyat the David Geffen School of Medicine and a researcher at the UCLA Neuropsychiatric Institute. "We feared that the absence oftreatment may prove more harmful to depressed individuals than the effects ofthe drugs themselves."
"The vast majority of people who commit suicidesuffer from untreated depression," he said. "We wanted to explore a possibleSSRI-suicide link while ensuring that effective treatment and drug developmentfor depression were not halted without cause."
Licinio worked with fellow psychiatrist Dr. Ma-Ling Wong toconduct an exhaustive database search of studies published between 1960 and2004 on antidepressants and suicide. The team reviewed each piece of researchin great detail and created a timeline of key regulatory events related toantidepressants. Then they generated charts tracking antidepressant use andsuicide rates in the United States.
Whatthey found surprised them.
"Suiciderates rose steadily from 1960 to 1988 when Prozac, the first SSRI drug, wasintroduced," Licinio said. "Since then, suicide rateshave dropped precipitously, sliding from the eighth to the 11th leading causeof death in the United States."
Severallarge-scale studies in the United States and Europe also screened blood samplesfrom suicide victims and found no association between antidepressant use andsuicide.
"Researchersfound blood antidepressant levels in less than 20 percent of suicide cases," Licinio said. "This implies that the vast majority ofsuicide victims never received treatment for their depression."
"Ourfindings strongly suggest that these individuals who committed suicide were notreacting to their SSRI medication," he added. "They actually killed themselvesdue to untreated depression. This was particularly true in men and in peopleunder 30."
Licinioand Wong fear that overzealous regulatory and medical reaction, publicconfusion and widespread media coverage may persuade people to stop takingantidepressants altogether. They warn that this would result in a far worsesituation by causing a drop in treatment for people who actually need it.
The UCLA study also looked at other reasons thatmay contribute to suicidal behavior by people taking SSRIsfor depression.
Before the introduction of SSRIs,patients taking early drug treatments for depression were susceptible tooverdoses and serious side effects, such as irregular heart rates and bloodpressure increases. As a result, doctors prescribed the drugs in small dosesand followed patients closely.
In contrast, toxic side effects are rare in SSRIs. Physicians often prescribe the drugs in larger dosesand may not see the patient again for up to two months. This scenario, Licinio warns, can set the stage for suicide risk.
"When people start antidepressant therapy, thefirst symptom to be alleviated is low energy, but the feeling that life isn'tworth living is the last to go," he said. "Prior to taking SSRIs,depressed people may not have committed suicide due to their extreme lethargy.As they begin drug therapy, they experience more energy, but still feel thatlife isn't worth living. That's when a depressed person is most in danger ofcommitting suicide."
Liciniostresses the need for even closer monitoring of SSRI use by children.
"The only antidepressant proven to be effectivefor treating children with depression is Prozac," he said. "Children shouldreceive Prozac only and should be followed very closely by their physiciansduring treatment."
Funding from the National Institute of GeneralMedical Sciences and an award from the Dana Foundation supported the research.
Depressionis a complex disorder that affects some 10 percent of men and 20 percent ofwomen in the United States during their lifetime. Ten percent to 15 percent ofdepressed people commit suicide. Depression plays a role in at least one-halfof all adult suicides and in 76 percent of suicides committed by children.Suicide is the most common cause of death in children age 5 to 14, the thirdmost common cause of death in people age 15 to 24 and the fourth most commoncause in people age 25 to 44.
TheUCLA Neuropsychiatric Institute is aninterdisciplinary research and education institute devoted to the understandingof complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and thecauses and consequences of neuropsychiatricdisorders. More information is available online at http://www.npi.ucla.edu/.