Challenging recent claims linking antidepressant use to suicidal behavior, a new UCLA study shows that American suicide rates have dropped steadily since the introduction of Prozac and other serotonin reuptake inhibitor (SSRI) drugs. Published in the February edition of the journal Nature Reviews Drug Discovery, the authors caution that regulatory actions to limit SSRI prescriptions may actually increase death rates from untreated depression, the No. 1 cause of suicide.
"The recent debate has focused solely on a possible link between antidepressant use and suicide risk without examining the question within a broader historical and medical context," explained Dr. Julio Licinio, a professor of psychiatry and endocrinology at the David Geffen School of Medicine and a researcher at the UCLA Neuropsychiatric Institute. "We feared that the absence of treatment may prove more harmful to depressed individuals than the effects of the drugs themselves."
"The vast majority of people who commit suicide suffer from untreated depression," he added. "We wanted to explore a possible SSRI-suicide link while ensuring that effective treatment and drug development for depression were not halted without cause."
Licinio worked with fellow psychiatrist Dr. Ma-Ling Wong to conduct an exhaustive database search of studies published between 1960 and 2004 on antidepressants and suicide. The team reviewed each piece of research in great detail and created a timeline of key regulatory events related to antidepressants. Then they generated charts tracking antidepressant use and suicide rates in the United States.
What they found surprised them.
"Suicide rates rose steadily from 1960 to 1988 when Prozac, the first SSRI drug, was introduced," said Licinio. "Since then, suicide rates have dropped precipitously, sliding from the 8th to the 11th leading cause of death in the United States."
Several large-scale studies in the United States and Europe also screened blood samples from suicide victims and found no association between antidepressant use and suicide.
"Researchers found blood antidepressant levels in less than 20 percent of suicide cases," said Licinio. "This implies that the vast majority of suicide victims never received treatment for their depression."
"Our findings strongly suggest that these individuals who committed suicide were not reacting to their SSRI medication," he added. "They actually killed themselves due to untreated depression. This was particularly true in men and in people under 30."
Licinio and Wong fear that overzealous regulatory and medical reaction, public confusion and widespread media coverage may persuade people to stop taking antidepressants altogether. They warn that this would result in a far worse situation by causing a drop in treatment for people who actually need it.
The UCLA study also looked at other reasons that may contribute to suicidal behavior by people taking SSRIs for depression.
Before the introduction of SSRIs, patients taking early drug treatments for depression were susceptible to overdoses and serious side effects, such as irregular heart rates and blood pressure increases. As a result, doctors prescribed the drugs in small doses and followed patients closely.
In contrast, toxic side effects are rare in SSRIs. Physicians often prescribe the drugs in larger doses and 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, the first symptom to be alleviated is low energy, but the feeling that life isn't worth 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 that life isn't worth living. That's when a depressed person is most in danger of committing suicide."
Licinio stresses the need for even closer monitoring of SSRI use by children.
"The only antidepressant proven to be effective for treating children with depression is Prozac," he said. "Children should receive Prozac only and should be followed very closely by their physicians during treatment."
Funding from the National Institute of General Medical Sciences and an award from the Dana Foundation supported the research.
Depression is a complex disorder that affects some 10 percent of men and 20 percent of women in the United States during their lifetime. Ten to 15 percent of depressed people commit suicide. Depression plays a role in at least half of 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 third most common cause of death in people age 15 to 24, and the fourth most common cause in people age 25 to 44.
The UCLA Neuropsychiatric Institute is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, and the causes and consequences of neuropsychiatric disorders. See http://www.npi.ucla.edu for more
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