When it comes to the link between antidepressants and suicidal behavior in young people, dose may matter quite a bit, a new study suggests.
The Food and Drug Administration has for years required antidepressants to carry warnings that they may increase the risk of suicidal thinking and behavior in children and adults under age 25. The study, published online Monday by the journal JAMA Internal Medicine, finds the risk for deliberate self harm doubles when depressed young people start treatment with higher-than-usual doses.
The finding is one more reason for doctors and families to carefully consider how and whether to use the medications in young people, researchers say.
"One can quibble about how much benefit there is at typical doses, and my sense is that the benefit is modest at best," says the study's lead author, Matthew Miller, a physician at the Harvard School of Public Health. "But there's no evidence that higher initial doses are going to help more than lower doses." Instead, he says, higher doses may only add risk.
For the study, Miller and colleagues looked at the health records of 162,625 privately insured people ages 10 to 64 treated for depression with three popular antidepressants best known by the brand names Celexa, Prozac and Zoloft.
They compared otherwise similar patients — based on the intensity of their depression symptoms, previous self harm and other factors — who got either typical starting doses or higher doses.
The typical starting doses were 20 mg. a day for Celexa and Prozac and 50 mg. a day for Zoloft.
Result: After a year, children, teens and young adults were twice as likely to engage in deliberate self harm if they started at higher doses. Such acts were especially common in the first three months. No such link between starting dose and self harm was found in adults 25 and up.
The number of young people who hurt themselves was 142 out of 21,305. The risk was 1.4% at typical doses and a 3.1% at higher doses.
The reasons for any link between antidepressants and self harm remain unclear; it's also not known why it shows up only in young people. One theory is that the medications give young sufferers new energy to carry out suicide plans; another is that unpleasant side effects trigger suicidal thoughts. Higher doses might make such effects bigger, Miller and his colleagues speculate.
The study adds support to guidelines that call for starting antidepressants at low doses, says David Brent, a professor of psychiatry at the University of Pittsburgh who co-wrote an accompanying editorial. He notes that the study did not look at whether dose escalations over time raised risk.
Brent takes issue with Miller's statement that antidepressants have "modest" benefits in youths. For adults and youths with depression of equal severity, he says, benefits are comparable.
The National Institute of Mental Health says the latest studies suggest "the benefits of antidepressant medications likely outweigh their risks to children and adolescents with major depression." It says that a combination of medication and psychotherapy was most effective in one major study.
The choices can be complex, Brent says: "There is no one right thing to do. It's the obligation of the physician to explain the risks and benefits and for the family to make the decision."
R. Scott Benson, a child psychiatrist in Pensacola, Fla., says some children and teens get put on antidepressants "in too casual a way," without a thorough evaluation of their problems. "We have to make sure their level of depression is serious enough to warrant treatment with an antidepressant," he says. Benson is on the communications committee of the American Psychiatric Association.
Antidepressants are used by 3.7% of children ages 12 to 17 and 6.1% of adults ages 18 to 39, according to the federal Centers for Disease Control and Prevention. Use is higher in older adults.