Antidepressants are thought to increase the risk of suicide in young people, but that may be caused by starting them on larger doses of the drugs, a study finds.
Children and young adults who started taking selective serotonin reuptake inhibitor antidepressants in higher-than-average doses were twice as likely to attempt suicide as people taking average doses, according to a study published Monday in JAMA Internal Medicine.
Earlier randomized controlled trials found that taking SSRI antidepressants increased suicidal thinking and behavior in children and teenagers. That prompted the Food and Drug Administration to issue a warning on the risk in 2004. The agency later expanded that warning to include young adults up to age 25.
But the warning remains controversial, and more recent analyses have suggested that the benefits of treating anxiety and depression with SSRIs outweigh increased risks of suicidal behavior.
This latest study doesn't look at whether taking SSRIs increases the risk of suicide. Instead, it looks at whether different doses of the medications affect the risk of suicidal behavior.
"The design of the study was meant to really address the question, does dose matter?" Dr. Matthew Miller, an associate professor at the Harvard School of Public Health and lead author of the study, told Shots.
To find out, Miller and his colleagues looked at pharmacy benefits records for 162,625 people who had been diagnosed with depression and prescribed antidepressants for the first time from 1998 to 2010. They then sifted through those records and matched up people based on their risk factors for various health problems, so they were as similar as possible.
They found that people under age 25 who got a higher initial dose of antidepressants were twice as likely to try to harm themselves, while that wasn't true for people 25 and older.
That meant an additional one suicide attempt for every 150 people started with higher-dose therapy, the study found. The risk was especially high in the first three months of treatment.
"It certainly is one more piece of information that should make doctors reluctant to start younger patients on high doses," Miller says, "even if those doses are within the therapeutic range."
That's not saying that taking the average dose is safe, Miller notes, because the people taking an average dose had a higher suicide risk than the older people, too. "It doesn't give SSRIs a pass at all."
Although the researchers were careful to try to remove any influence from various risk factors, since this was an observational study, it leaves key questions unanswered.
That includes why higher doses would increase suicide risk; whether increasing dosage after a few months would also increase risk; or if switching drugs would be more effective and less risky than increasing the amount.
It also leaves open the question of the safest way to stop taking antidepressants. Other research has found that discontinuing antidepressants or changing the dosage can boost suicide risk.
And then there's the question of why doctors prescribe what they do. Almost 20 percent of people in the study were given an initial prescription for higher-dose antidepressants, even though prescribing guidelines don't recommend that.