Suicide rates inched up in nearly every U.S. state from 1999 through 2016, according to a new government report released Thursday.

More than half of suicides in 2015 in a subgroup of 27 states were among people with no known mental health condition, the Centers for Disease Control and Prevention found. Suicide is rarely caused by any single factor, health officials said, but information from coroners’ reports suggest many of the deaths followed relationship problems, substance use and financial crises.

Prevention efforts, often focused on mental health, could be broadened to focus on people undergoing life stresses like job losses or divorces, the CDC’s Dr. Anne Schuchat said in a media briefing.

“Suicide is more than a mental health issue,” Schuchat said. “We don’t think we can just leave this to the mental health system to manage.”

Suicide is the 10th leading cause of death and one of just three leading causes that are on the rise. The others are Alzheimer’s disease and drug overdoses.

There were nearly 45,000 suicides in 2016. Middle-aged adults—ages 45 to 64—had the largest rate increase, rising to 19.2 per 100,000 in 2016 from 13.2 per 100,000 in 1999.

The report said people without known mental health problems were more likely to die by firearms than those with known mental health problems.

Family members or friends concerned about someone who is struggling can ask directly about suicide and remove firearms or any other means the person is considering from the home, said Jennifer Stuber, director of Forefront Suicide Prevention at the University of Washington in Seattle.

Prevention efforts are best done when “people can get help solving the underlying drivers of the problems causing them to feel hopeless and despair,” Stuber said.

The CDC report comes at a time of heightened attention to the issue with the suicide this week of designer Kate Spade. The designer’s husband, Andy Spade, has said she suffered from depression and anxiety for many years.

Overall, the rate rose to 15.4 per 100,000 in 2014-2016 from 12.3 per 100,000 in 1999-2001. Rates ranged from 6.9 per 100,000 in the District of Columbia to 29.2 per 100,000 in Montana.

Twenty-five states saw percentage rate increases of more than 30 percent over the 17 years.

The overall data came from coded death certificate records. The information on contributing factors reflect what family and friends told coroners and police in a subgroup of states participating in the CDC’s National Violent Death Reporting System. In the one-year analysis of 27 states, opioids were found in 31 percent of the 3,003 suicides involving drug overdoses.

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