"Historically, suicide rates tend to correlate with business cycles, with higher rates observed during times of economic hardship," the report noted.
The suicide rate among middle-aged people increased 28 percent between 1999 and 2010, from 13.7 to 17.6 suicides per 100,000 people.
The CDC said the trend is most pronounced among Native Americans (65 percent), whites (40 percent) and people in their 50s (48-49 percent). The middle-aged cohort includes people ages 35 to 64.
Officials warned that current suicide prevention efforts tend to address young people and the elderly, not adults facing the challenges of middle age.
The baby boom generation is already associated with higher rates of suicide and will need help as it confronts job loss, caregiving and declining health, the CDC said.
Rates of suicide among young people and those older than 65 did not change substantially in the last 15 years, according to the report.