The CDC report focuses on prescription opioids like Vicodin and OxyContin and their generic forms, methadone, and a powerful newer drug called Opana, or oxymorphone.
"These are dangerous medications and they should be reserved for situations like severe cancer pain," Frieden said. He added that there has been no documented increase in pain in the U.S. public that would explain the boom in painkiller prescriptions in the last 10 or 15 years.
Some experts said the increase in prescriptions can be traced to pharmaceutical marketing campaigns.
CDC researchers reviewed death certificates, which are sometimes incomplete. In only a fraction of cases were specific drugs identified. Sometimes a combination of drugs was involved in deaths, like painkillers taken with tranquilizers.
It was not always clear which deaths were accidental overdoses and which were suicides. But CDC officials think more than 70 percent were unintentional.
One striking finding: The greatest increases in drug overdose deaths were in women ages 45 through 54, and 55 through 64. The rate for each of those groups more than tripled between 1999 and 2010.
In 2010, overdose deaths in those two groups of middle-aged women added up to about 7,400 -- or nearly half the female total, according to CDC statistics.
It's an age group in which more women are dealing with chronic pain and seeking help for it, some experts suggested.
Many of these women probably were introduced to painkillers through a doctor's prescriptions for real pain, such as persistent aches in the lower back or other parts of the body. Then some no doubt became addicted, said Dr. Andrew Kolodny, a psychiatrist who specializes in addiction at Maimonides Medical Center in New York City.
There aren't "two distinct populations of people being helped by opioid painkillers and addicts being harmed. There's overlap," said Kolodny, president of a 700-member organization named Physicians for Responsible Opioid Prescribing.