The number of methadone-related deaths of men in England and Wales rose by more than a third last year to its highest rate since 1997, figures have showed.
The 15-year high comes after studies found an increase in the drug's use by primary heroin users, possibly as a result of the heroin drought, the Office for National Statistics (ONS) said.
The number of women's deaths linked to any drug also rose, up 3% from 857 to 880 in 2011, while the number of women's deaths linked to illegal drugs also rose 3% from 402 in 2010 to 413 last year.
For men, a third of all drug deaths in 2011 were suicides, a 20% increase from 482 the previous year to 576 - the highest number since 2005, the ONS figures showed. For women, just under half of all drug deaths were suicides, up 7% from 391 in 2010 to 418 deaths last year.
Overall, the number of drug-related men's deaths - involving both legal and illegal drugs, prescription drugs and over-the-counter medicines - fell 6% to 1,772.
The number of men's deaths related to illegal drugs fell by 14% from 1,382 in 2010 to 1,192 last year. But the mortality rate from illegal drugs was still significantly higher in men (43.4 deaths per million of the population) than in women (14.4).
Some 486 deaths were linked to the heroin-substitute methadone, taking the mortality rate for men from the drug from 9.9 deaths per million of the population in 2010 to 13.5 - a 36% rise and the highest rate since 1997. The mortality rate for women from methadone was also up slightly to 4.3 deaths per million of the population.
"The increase in deaths involving methadone correlates with findings from the British Crime Survey showing the proportion of 16- to 59-year-olds using methadone in the last year increased significantly in 2010/11," the ONS said.
"In addition, the latest Druglink Street Drug Trends Survey found there had been an increase in the use of methadone (and other substances) by primary heroin users, possibly as a result of the heroin drought."
Heroin shortages in the UK began in 2010 due to a combination of severe flooding in Pakistan, exaggerated perceptions of a "poppy blight" in Afghanistan, and the actions of international and domestic law enforcement bodies.