Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study

Abstract

BackgroundThe use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown.Methods and FindingsWe conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy.ConclusionsMen are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated.

Availability of naloxone in Canadian pharmacies:a population-based survey

“…7,14,18,40 This may relate to a perceived stigma among people with an opioid use disorder or the perception that patients receiving high-dose opioids for chronic pain are not at risk of overdose. The cost of naloxone may also be a limiting factor.…”

“…There is a clear dose-dependent risk of opioidrelated death, 1,3,22 with 3.8% of men and 2.2% of women receiving greater than 200 mg of morphine (or equivalent) per day eventually dying of opioid-related causes. 18 There are tens of thousands of such patients in Canada. As health care professionals with regular, direct patient contact, pharmacists are uniquely positioned to facilitate access to an extremely safe and potentially life-saving antidote for patients receiving prescription opioids, particularly at high doses.…”

Patterns and trends in long-term opioid use for non-cancer pain in British Columbia, 2005–2012

“…Median [interquartile range, IQR] daily dose during the episode of long-term use was 4 [3-5] ME for occasional users, 8 [5][6][7][8][9][10][11]] ME for regular users, 17 [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] ME for chronic users and 79 [33-197] ME for every-day users.…”

Transitional Pain Medicine: novel pharmacological treatments for the management of moderate to severe postsurgical pain

“…High-dose opioid use in this context is closely linked with increased risk of mortality. [11,12] Novel strategies to reduce postsurgical pain: the development of a TPS to address a gap in the treatment of complex postsurgical pain patients…”