Risk of overdose or respiratory depression is higher when patients Take other sedatives, such as benzodiazepines, muscle relaxants, gabapentin, and alcohol (risk is highest with benzodiazepines, which, when possible, should not be used with opioid therapy) Have comorbidities that affect hepatic or renal metabolism Risk factors for respiratory depression also include History of stroke, renal disease, heart failure, or chronic pulmonary disease Untreated or undertreated obstructive sleep apnea or chronic obstructive pulmonary disease (COPD) Substance use disorder Psychiatric disorders Concurrent use of some common psychoactive drugs Use of long-acting opioids, high-dose opioids (> 100 OMME), or methadone Modifiable risk factors for overdose or respiratory depression should be managed; strategies include Treating sleep apnea Advising patients not to drink alcohol when they take the opioid Not prescribing benzodiazepines with opioids when possible Not prescribing long-acting opioids when possible Prescribing methadone only if trained in its unique adverse effect profile Assessing the risk of overdose or serious opioid-induced respiratory depression using the Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression (RIOSORD) If patients are at increased risk of overdose or respiratory depression, practitioners should discuss the risk with them and their family members and should prescribe naloxone for them.