Hieu-Pham/cpgQA huggingface dataset:
Background information

The risk factors with the greatest impact on the development of opioid-related adverse events are the duration and dose of opioid analgesic use. Beyond duration and dose of OT, many factors increase the risk of adverse outcomes and must be considered prior to initiating or continuing OT (Box 1). Given the insufficient evidence of benefit for LOT, the clinician must carefully weigh harms and benefits and educate the patient as well as his or her family or caregiver prior to proceeding with treatment. As patient values and preferences may be impacted by other clinical considerations, some patients with one or more risk factors for adverse outcomes may differ with the clinician’s assessment that the risks of OT  outweigh the potential for modest short-term benefits. Thus, it is important to consider patients’ values and concerns, address misconceptions, express empathy, and fully explain to patients with one or more risk factors that they may not benefit from, and may even be harmed by, treatment with OT. Conditions that significantly increase the risk of adverse outcomes from LOT are listed below. Patients for whom LOT is initiated should be carefully monitored, and ongoing assessment of risk should be performed with vigilance for the development of additional risk factors and adverse outcomes (see Recommendations  7-9). Consider consultation with appropriate specialty care providers if there is uncertainty about whether the benefits of OT, such as improved function (e.g., return-to-work), outweigh the risks. 

Question: What should be done for patients for whom LOT is initiated?
Answer: should be carefully monitored, and ongoing assessment of risk should be performed with vigilance for the development of additional risk factors and adverse outcomes
Background information

The risk factors with the greatest impact on the development of opioid-related adverse events are the duration and dose of opioid analgesic use. Beyond duration and dose of OT, many factors increase the risk of adverse outcomes and must be considered prior to initiating or continuing OT (Box 1). Given the insufficient evidence of benefit for LOT, the clinician must carefully weigh harms and benefits and educate the patient as well as his or her family or caregiver prior to proceeding with treatment. As patient values and preferences may be impacted by other clinical considerations, some patients with one or more risk factors for adverse outcomes may differ with the clinician’s assessment that the risks of OT  outweigh the potential for modest short-term benefits. Thus, it is important to consider patients’ values and concerns, address misconceptions, express empathy, and fully explain to patients with one or more risk factors that they may not benefit from, and may even be harmed by, treatment with OT. Conditions that significantly increase the risk of adverse outcomes from LOT are listed below. Patients for whom LOT is initiated should be carefully monitored, and ongoing assessment of risk should be performed with vigilance for the development of additional risk factors and adverse outcomes (see Recommendations  7-9). Consider consultation with appropriate specialty care providers if there is uncertainty about whether the benefits of OT, such as improved function (e.g., return-to-work), outweigh the risks. 

Question: What to do if there is uncertainty about whether the benefits of OT, such as improved function (e.g., return-to-work), outweigh the risks?
Answer: Consider consultation with appropriate specialty care providers
Background information

Conditions that significantly increase the risk of adverse outcomes from LOT are Duration and dose of OT, Severe respiratory instability or sleep disordered breathing, Acute psychiatric instability or intermediate to high acute suicide risk, Mental health disorders, History of drug overdose, Under 30 years of age, Co-administration of a drug capable of inducing fatal drug-drug interactions, QTc interval >450 ms for using methadone, Evidence for or history of diversion of controlled substances, Intolerance, serious adverse effects, or a history of inadequate beneficial response to opioids, Impaired bowel motility unresponsive to therapy, Headache not responsive to other pain treatment modalities, Traumatic brain injury (TBI), True allergy to opioid agents.

Question: Which conditions significantly increase the risk of adverse outcomes from LOT?
Answer: Duration and dose of OT, Severe respiratory instability or sleep disordered breathing, Acute psychiatric instability or intermediate to high acute suicide risk, Mental health disorders, History of drug overdose, Under 30 years of age, Co-administration of a drug capable of inducing fatal drug-drug interactions, QTc interval >450 ms for using methadone, Evidence for or history of diversion of controlled substances, Intolerance, serious adverse effects, or a history of inadequate beneficial response to opioids, Impaired bowel motility unresponsive to therapy, Headache not responsive to other pain treatment modalities, Traumatic brain injury (TBI), True allergy to opioid agents
Background information

Duration and dose of OT: See Recommendation 2 for more guidance on duration of OT and Recommendations 10-12 for more guidance on dosing of OT. Severe respiratory instability or sleep disordered breathing: This would include any co-occurring condition that significantly affects respiratory rate or function such as chronic obstructive pulmonary disease (COPD), asthma, pneumonia, sleep apnea, or a neuromuscular condition (e.g., amyotrophic lateral sclerosis). Two large observational studies of patients with a  history of COPD and sleep apnea who were prescribed opioids showed a weak but positive association with opioid-related toxicity/overdose and overdose-related death.[58,59]

Question: What does include severe respiratory instability or sleep disordered breathing?
Answer: any co-occurring condition that significantly affects respiratory rate or function such as chronic obstructive pulmonary disease (COPD), asthma, pneumonia, sleep apnea, or a neuromuscular condition (e.g., amyotrophic lateral sclerosis)
Background information

Duration and dose of OT: See Recommendation 2 for more guidance on duration of OT and Recommendations 10-12 for more guidance on dosing of OT. Severe respiratory instability or sleep disordered breathing: This would include any co-occurring condition that significantly affects respiratory rate or function such as chronic obstructive pulmonary disease (COPD), asthma, pneumonia, sleep apnea, or a neuromuscular condition (e.g., amyotrophic lateral sclerosis). Two large observational studies of patients with a  history of COPD and sleep apnea who were prescribed opioids showed a weak but positive association with opioid-related toxicity/overdose and overdose-related death.[58,59]

Question: Who showed a weak but positive association with opioid-related toxicity/overdose and overdose-related death?
Answer: Two large observational studies of patients with a  history of COPD and sleep apnea who were prescribed opioids
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: What does preclude the safe use of self-administered LOT?
Answer: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: What was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids?
Answer: a  diagnosis of a mood disorder
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: In a study of patients on opioids, who had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder?
Answer: those with bipolar disorder
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: What are the odds of suicidal ideation within the past 12 months in those with bipolar disorder compared to those with no bipolar disorder?
Answer: 2.9 times
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: What are the odds of a lifetime suicide attempt in those with bipolar disorder compared to those with no bipolar disorder?
Answer: 3.2  times
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: Where can more information on suicidality be found?
Answer: the VA/DoD Suicide CPG
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: Where can more information on bipolar disorder be found?
Answer: the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG)
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: What was associated with depressed mood?
Answer: high dose chronic opioid therapy for pain
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]  

Question: Which treatment for chronic pain may have benefits in treating depression, PTSD, and in reducing suicide risk?
Answer: Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain
Background information

Current or history of SUD: For patients with untreated SUD, see Recommendation 4. For  patients with diagnosed OUD, see Recommendation 17. Frequent requests for early refills or atypically large quantities required to control pain can signal an emerging SUD as well as  diversion (see Evidence for or history of diversion of controlled substances). See the VA/DoD  SUD CPG.4 Depression or history of depression: Zedler et al. (2014) reported that among patients  being treated by the VHA system that received opioids, a history of depression was  significantly associated with opioid-related toxicity/overdose compared to no history of  depression.[58] LOT has been associated with worsening depressive symptoms.[63] See the  VA/DoD MDD CPG.5 PTSD: Seal et al. (2012) (n=15,676) noted that among patients on OT, a prevalence of self inflicted injuries was significantly higher among patients with a history of PTSD (with or  without other mental health diagnoses) as compared to patients with other (or no) mental  health diagnoses.[65] For more information, see the VA/DoD PTSD CPG.6 History of drug overdose: A history of overdose is a red flag and providers should proceed with  utmost caution when considering LOT for these patients. Under 30 years of age: See Recommendation 6. 

Question: What can signal an emerging SUD as well as  diversion?
Answer: Frequent requests for early refills or atypically large quantities required to control pain
Background information

Current or history of SUD: For patients with untreated SUD, see Recommendation 4. For  patients with diagnosed OUD, see Recommendation 17. Frequent requests for early refills or atypically large quantities required to control pain can signal an emerging SUD as well as  diversion (see Evidence for or history of diversion of controlled substances). See the VA/DoD  SUD CPG.4 Depression or history of depression: Zedler et al. (2014) reported that among patients  being treated by the VHA system that received opioids, a history of depression was  significantly associated with opioid-related toxicity/overdose compared to no history of  depression.[58] LOT has been associated with worsening depressive symptoms.[63] See the  VA/DoD MDD CPG.5 PTSD: Seal et al. (2012) (n=15,676) noted that among patients on OT, a prevalence of self inflicted injuries was significantly higher among patients with a history of PTSD (with or  without other mental health diagnoses) as compared to patients with other (or no) mental  health diagnoses.[65] For more information, see the VA/DoD PTSD CPG.6 History of drug overdose: A history of overdose is a red flag and providers should proceed with  utmost caution when considering LOT for these patients. Under 30 years of age: See Recommendation 6. 

Question: What can be signalled by frequent requests for early refills required to control pain?
Answer: an emerging SUD as well as  diversion