D. Are There Contraindications to Opioid Therapy That Cannot Be Resolved?

OBJECTIVE

Avoid inappropriate or harmful therapy.

BACKGROUND

Although there are few absolute contraindications to the use of opioids in chronic pain, many factors must be considered prior to initiating therapy. The clinician must carefully weigh risks and benefits of chronic opioid therapy, and should discuss them with the patient and family/care giver where appropriate. Patients with relative contraindications pose a higher risk of legal and clinical problems.

RECOMMENDATIONS

1. Opioid therapy should not be used in the following situations (absolute contraindications):
• Allergy to opioid agents (may be resolved by switching agents)
• Co-administration of drug capable of inducing life-limiting drug-drug interaction
• Active diversion of controlled substances (providing the medication to someone for whom it was not intended)
2. Opioid therapy should be used only after careful consideration of the risks and benefits (relative contraindications):
• Acute psychiatric instability or high suicide risk
• History of intolerance, serious adverse effects, or lack of efficacy of opioid therapy
• Meets DSM-IV criteria for current substance use disorder (DSM IV, 1994)
• Inability to manage opioid therapy responsibly (e.g., cognitively impaired)
• Unwillingness or inability to comply with treatment plan
• Unwillingness to adjust at-risk activities resulting in serious re-injury
• Social instability
• Patient with sleep apnea not on CPAP
• Elderly patients
• COPD patients
3. Consider consultation with an appropriate specialist if legal or clinical problems indicate that more intensive care related to opioid management is indicated. A patient with substance use problem should be referred to a substance use specialty for concurrent treatment of substance use.

DISCUSSION

Absolute contraindications

1. Allergy to opioid agents
   
   Morphine causes the release of histamine, frequently resulting in itching, but this is not an allergic reaction. True allergy to opioid agents (e.g. anaphylaxis) is not common but does occur. Generally, allergy to one opioid agent does not mean the patient is allergic to other opioids; also switching to an agent in another opioid drug class may be effective. For example, if a patient has a hypersensitivity to a phenanthrene, then a diphenylheptane drug may be tried. (See table below.) When patients report an "allergy" to all but one agent (such as meperidine), the presence of a substance use disorder should be considered. Consultation with an allergist may be helpful to resolve these issues.

2. Co-administration of a drug capable of inducing life limiting drug-drug interaction
   
   Providers should carefully evaluate potential drug interactions prior to initiating opioid therapy, (such as MAOI with concurrent meperidine use, or propoxyphene and alcohol and other CNS depressants). (Note: meperidine is not recommended for chronic pain because of this potentially fatal drug interaction and the potential for accumulation of the neurotoxic metabolite, normeperidine, with regular dosing.)
   
3. Active diversion of controlled substances
   
   Diversion should be suspected when there are frequent requests for early refills, atypically large quantities are required, when purposeful misrepresentation of the pain disorder is suspected, or when a urine drug screen (UDS) is negative for the substance being prescribed, in the absence of withdrawal symptoms. Routine UDS often does not detect synthetic and semi-synthetic opioids (methadone, oxycodone, fentanyl, hydrocodone, meperidine or hydromorphone). Verified diversion is a crime and constitutes a strong contraindication to prescribing additional medications, and consultation with a pain specialist, psychiatrist, or addiction specialist may be warranted.

Relative contraindications

4. Acute psychiatric instability
   
   Current serious suicidality, severe depression, or unstable bipolar disorder or psychotic disorder precludes safe use of opioids, unless the patient is closely monitored and professional staff or family members administer the medication (Harden, 2002).
   
5. Intolerance, serious adverse effects or history of inadequate clinical response to opioids (lack of efficacy)
   
   Although generally well tolerated, opioids have potential adverse effects that may cause significant morbidity.
   
6. Meets DSM-IVR criteria for current substance use disorder (SUD) other than nicotine dependence
   
   Current substance abuse or dependence increases the risk of drug-drug interactions, addiction to prescribed opioids, and diversion. However, use of a substance, whether legal or illegal, does not in itself constitute a substance use disorder. A medical diagnosis of a SUD should be made according to the Diagnostic and Statistical Manual-Version IV, Revised (DSM-IV). A diagnosis of SUD requires that substance use is maladaptive and results in clinically significant impairment or distress. Chronic and appropriate use of prescribed opioids will cause cause physiologic dependence and may result in tolerance. However, appropriate use of opioids for chronic pain that results in improved function and quality of life does not constitute a SUD. The term "pseudoaddiction" describes prescription of an inadequate dose of opioids, leading to attempts by the patient to seek additional pain relief through additional medication. The proper response to pseudoaddiction is to adjust the dose of opioids to provide effective pain relief.
   
   It is not clear whether a history of a SUD in sustained remission (> 12 months) is predictive of increased risk for development of addiction in the context of opioid therapy. However, prudence dictates that the provider consider the stability of remission, including the patient's insight, participation in recovery activities such as self-help groups, and social support. Providers should consider consultation with an addiction specialist when the patient has a more recent history of a SUD, when remission is unstable, or for patients with a history of prior opioid addiction, intravenous drug use, or prescription drug abuse or dependence (Large & Schug, 1995; Becker et al., 2000).
   
   Substance Dependence (or addiction) refers to a condition characterized by a presentation of three or more of seven specific symptoms, defined in DSM-IV. Psychological dependence or drug addiction is different from physiologic dependence. Substance dependence requires a higher level of intervention and management than substance abuse.
   
7. Inability to manage opioid therapy responsibly
   
   Patients may repeatedly "lose" medication, may be unable or unwilling to store the medication in a safe place, or may repeatedly run short and ask for early refills, or obtain medication from more than one physician or pharmacy. The likelihood of these problems can be minimized by clearly specifying expectations prior to initiating therapy through the use of the written contract agreement (See Appendix C). Many patients respond to reminders and clear limit setting at the first instance, but repeated occurrence makes continuing therapy difficult. If a patient is cognitively impaired, assistance of a responsible caregiver may be required.
   
8. Unwillingness or inability to comply with reasonable treatment plan
   
   Treatment of chronic pain often requires a multidisciplinary approach (such as physical therapy, relaxation training, or psychiatric treatment), which requires active participation of the patient. Similarly, patients must make lifestyle changes to accommodate chronic pain. Repeated failure of the patient to follow through raises questions about the motivation of the patient and the appropriateness of continued opioid therapy. Patients must be counseled about this, and barriers to participation should be addressed. When this fails to result in improved participation, consideration must be given to discontinuing opioid therapy.
   
9. Social instability
   
   Patients living in chaotic or unsafe environments (e.g. homeless shelter, living with others who are using cocaine) should not receive opioids until social stability is achieved.