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Prescription opioid use disorder: A complex clinical challenge
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You’ve been treating Mr. H, a 54-year-old factory worker and tobacco user, for depression that developed after a work-related back injury and subsequent disability. His depression has had a fair response to an antidepressant. He also has been maintained on chronic opioids (morphine and oxycodone/acetaminophen) for 18 months by his primary care physician (PCP). At the end of your appointment, he asks you for a refill of the opioids because he “ran out” early because of increased night pain and resultant insomnia and “stress.” He clarifies he has asked for early refills before from his PCP, but lately he has been denied. Because you “seem to listen to me more,” he asks for your help. How should you manage Mr. H?
Opioids are among the most commonly misused prescription drugs in the United States.1 In 2008, poisoning was the leading cause of death from injury in the United States; roughly 90% of poisonings resulted from drug exposure, and >40% of these drug poisonings were from prescription opioids.2 The Centers for Disease Control and Prevention estimates that the number of emergency department (ED) visits for nonmedical use of opioids increased 111% between 2004 and 2008, from 144,600 to 305,900 visits.3 The highest number of visits were for use of oxycodone, hydrocodone, and methadone.3
Increased prescribing of opioids and overdose deaths attributable to prescribed opioids have raised concern among physicians about how to effectively treat pain as well as prevent, recognize, and manage aberrant medication-taking behaviors (AMTBs). Psychiatrists are well-positioned to screen and manage their own patients for prescription opioid use disorder (POUD) or collaborate with opioid prescribers to accomplish the same.
Clarifying terminology
Terminology used to describe POUD and related conditions often is poorly defined or loosely applied. Because emotions often enter discussions between patients and physicians about problems related to opioid therapy, nonstigmatizing and more objective terminology is needed, and clinicians are working toward standardizing this. Relevant terms are defined in Table 1.4
The DSM-5 Substance Use Disorders Work Group has proposed using the term opioid use disorder (OUD) to replace the term opioid dependence.5 The hope is that removing the word “dependence” from the diagnostic term will reduce confusion between “dependence” due to expected physical dependence (tolerance, withdrawal) on medically prescribed opioids vs true addiction (currently defined as “opioid dependence” in DSM-IV-TR). This Work Group also has proposed combining opioid abuse and opioid dependence criteria into a single diagnosis of OUD, and adding “craving” to the criteria. For the complete proposed criteria, see www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460.These changes are still under review. In this article, we use the term POUD.
Table 1
Terminology related to prescription opioid use disorder
| Term | Definition |
|---|---|
| Chronic paina | Pain that extends beyond the expected period for healing (6 months), initiated by tissue damage, but perpetrated by the interaction of physiologic, affective, and environmental factors |
| Chronic nonmalignant paina | Chronic pain associated with diverse diagnoses and syndromes that are not terminal but affect the patient’s function |
| Appropriate usea | Taking a prescription as prescribed, and only for the condition indicated |
| Misusea | Taking a prescription for a reason or at a dose or frequency other than for which it was prescribed; this may or may not reflect POUD |
| Drug-seeking behaviors | Patient behaviors directed toward obtaining controlled substances, driven not by amelioration of the condition for which the medication was indicated but rather by other maladaptive gains; this may or may not reflect POUD |
| Chemical coping | Taking a controlled substance medication to relieve psychological problems (eg, to relieve low mood, anxiety, insomnia) and for reasons other than the purpose for which it was prescribed; this may or may not reflect POUD |
| Aberrant medication-taking behaviorsa | Taking a controlled substance medication in a manner that is not prescribed; causes for this may include:
|
| Pseudoaddiction | An iatrogenic syndrome of “addiction-like” behaviors in which the patient seeks opioids to relieve pain—such as seeking different doctors, self-adjusting the opioid dose, early refills of opioids, etc.—rather than to achieve pleasure or other nonpain-related effect. At times mistaken for true addiction, these behaviors tend to resolve and function improves once analgesia is better addressed |
| a These terms and definitions are adapted from reference 4. The remaining terms and definitions were developed by the authors POUD: prescription opioid use disorder | |
POUD and chronic pain
The incidence of POUD during opioid therapy for pain is unknown.6 Some researchers have suggested it may be as low as 0.2%,7 while others estimate that rates of POUD in patients with chronic pain may be similar to those in the general population: 3% to 16%.8 When applying the proposed DSM-5 criteria to patients receiving long-term opioid therapy for noncancer pain, the lifetime prevalence of POUD may be as high as 35%.9
Prescribers may be contributing to POUD. Roughly 76% of opioids used for nonmedical purposes were prescribed to someone else, 20% were prescribed to the user, and 4% came from other sources.1 Strategies to reduce POUD risk may be underused. In a retrospective cohort study of 1,612 patient electronic medical records from 8 primary care clinics that managed patients with long-term opioids for chronic noncancer pain (average prescribing duration of 2 years duration, ≥3 monthly prescriptions in 6 months), researchers evaluated how often prescribers used 3 risk reduction practices:
- urine drug tests
- regular office visits (≥1 every 6 months and within 30 days of changing opioid treatment)
- restricted early refills (≤1 opioid refill more than a week early).10
Risk factors for opioid misuse included age 1 early refill. Researchers found that even for high-risk patients, these strategies were used infrequently. Less than one-quarter of patients with ≥3 risk factors ever had a drug test, and those at increased risk were more likely to receive >1 early refill but no more likely to have more frequent visits. Issues such as patient entitlement, lack of physician education, and time constraints may explain why these strategies are not used more often.11
No one procedure or set of variables is sufficient to identify chronic pain patients who may be at risk for POUD. However, a history of drug or alcohol use disorders may be a significant risk factor.12,13
Few tools have been developed to help identify those at risk of AMTBs or POUD, and all have limitations.4,14 Recommended self-report measures include the Current Opioid Misuse Measure and the Opioid Risk Tool.15 A review of studies in which these kinds of tools were developed revealed limited evidence for their use; most studies had methodological shortcomings, did not use standardized AMTB criteria, and provided little assessment of whether these tools changed clinician behaviors or improved patient outcomes.16
Evaluating AMTBs
Although diagnosing POUD in pain patients receiving chronic opioids can be challenging, assessing for AMTBs typically is helpful. Once AMTBs are identified, they can be examined to determine what drives their expression (Table 14 and Table 217). However, often it is easier to identify AMTBs than to interpret their origins; as much as 30% to 50% of patients who complain of chronic pain may have primary substance dependence to sedatives, opioids, or both.11
Table 2
Aberrant medication-taking behaviors and POUD risk
| Behaviors more suggestive of POUD |
|---|
| Deterioration in function (work, social) |
| Illegal activities (selling medication, forging prescriptions, buying from non-medical sources) |
| Altering the route of administration (snorting, injecting) |
| Multiple episodes of ‘lost’ or ‘stolen’ prescriptions |
| Resistance to change therapy despite negative outcomes |
| Refusal to comply with toxicology testing |
| Concurrent, active abuse of alcohol, illegal drugs |
| Use of multiple physicians or pharmacies to obtain the prescription |
| Behaviors less suggestive of POUD |
| Complaints for more medication |
| Medication hoarding |
| Requesting specific pain medications |
| Openly acquiring similar medications from other providers |
| Occasional unsanctioned dose escalation |
| Nonadherence to other recommendations for pain therapy |
| POUD: prescription opioid use disorder Source: Reference 17 |
Although AMTBs are common among chronic nonmalignant pain patients,18,19 how often AMTBs reflect underlying POUD is uncertain.7 It is critical to interpret AMTBs with a balance of caution and care: “react therapeutically, not punitively.”20 Categorizing a patient’s AMTB as more or less likely to support a POUD diagnosis can be helpful, but is not conclusive (Table 2).17 Clinical correlation often is required. No single AMTB alone is indicative of POUD. When evaluating AMTBs, the treating provider should use a nonjudgmental stance, and consider obtaining collateral data from people who can provide differing perspectives of the patient’s behaviors, such as other clinicians, significant others, family, etc. (a release of information from the patient may be required). Another source of collateral data is prescription monitoring databases. These databases typically are state-based and provide electronic access to prescription information, allowing you to search for patterns—ie, use of multiple prescribers or pharmacies, undisclosed prescriptions, etc. Interest in establishing a single, federal database has been increasing, but striking a balance between carefully monitoring for AMTBs and protecting privacy remains unresolved.
DSM-IV-TR diagnostic criteria for opioid dependence21 can be challenging to interpret in patients who are prescribed opioids for pain (Table 3
).6 To clarify interpretation, the Liaison Committee on Pain and Addiction of the American Society of Addiction Medicine (ASAM) has provided an outline of possible indicators of addiction in pain patients (Table 4).6 This was a consensus statement from the American Pain Society, the American Academy of Pain Medicine, and ASAM.
Assessment is primarily clinical and requires an awareness of appropriate terminology, an index of clinical suspicion, and expertise teasing apart pain, addiction, and pseudoaddiction. In our experience, it is helpful to ask a chronic pain patient whom you suspect might have POUD, “Have you ever used your prescribed opioids for reasons other than improving function or reducing pain, such as for getting a ‘high,’ managing stress, escaping from problems, etc.?” An affirmative response suggests an underlying problem with use of prescribed opioids, indicating a need for more careful questioning to determine if AMTBs or POUD coexist with chronic pain.
Drug testing can help determine if a patient is taking opioids that are not prescribed—as well as illicit drugs or alcohol—and confirm the presence of those that are prescribed. Toxicology screening should include opioids typically screened for (eg, morphine, codeine, heroin) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and hydrocodone and synthetics such as fentanyl).
Table 3
Identifying addiction in pain patients: Limitations of DSM-IV-TR
| DSM-IV-TR substance dependence criteria | Challenges in using criterion to diagnose prescription opioid use disorder |
|---|---|
| Tolerance | Expected with prolonged opioid compliance |
| Physical dependence, withdrawal | Expected with prolonged opioid compliance |
| Use of larger amounts or longer than initially intended | Emergence of pain may demand increased dose or prolonged use |
| Multiple failed attempts to cut down or control | Emergence of pain may deter dose reduction or cessation |
| Time spent finding, using, or recovering | Difficulty finding adequate pain treatment may increase time spent pursuing analgesics. However, time spent recovering from overuse may suggest addiction |
| Given up or reduced important activities | Valid criteria—engaging in activities is expected to increase, not decline, with effective pain treatment |
| Continued use despite knowledge of negative consequences | Valid criteria—no harm is anticipated from analgesic opioid use for pain (see Table 4) |
| Source: Adapted from reference 6 | |
Table 4
Possible indicators of addiction in pain patients
| ASAM-APS-AAPM behavioral criteria | Examples of specific behaviors in opioid therapy for pain |
|---|---|
| Impaired control over opioid use | Patient requests early refills, frequently reports loss or theft of medication. Withdrawal noted at follow-up appointments despite having an adequate quantity of medication prescribed |
| Continued use despite harm from opioids | Patient exhibits declining function, opioid intoxication, persistent oversedation from opioids |
| Preoccupation with opioids | Patient ignores non-opioid interventions for pain, makes recurrent requests for opioid dose escalation (or complains of increasing pain) despite absence of disease progression or despite opioid dose increase by provider |
| AAPM: American Academy of Pain Medicine; APS: American Pain Society; ASAM: American Society of Addiction Medicine Source: Adapted from reference 6 | |
Helping POUD patients
Goals of treatment include establishing a therapeutic alliance, educating patients about POUD, reducing relapse risk, and optimizing overall health (including pain and physical function). The ASAM Patient Placement Criteria22 provide guidance regarding level-of-care decisions. Treatment ideally includes a combination of education about POUD and its relationship to chronic pain, pharmacotherapy, psychotherapy—such as motivational enhancement therapy, 12-step facilitation therapy, cognitive-behavioral therapy, and relapse prevention—and referral to self-help groups such as Narcotics Anonymous or Pills Anonymous. Importantly, if pain is genuine, it requires treatment.
Pharmacotherapy. Methadone is recommended as the standard of care for OUD by the National Institutes of Health. Methadone is a full opioid agonist that decreases illicit opioid use, mortality, and related problems and requires highly structured treatment approaches under federal and state regulation. POUD patients may have higher rates of methadone maintenance treatment retention than heroin-dependent patients.23 Published trials of buprenorphine for OUD have shown good treatment retention and reduction in illicit drug use and adverse events.24 Buprenorphine also decreases mortality among OUD patients.
The first large-scale, randomized clinical trial of buprenorphine specifically for POUD included 653 treatment-seeking outpatients.25 This study was designed to approximate clinical practice and included buprenorphine/naloxone, recommended abstinence, and self-help; one-half of participants received intensive addiction counseling. POUD patients were most likely to reduce prescription opioid misuse during buprenorphine/naloxone treatment. If tapered off buprenorphine/naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome was high. Moreover, opioid dependence counseling did not seem to afford any difference in outcomes. However, despite clinical effectiveness, over the last decade only 19% of patients admitted primarily for OUD treatment (other than heroin) were planned to be offered buprenorphine or methadone.26
A Cochrane review of oral naltrexone for OUD found that the drug was no better than placebo but concluded that available evidence does not allow an adequate evaluation.27 Opioid antagonists may be of value to patients who do not want to take agonists or partial agonists. Extended-release naltrexone also is available to treat OUD.
See the Box below that details steps the FDA and others have taken to prevent POUD and Table 5 for precautions to incorporate when prescribing opioids long-term.
The FDA has moved toward a risk evaluation and mitigation strategy (REMS) for opioids prescribed for pain that requires clinicians to receive training and certification in prescribing opioids for pain as well as identifying and reducing the risk for prescription opioid use disorder (POUD).a In 2011, the Obama administration developed an action plan to better address prescription drug abuse that required several federal agencies to develop programs and policies to address this growing problem; this plan was updated for 2012 (the complete National Drug Control Strategy 2012 is available at www.whitehouse.gov/sites/default/files/ondcp/2012_ndcs.pdf). The American Society of Addiction Medicine has issued a public policy statement that supports the federal approach and outlines other means to reduce POUD.b
Some pain specialists recommend requiring patients to sign an Opioid Pain Management Agreement that includes an “exit strategy” before the first opioid prescription is written. These agreements incorporate elements of “universal precautions” to take when prescribing opioids long term.c,d Although not well-studied, prescribing agreements may help educate patients and providers on how to interact in the management of pain with opioids in a way that is objective and empathic, and may reduce POUD risk.
References
- U.S. Department of Health and Human Services. U.S. Food and Drug Administration. Opioid drugs and risk evaluation and mitigation strategies (REMS). http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm163647.htm. Updated April 5, 2012. Accessed June 28, 2012.
- American Society of Addiction Medicine. Measures to counteract prescription drug diversion, misuse and addiction. http://www.asam.org/advocacy/find-a-policy-statement/view-policy-statement/public-policy-statements/2012/01/26/measures-to-counteract-prescription-drug-diversion-misuse-and-addiction. Published January 25, 2012. Accessed June 20, 2012.
- Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):107-112.
- Gourlay DL, Heit HA. Universal precautions revisited: managing the inherited pain patient. Pain Med. 2009; 10(suppl 2):S115-S123.
Table 5
Universal precautions with chronic opioid management
| Goals of therapy: partial pain relief and improvement in physical, emotional, and/or social functioning |
| Requirement for a single prescribing provider or treatment team |
| Limitation on dose and number of prescribed medications |
| Prohibition of changing dosage without discussion with the provider first |
| Monitoring patient adherence; discuss the use of ‘pill counts’ |
| Prohibition of use with alcohol, other sedating medications, or illegal drugs without discussion with the provider |
| Agreement not to drive or operate heavy machinery until abatement of medication-related drowsiness |
| Responsibility to keep medication safe and secure |
| Prohibition of selling, lending, sharing, or giving medication to others |
| Limitations on refills—only by appointment, in person, and no extra refills for running out early |
| Compliance with all components of overall treatment plan (including consultations and referrals) |
| Biological testing to screen for drugs of abuse or alcohol as well as to confirm the presence of prescribed opioids |
| Adverse effects and safety issues, such as the risk of physical dependence and addiction behaviors |
| The option of sharing information with family members and other providers, as necessary, with the patient’s consent |
| Need for periodic reevaluation of treatment |
| Reasons for stopping opioid therapy |
| Consequences of nonadherence with the treatment agreement |
| Source: Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):107-112. |
CASE CONTINUED: A closer evaluation
After expressing your appreciation for Mr. H’s kind words and empathy for his chronic pain, you redirect him to his PCP. You ask him to sign a release of information so you and his other clinicians can coordinate his care. When discussing Mr. H with his PCP, you learn the patient has made limited requests for early refills and dose escalation primarily in relation to inadequate pain control and function, has genuine pain pathology, and is greatly distressed over his inability to work. No other AMTBs are present, and a check of the state prescribing database reveals that Mr. H did receive a small quantity of opioids from an ED on 1 occasion.
You and Mr. H’s PCP agree this is “pseudo-addiction” but want to watch Mr. H more closely and look for ways to coordinate his care. The PCP agrees to implement a prescribing agreement, start drug testing (including for the prescribed opioids), and reassess maximizing Mr. H’s function and pain management while you address his combined pain, depression, insomnia, and tobacco use.
Related Resources
- Ries RK, Fiellin D, Miller SC, et al, eds. Principles of addiction medicine. 4th ed. Hagerstown, MD: Lippincott Williams & Wilkins; 2009.
- Department of Veterans Affairs. Department of Defense. VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. Appendix C: sample opioid pain care agreement. http://www.healthquality.va.gov/COT_312_Full-er.pdf. Published May 2010. Accessed June 21, 2012.
- Weaver M, Schnoll S. Addiction issues in prescribing opioids for chronic non-malignant pain. J Addiction Med. 2007;1(1):2-10.
- Weaver M, Heit HA, Savage S, et al. Clinical case discussion: chronic pain management. J Addiction Med. 2007;1(1):11-14.
Drug Brand Names
- Buprenorphine • Subutex
- Buprenorphine/naloxone • Suboxone
- Codeine • Tylenol with codeine, others
- Fentanyl • Duragesic, Actiq
- Hydrocodone • Lortab, Vicodin, others
- Methadone • Dolophine, Methadose
- Morphine • Roxanol
- Naltrexone extended-release • Vivitrol
- Oxycodone • OxyContin, Roxicodone
Disclosures
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Frankowski’s time toward this project was provided by the American Board of Addiction Medicine-accredited Cincinnati VA Addiction Medicine Research Fellowship, affiliated with the CeTREAD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs.
Acknowledgement
The authors thank Catherine Constance and Sandra Mason at the Cincinnati VA Medical Center for their administrative assistance.
1. U.S. Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Office of Applied Studies. Results from the 2009 national survey on drug use and health: volume I. http://www.samhsa.gov/data/NSDUH/2k9NSDUH/2k9Results.htm. Accessed June 20, 2012.
2. Warner M, Chen LH, Makuc DM, et al. Drug poisoning deaths in the United States, 1980-2008. http://www.cdc.gov/nchs/data/databriefs/db81.htm. Published December 2011. Accessed June 20, 2012.
3. Centers for Disease Control and Prevention (CDC). Emergency department visits involving nonmedical use of selected prescription drugs - United States 2004-2008. MMWR Morb Mortal Wkly Rep. 2010;59(23):705-709.
4. Weaver M, Schnoll S. Addiction issues in prescribing opioids for chronic nonmalignant pain. J Addict Med. 2007;1(1):2-10.
5. American Psychiatric Association. R 19 opioid use disorder. http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460. Updated April 30 2012. Accessed June 20, 2012.
6. Savage SR, Horvath R. Opioid therapy of pain. In: Ries RK Fiellin DA, Miller SC, et al, eds. Principles of addiction medicine. 4th ed. Hagerstown, MD: Lippincott Williams & Wilkins; 2009:1329-1351.
7. Fishbain DA, Cole B, Lewis J, et al. What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? A structured evidence-based review. Pain Med. 2008;9(4):444-459.
8. Gourlay DL, Heit HA. Pain and addiction: managing risk through comprehensive care. J Addict Dis. 2008;27(3):23-30.
9. Boscarino JA, Rukstalis MR, Hoffman SN, et al. Prevalence of prescription opioid-use disorder among chronic pain patients: comparison of the DSM-5 vs. DSM-4 diagnostic criteria. J Addict Dis. 2011;30(3):185-194.
10. Starrels JL, Becker WC, Weiner MG, et al. Low use of opioid risk reduction strategies in primary care even for high risk patients with chronic pain. J Gen Intern Med. 2011;26(9):958-964.
11. Miller NS. Failure of enforcement controlled substance laws in health policy for prescribing opiate medications: a painful assessment of morbidity and mortality. Am J Ther. 2006;13(6):527-533.
12. Turk DC, Swanson KS, Gatchel RJ. Predicting opioid misuse by chronic pain patients: a systematic review and literature synthesis. Clin J Pain. 2008;24(6):497-508.
13. Miller NS, Greenfeld A. Patient characteristics and risks factors for development of dependence on hydrocodone and oxycodone. Am J Ther. 2004;11(1):26-32.
14. Butler SF, Budman SH, Fernandez KC, et al. Cross-validation of a Screener to Predict Opioid Misuse in Chronic Pain Patients (SOAPP-R). J Addict Med. 2009;3(2):66-73.
15. Passik SD, Kirsh KL, Casper D. Addiction-related assessment tools and pain management: instruments for screening treatment planning, and monitoring compliance. Pain Med. 2008;9(suppl 2):S145-S166.
16. Chou R, Fanciullo GJ, Fine PG, et al. Opioids for chronic noncancer pain: prediction and identification of aberrant drug-related behaviors: a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. J Pain. 2009;10(2):131-146.
17. Alford DP, Liebschutz J, Jackson A, et al. Prescription drug abuse: an introduction. http://www.drugabuse.gov/sites/default/files/prescription-drug-abuse-alt.pdf. Published November 8, 2009. Accessed June 20, 2012.
18. Passik SD, Kirsh KL, Whitcomb L, et al. Monitoring outcomes during long-term opioid therapy for noncancer pain: results with the Pain Assessment and Documentation Tool. J Opioid Manag. 2005;1(5):257-266.
19. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005;6(6):432-442.
20. Passik SD. Pain management misstatements: ceiling effects red and yellow flags. Pain Med. 2006;7(1):76-77.
21. Diagnostic and statistical manual of mental disorders 4th ed text rev. Washington DC: American Psychiatric Association; 2000.
22. Mee-Lee D, Shulman GD, Fishman MJ, et al. eds. ASAM patient placement criteria for the treatment of substance-related disorders. 2nd ed. Chevy Chase, MD: American Society of Addiction Medicine, Inc.; 2001.
23. Banta-Green CJ, Maynard C, Koepsell TD, et al. Retention in methadone maintenance drug treatment for prescription-type opioid primary users compared to heroin users. Addiction. 2009;104(5):775-783.
24. Moore BA, Fiellin DA, Barry DT, et al. Primary care office-based buprenorphine treatment: comparison of heroin and prescription opioid dependent patients. J Gen Intern Med. 2007;22(4):527-530.
25. Weiss RD, Potter JS, Fiellin DA, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry. 2011;68(12):1238-1246.
26. U.S. Department of Health and Human Services (HHS). Substance Abuse and Mental Health Services Administration (SAMHSA). Office of Applied Studies. Treatment Episode Data Set (TEDS). 1998 - 2008. National Admissions to Substance Abuse Treatment Services, DASIS Series: S-50, HHS Publication No. (SMA) 09-4471. Rockville, MD; 2010.
27. Minozzi S, Amato L, Vecchi S, et al. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database Syst Rev. 2011;(4):CD001333.-
Discuss this article at www.facebook.com/CurrentPsychiatry
You’ve been treating Mr. H, a 54-year-old factory worker and tobacco user, for depression that developed after a work-related back injury and subsequent disability. His depression has had a fair response to an antidepressant. He also has been maintained on chronic opioids (morphine and oxycodone/acetaminophen) for 18 months by his primary care physician (PCP). At the end of your appointment, he asks you for a refill of the opioids because he “ran out” early because of increased night pain and resultant insomnia and “stress.” He clarifies he has asked for early refills before from his PCP, but lately he has been denied. Because you “seem to listen to me more,” he asks for your help. How should you manage Mr. H?
Opioids are among the most commonly misused prescription drugs in the United States.1 In 2008, poisoning was the leading cause of death from injury in the United States; roughly 90% of poisonings resulted from drug exposure, and >40% of these drug poisonings were from prescription opioids.2 The Centers for Disease Control and Prevention estimates that the number of emergency department (ED) visits for nonmedical use of opioids increased 111% between 2004 and 2008, from 144,600 to 305,900 visits.3 The highest number of visits were for use of oxycodone, hydrocodone, and methadone.3
Increased prescribing of opioids and overdose deaths attributable to prescribed opioids have raised concern among physicians about how to effectively treat pain as well as prevent, recognize, and manage aberrant medication-taking behaviors (AMTBs). Psychiatrists are well-positioned to screen and manage their own patients for prescription opioid use disorder (POUD) or collaborate with opioid prescribers to accomplish the same.
Clarifying terminology
Terminology used to describe POUD and related conditions often is poorly defined or loosely applied. Because emotions often enter discussions between patients and physicians about problems related to opioid therapy, nonstigmatizing and more objective terminology is needed, and clinicians are working toward standardizing this. Relevant terms are defined in Table 1.4
The DSM-5 Substance Use Disorders Work Group has proposed using the term opioid use disorder (OUD) to replace the term opioid dependence.5 The hope is that removing the word “dependence” from the diagnostic term will reduce confusion between “dependence” due to expected physical dependence (tolerance, withdrawal) on medically prescribed opioids vs true addiction (currently defined as “opioid dependence” in DSM-IV-TR). This Work Group also has proposed combining opioid abuse and opioid dependence criteria into a single diagnosis of OUD, and adding “craving” to the criteria. For the complete proposed criteria, see www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460.These changes are still under review. In this article, we use the term POUD.
Table 1
Terminology related to prescription opioid use disorder
| Term | Definition |
|---|---|
| Chronic paina | Pain that extends beyond the expected period for healing (6 months), initiated by tissue damage, but perpetrated by the interaction of physiologic, affective, and environmental factors |
| Chronic nonmalignant paina | Chronic pain associated with diverse diagnoses and syndromes that are not terminal but affect the patient’s function |
| Appropriate usea | Taking a prescription as prescribed, and only for the condition indicated |
| Misusea | Taking a prescription for a reason or at a dose or frequency other than for which it was prescribed; this may or may not reflect POUD |
| Drug-seeking behaviors | Patient behaviors directed toward obtaining controlled substances, driven not by amelioration of the condition for which the medication was indicated but rather by other maladaptive gains; this may or may not reflect POUD |
| Chemical coping | Taking a controlled substance medication to relieve psychological problems (eg, to relieve low mood, anxiety, insomnia) and for reasons other than the purpose for which it was prescribed; this may or may not reflect POUD |
| Aberrant medication-taking behaviorsa | Taking a controlled substance medication in a manner that is not prescribed; causes for this may include:
|
| Pseudoaddiction | An iatrogenic syndrome of “addiction-like” behaviors in which the patient seeks opioids to relieve pain—such as seeking different doctors, self-adjusting the opioid dose, early refills of opioids, etc.—rather than to achieve pleasure or other nonpain-related effect. At times mistaken for true addiction, these behaviors tend to resolve and function improves once analgesia is better addressed |
| a These terms and definitions are adapted from reference 4. The remaining terms and definitions were developed by the authors POUD: prescription opioid use disorder | |
POUD and chronic pain
The incidence of POUD during opioid therapy for pain is unknown.6 Some researchers have suggested it may be as low as 0.2%,7 while others estimate that rates of POUD in patients with chronic pain may be similar to those in the general population: 3% to 16%.8 When applying the proposed DSM-5 criteria to patients receiving long-term opioid therapy for noncancer pain, the lifetime prevalence of POUD may be as high as 35%.9
Prescribers may be contributing to POUD. Roughly 76% of opioids used for nonmedical purposes were prescribed to someone else, 20% were prescribed to the user, and 4% came from other sources.1 Strategies to reduce POUD risk may be underused. In a retrospective cohort study of 1,612 patient electronic medical records from 8 primary care clinics that managed patients with long-term opioids for chronic noncancer pain (average prescribing duration of 2 years duration, ≥3 monthly prescriptions in 6 months), researchers evaluated how often prescribers used 3 risk reduction practices:
- urine drug tests
- regular office visits (≥1 every 6 months and within 30 days of changing opioid treatment)
- restricted early refills (≤1 opioid refill more than a week early).10
Risk factors for opioid misuse included age 1 early refill. Researchers found that even for high-risk patients, these strategies were used infrequently. Less than one-quarter of patients with ≥3 risk factors ever had a drug test, and those at increased risk were more likely to receive >1 early refill but no more likely to have more frequent visits. Issues such as patient entitlement, lack of physician education, and time constraints may explain why these strategies are not used more often.11
No one procedure or set of variables is sufficient to identify chronic pain patients who may be at risk for POUD. However, a history of drug or alcohol use disorders may be a significant risk factor.12,13
Few tools have been developed to help identify those at risk of AMTBs or POUD, and all have limitations.4,14 Recommended self-report measures include the Current Opioid Misuse Measure and the Opioid Risk Tool.15 A review of studies in which these kinds of tools were developed revealed limited evidence for their use; most studies had methodological shortcomings, did not use standardized AMTB criteria, and provided little assessment of whether these tools changed clinician behaviors or improved patient outcomes.16
Evaluating AMTBs
Although diagnosing POUD in pain patients receiving chronic opioids can be challenging, assessing for AMTBs typically is helpful. Once AMTBs are identified, they can be examined to determine what drives their expression (Table 14 and Table 217). However, often it is easier to identify AMTBs than to interpret their origins; as much as 30% to 50% of patients who complain of chronic pain may have primary substance dependence to sedatives, opioids, or both.11
Table 2
Aberrant medication-taking behaviors and POUD risk
| Behaviors more suggestive of POUD |
|---|
| Deterioration in function (work, social) |
| Illegal activities (selling medication, forging prescriptions, buying from non-medical sources) |
| Altering the route of administration (snorting, injecting) |
| Multiple episodes of ‘lost’ or ‘stolen’ prescriptions |
| Resistance to change therapy despite negative outcomes |
| Refusal to comply with toxicology testing |
| Concurrent, active abuse of alcohol, illegal drugs |
| Use of multiple physicians or pharmacies to obtain the prescription |
| Behaviors less suggestive of POUD |
| Complaints for more medication |
| Medication hoarding |
| Requesting specific pain medications |
| Openly acquiring similar medications from other providers |
| Occasional unsanctioned dose escalation |
| Nonadherence to other recommendations for pain therapy |
| POUD: prescription opioid use disorder Source: Reference 17 |
Although AMTBs are common among chronic nonmalignant pain patients,18,19 how often AMTBs reflect underlying POUD is uncertain.7 It is critical to interpret AMTBs with a balance of caution and care: “react therapeutically, not punitively.”20 Categorizing a patient’s AMTB as more or less likely to support a POUD diagnosis can be helpful, but is not conclusive (Table 2).17 Clinical correlation often is required. No single AMTB alone is indicative of POUD. When evaluating AMTBs, the treating provider should use a nonjudgmental stance, and consider obtaining collateral data from people who can provide differing perspectives of the patient’s behaviors, such as other clinicians, significant others, family, etc. (a release of information from the patient may be required). Another source of collateral data is prescription monitoring databases. These databases typically are state-based and provide electronic access to prescription information, allowing you to search for patterns—ie, use of multiple prescribers or pharmacies, undisclosed prescriptions, etc. Interest in establishing a single, federal database has been increasing, but striking a balance between carefully monitoring for AMTBs and protecting privacy remains unresolved.
DSM-IV-TR diagnostic criteria for opioid dependence21 can be challenging to interpret in patients who are prescribed opioids for pain (Table 3
).6 To clarify interpretation, the Liaison Committee on Pain and Addiction of the American Society of Addiction Medicine (ASAM) has provided an outline of possible indicators of addiction in pain patients (Table 4).6 This was a consensus statement from the American Pain Society, the American Academy of Pain Medicine, and ASAM.
Assessment is primarily clinical and requires an awareness of appropriate terminology, an index of clinical suspicion, and expertise teasing apart pain, addiction, and pseudoaddiction. In our experience, it is helpful to ask a chronic pain patient whom you suspect might have POUD, “Have you ever used your prescribed opioids for reasons other than improving function or reducing pain, such as for getting a ‘high,’ managing stress, escaping from problems, etc.?” An affirmative response suggests an underlying problem with use of prescribed opioids, indicating a need for more careful questioning to determine if AMTBs or POUD coexist with chronic pain.
Drug testing can help determine if a patient is taking opioids that are not prescribed—as well as illicit drugs or alcohol—and confirm the presence of those that are prescribed. Toxicology screening should include opioids typically screened for (eg, morphine, codeine, heroin) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and hydrocodone and synthetics such as fentanyl).
Table 3
Identifying addiction in pain patients: Limitations of DSM-IV-TR
| DSM-IV-TR substance dependence criteria | Challenges in using criterion to diagnose prescription opioid use disorder |
|---|---|
| Tolerance | Expected with prolonged opioid compliance |
| Physical dependence, withdrawal | Expected with prolonged opioid compliance |
| Use of larger amounts or longer than initially intended | Emergence of pain may demand increased dose or prolonged use |
| Multiple failed attempts to cut down or control | Emergence of pain may deter dose reduction or cessation |
| Time spent finding, using, or recovering | Difficulty finding adequate pain treatment may increase time spent pursuing analgesics. However, time spent recovering from overuse may suggest addiction |
| Given up or reduced important activities | Valid criteria—engaging in activities is expected to increase, not decline, with effective pain treatment |
| Continued use despite knowledge of negative consequences | Valid criteria—no harm is anticipated from analgesic opioid use for pain (see Table 4) |
| Source: Adapted from reference 6 | |
Table 4
Possible indicators of addiction in pain patients
| ASAM-APS-AAPM behavioral criteria | Examples of specific behaviors in opioid therapy for pain |
|---|---|
| Impaired control over opioid use | Patient requests early refills, frequently reports loss or theft of medication. Withdrawal noted at follow-up appointments despite having an adequate quantity of medication prescribed |
| Continued use despite harm from opioids | Patient exhibits declining function, opioid intoxication, persistent oversedation from opioids |
| Preoccupation with opioids | Patient ignores non-opioid interventions for pain, makes recurrent requests for opioid dose escalation (or complains of increasing pain) despite absence of disease progression or despite opioid dose increase by provider |
| AAPM: American Academy of Pain Medicine; APS: American Pain Society; ASAM: American Society of Addiction Medicine Source: Adapted from reference 6 | |
Helping POUD patients
Goals of treatment include establishing a therapeutic alliance, educating patients about POUD, reducing relapse risk, and optimizing overall health (including pain and physical function). The ASAM Patient Placement Criteria22 provide guidance regarding level-of-care decisions. Treatment ideally includes a combination of education about POUD and its relationship to chronic pain, pharmacotherapy, psychotherapy—such as motivational enhancement therapy, 12-step facilitation therapy, cognitive-behavioral therapy, and relapse prevention—and referral to self-help groups such as Narcotics Anonymous or Pills Anonymous. Importantly, if pain is genuine, it requires treatment.
Pharmacotherapy. Methadone is recommended as the standard of care for OUD by the National Institutes of Health. Methadone is a full opioid agonist that decreases illicit opioid use, mortality, and related problems and requires highly structured treatment approaches under federal and state regulation. POUD patients may have higher rates of methadone maintenance treatment retention than heroin-dependent patients.23 Published trials of buprenorphine for OUD have shown good treatment retention and reduction in illicit drug use and adverse events.24 Buprenorphine also decreases mortality among OUD patients.
The first large-scale, randomized clinical trial of buprenorphine specifically for POUD included 653 treatment-seeking outpatients.25 This study was designed to approximate clinical practice and included buprenorphine/naloxone, recommended abstinence, and self-help; one-half of participants received intensive addiction counseling. POUD patients were most likely to reduce prescription opioid misuse during buprenorphine/naloxone treatment. If tapered off buprenorphine/naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome was high. Moreover, opioid dependence counseling did not seem to afford any difference in outcomes. However, despite clinical effectiveness, over the last decade only 19% of patients admitted primarily for OUD treatment (other than heroin) were planned to be offered buprenorphine or methadone.26
A Cochrane review of oral naltrexone for OUD found that the drug was no better than placebo but concluded that available evidence does not allow an adequate evaluation.27 Opioid antagonists may be of value to patients who do not want to take agonists or partial agonists. Extended-release naltrexone also is available to treat OUD.
See the Box below that details steps the FDA and others have taken to prevent POUD and Table 5 for precautions to incorporate when prescribing opioids long-term.
The FDA has moved toward a risk evaluation and mitigation strategy (REMS) for opioids prescribed for pain that requires clinicians to receive training and certification in prescribing opioids for pain as well as identifying and reducing the risk for prescription opioid use disorder (POUD).a In 2011, the Obama administration developed an action plan to better address prescription drug abuse that required several federal agencies to develop programs and policies to address this growing problem; this plan was updated for 2012 (the complete National Drug Control Strategy 2012 is available at www.whitehouse.gov/sites/default/files/ondcp/2012_ndcs.pdf). The American Society of Addiction Medicine has issued a public policy statement that supports the federal approach and outlines other means to reduce POUD.b
Some pain specialists recommend requiring patients to sign an Opioid Pain Management Agreement that includes an “exit strategy” before the first opioid prescription is written. These agreements incorporate elements of “universal precautions” to take when prescribing opioids long term.c,d Although not well-studied, prescribing agreements may help educate patients and providers on how to interact in the management of pain with opioids in a way that is objective and empathic, and may reduce POUD risk.
References
- U.S. Department of Health and Human Services. U.S. Food and Drug Administration. Opioid drugs and risk evaluation and mitigation strategies (REMS). http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm163647.htm. Updated April 5, 2012. Accessed June 28, 2012.
- American Society of Addiction Medicine. Measures to counteract prescription drug diversion, misuse and addiction. http://www.asam.org/advocacy/find-a-policy-statement/view-policy-statement/public-policy-statements/2012/01/26/measures-to-counteract-prescription-drug-diversion-misuse-and-addiction. Published January 25, 2012. Accessed June 20, 2012.
- Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):107-112.
- Gourlay DL, Heit HA. Universal precautions revisited: managing the inherited pain patient. Pain Med. 2009; 10(suppl 2):S115-S123.
Table 5
Universal precautions with chronic opioid management
| Goals of therapy: partial pain relief and improvement in physical, emotional, and/or social functioning |
| Requirement for a single prescribing provider or treatment team |
| Limitation on dose and number of prescribed medications |
| Prohibition of changing dosage without discussion with the provider first |
| Monitoring patient adherence; discuss the use of ‘pill counts’ |
| Prohibition of use with alcohol, other sedating medications, or illegal drugs without discussion with the provider |
| Agreement not to drive or operate heavy machinery until abatement of medication-related drowsiness |
| Responsibility to keep medication safe and secure |
| Prohibition of selling, lending, sharing, or giving medication to others |
| Limitations on refills—only by appointment, in person, and no extra refills for running out early |
| Compliance with all components of overall treatment plan (including consultations and referrals) |
| Biological testing to screen for drugs of abuse or alcohol as well as to confirm the presence of prescribed opioids |
| Adverse effects and safety issues, such as the risk of physical dependence and addiction behaviors |
| The option of sharing information with family members and other providers, as necessary, with the patient’s consent |
| Need for periodic reevaluation of treatment |
| Reasons for stopping opioid therapy |
| Consequences of nonadherence with the treatment agreement |
| Source: Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):107-112. |
CASE CONTINUED: A closer evaluation
After expressing your appreciation for Mr. H’s kind words and empathy for his chronic pain, you redirect him to his PCP. You ask him to sign a release of information so you and his other clinicians can coordinate his care. When discussing Mr. H with his PCP, you learn the patient has made limited requests for early refills and dose escalation primarily in relation to inadequate pain control and function, has genuine pain pathology, and is greatly distressed over his inability to work. No other AMTBs are present, and a check of the state prescribing database reveals that Mr. H did receive a small quantity of opioids from an ED on 1 occasion.
You and Mr. H’s PCP agree this is “pseudo-addiction” but want to watch Mr. H more closely and look for ways to coordinate his care. The PCP agrees to implement a prescribing agreement, start drug testing (including for the prescribed opioids), and reassess maximizing Mr. H’s function and pain management while you address his combined pain, depression, insomnia, and tobacco use.
Related Resources
- Ries RK, Fiellin D, Miller SC, et al, eds. Principles of addiction medicine. 4th ed. Hagerstown, MD: Lippincott Williams & Wilkins; 2009.
- Department of Veterans Affairs. Department of Defense. VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. Appendix C: sample opioid pain care agreement. http://www.healthquality.va.gov/COT_312_Full-er.pdf. Published May 2010. Accessed June 21, 2012.
- Weaver M, Schnoll S. Addiction issues in prescribing opioids for chronic non-malignant pain. J Addiction Med. 2007;1(1):2-10.
- Weaver M, Heit HA, Savage S, et al. Clinical case discussion: chronic pain management. J Addiction Med. 2007;1(1):11-14.
Drug Brand Names
- Buprenorphine • Subutex
- Buprenorphine/naloxone • Suboxone
- Codeine • Tylenol with codeine, others
- Fentanyl • Duragesic, Actiq
- Hydrocodone • Lortab, Vicodin, others
- Methadone • Dolophine, Methadose
- Morphine • Roxanol
- Naltrexone extended-release • Vivitrol
- Oxycodone • OxyContin, Roxicodone
Disclosures
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Frankowski’s time toward this project was provided by the American Board of Addiction Medicine-accredited Cincinnati VA Addiction Medicine Research Fellowship, affiliated with the CeTREAD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs.
Acknowledgement
The authors thank Catherine Constance and Sandra Mason at the Cincinnati VA Medical Center for their administrative assistance.
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You’ve been treating Mr. H, a 54-year-old factory worker and tobacco user, for depression that developed after a work-related back injury and subsequent disability. His depression has had a fair response to an antidepressant. He also has been maintained on chronic opioids (morphine and oxycodone/acetaminophen) for 18 months by his primary care physician (PCP). At the end of your appointment, he asks you for a refill of the opioids because he “ran out” early because of increased night pain and resultant insomnia and “stress.” He clarifies he has asked for early refills before from his PCP, but lately he has been denied. Because you “seem to listen to me more,” he asks for your help. How should you manage Mr. H?
Opioids are among the most commonly misused prescription drugs in the United States.1 In 2008, poisoning was the leading cause of death from injury in the United States; roughly 90% of poisonings resulted from drug exposure, and >40% of these drug poisonings were from prescription opioids.2 The Centers for Disease Control and Prevention estimates that the number of emergency department (ED) visits for nonmedical use of opioids increased 111% between 2004 and 2008, from 144,600 to 305,900 visits.3 The highest number of visits were for use of oxycodone, hydrocodone, and methadone.3
Increased prescribing of opioids and overdose deaths attributable to prescribed opioids have raised concern among physicians about how to effectively treat pain as well as prevent, recognize, and manage aberrant medication-taking behaviors (AMTBs). Psychiatrists are well-positioned to screen and manage their own patients for prescription opioid use disorder (POUD) or collaborate with opioid prescribers to accomplish the same.
Clarifying terminology
Terminology used to describe POUD and related conditions often is poorly defined or loosely applied. Because emotions often enter discussions between patients and physicians about problems related to opioid therapy, nonstigmatizing and more objective terminology is needed, and clinicians are working toward standardizing this. Relevant terms are defined in Table 1.4
The DSM-5 Substance Use Disorders Work Group has proposed using the term opioid use disorder (OUD) to replace the term opioid dependence.5 The hope is that removing the word “dependence” from the diagnostic term will reduce confusion between “dependence” due to expected physical dependence (tolerance, withdrawal) on medically prescribed opioids vs true addiction (currently defined as “opioid dependence” in DSM-IV-TR). This Work Group also has proposed combining opioid abuse and opioid dependence criteria into a single diagnosis of OUD, and adding “craving” to the criteria. For the complete proposed criteria, see www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460.These changes are still under review. In this article, we use the term POUD.
Table 1
Terminology related to prescription opioid use disorder
| Term | Definition |
|---|---|
| Chronic paina | Pain that extends beyond the expected period for healing (6 months), initiated by tissue damage, but perpetrated by the interaction of physiologic, affective, and environmental factors |
| Chronic nonmalignant paina | Chronic pain associated with diverse diagnoses and syndromes that are not terminal but affect the patient’s function |
| Appropriate usea | Taking a prescription as prescribed, and only for the condition indicated |
| Misusea | Taking a prescription for a reason or at a dose or frequency other than for which it was prescribed; this may or may not reflect POUD |
| Drug-seeking behaviors | Patient behaviors directed toward obtaining controlled substances, driven not by amelioration of the condition for which the medication was indicated but rather by other maladaptive gains; this may or may not reflect POUD |
| Chemical coping | Taking a controlled substance medication to relieve psychological problems (eg, to relieve low mood, anxiety, insomnia) and for reasons other than the purpose for which it was prescribed; this may or may not reflect POUD |
| Aberrant medication-taking behaviorsa | Taking a controlled substance medication in a manner that is not prescribed; causes for this may include:
|
| Pseudoaddiction | An iatrogenic syndrome of “addiction-like” behaviors in which the patient seeks opioids to relieve pain—such as seeking different doctors, self-adjusting the opioid dose, early refills of opioids, etc.—rather than to achieve pleasure or other nonpain-related effect. At times mistaken for true addiction, these behaviors tend to resolve and function improves once analgesia is better addressed |
| a These terms and definitions are adapted from reference 4. The remaining terms and definitions were developed by the authors POUD: prescription opioid use disorder | |
POUD and chronic pain
The incidence of POUD during opioid therapy for pain is unknown.6 Some researchers have suggested it may be as low as 0.2%,7 while others estimate that rates of POUD in patients with chronic pain may be similar to those in the general population: 3% to 16%.8 When applying the proposed DSM-5 criteria to patients receiving long-term opioid therapy for noncancer pain, the lifetime prevalence of POUD may be as high as 35%.9
Prescribers may be contributing to POUD. Roughly 76% of opioids used for nonmedical purposes were prescribed to someone else, 20% were prescribed to the user, and 4% came from other sources.1 Strategies to reduce POUD risk may be underused. In a retrospective cohort study of 1,612 patient electronic medical records from 8 primary care clinics that managed patients with long-term opioids for chronic noncancer pain (average prescribing duration of 2 years duration, ≥3 monthly prescriptions in 6 months), researchers evaluated how often prescribers used 3 risk reduction practices:
- urine drug tests
- regular office visits (≥1 every 6 months and within 30 days of changing opioid treatment)
- restricted early refills (≤1 opioid refill more than a week early).10
Risk factors for opioid misuse included age 1 early refill. Researchers found that even for high-risk patients, these strategies were used infrequently. Less than one-quarter of patients with ≥3 risk factors ever had a drug test, and those at increased risk were more likely to receive >1 early refill but no more likely to have more frequent visits. Issues such as patient entitlement, lack of physician education, and time constraints may explain why these strategies are not used more often.11
No one procedure or set of variables is sufficient to identify chronic pain patients who may be at risk for POUD. However, a history of drug or alcohol use disorders may be a significant risk factor.12,13
Few tools have been developed to help identify those at risk of AMTBs or POUD, and all have limitations.4,14 Recommended self-report measures include the Current Opioid Misuse Measure and the Opioid Risk Tool.15 A review of studies in which these kinds of tools were developed revealed limited evidence for their use; most studies had methodological shortcomings, did not use standardized AMTB criteria, and provided little assessment of whether these tools changed clinician behaviors or improved patient outcomes.16
Evaluating AMTBs
Although diagnosing POUD in pain patients receiving chronic opioids can be challenging, assessing for AMTBs typically is helpful. Once AMTBs are identified, they can be examined to determine what drives their expression (Table 14 and Table 217). However, often it is easier to identify AMTBs than to interpret their origins; as much as 30% to 50% of patients who complain of chronic pain may have primary substance dependence to sedatives, opioids, or both.11
Table 2
Aberrant medication-taking behaviors and POUD risk
| Behaviors more suggestive of POUD |
|---|
| Deterioration in function (work, social) |
| Illegal activities (selling medication, forging prescriptions, buying from non-medical sources) |
| Altering the route of administration (snorting, injecting) |
| Multiple episodes of ‘lost’ or ‘stolen’ prescriptions |
| Resistance to change therapy despite negative outcomes |
| Refusal to comply with toxicology testing |
| Concurrent, active abuse of alcohol, illegal drugs |
| Use of multiple physicians or pharmacies to obtain the prescription |
| Behaviors less suggestive of POUD |
| Complaints for more medication |
| Medication hoarding |
| Requesting specific pain medications |
| Openly acquiring similar medications from other providers |
| Occasional unsanctioned dose escalation |
| Nonadherence to other recommendations for pain therapy |
| POUD: prescription opioid use disorder Source: Reference 17 |
Although AMTBs are common among chronic nonmalignant pain patients,18,19 how often AMTBs reflect underlying POUD is uncertain.7 It is critical to interpret AMTBs with a balance of caution and care: “react therapeutically, not punitively.”20 Categorizing a patient’s AMTB as more or less likely to support a POUD diagnosis can be helpful, but is not conclusive (Table 2).17 Clinical correlation often is required. No single AMTB alone is indicative of POUD. When evaluating AMTBs, the treating provider should use a nonjudgmental stance, and consider obtaining collateral data from people who can provide differing perspectives of the patient’s behaviors, such as other clinicians, significant others, family, etc. (a release of information from the patient may be required). Another source of collateral data is prescription monitoring databases. These databases typically are state-based and provide electronic access to prescription information, allowing you to search for patterns—ie, use of multiple prescribers or pharmacies, undisclosed prescriptions, etc. Interest in establishing a single, federal database has been increasing, but striking a balance between carefully monitoring for AMTBs and protecting privacy remains unresolved.
DSM-IV-TR diagnostic criteria for opioid dependence21 can be challenging to interpret in patients who are prescribed opioids for pain (Table 3
).6 To clarify interpretation, the Liaison Committee on Pain and Addiction of the American Society of Addiction Medicine (ASAM) has provided an outline of possible indicators of addiction in pain patients (Table 4).6 This was a consensus statement from the American Pain Society, the American Academy of Pain Medicine, and ASAM.
Assessment is primarily clinical and requires an awareness of appropriate terminology, an index of clinical suspicion, and expertise teasing apart pain, addiction, and pseudoaddiction. In our experience, it is helpful to ask a chronic pain patient whom you suspect might have POUD, “Have you ever used your prescribed opioids for reasons other than improving function or reducing pain, such as for getting a ‘high,’ managing stress, escaping from problems, etc.?” An affirmative response suggests an underlying problem with use of prescribed opioids, indicating a need for more careful questioning to determine if AMTBs or POUD coexist with chronic pain.
Drug testing can help determine if a patient is taking opioids that are not prescribed—as well as illicit drugs or alcohol—and confirm the presence of those that are prescribed. Toxicology screening should include opioids typically screened for (eg, morphine, codeine, heroin) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and hydrocodone and synthetics such as fentanyl).
Table 3
Identifying addiction in pain patients: Limitations of DSM-IV-TR
| DSM-IV-TR substance dependence criteria | Challenges in using criterion to diagnose prescription opioid use disorder |
|---|---|
| Tolerance | Expected with prolonged opioid compliance |
| Physical dependence, withdrawal | Expected with prolonged opioid compliance |
| Use of larger amounts or longer than initially intended | Emergence of pain may demand increased dose or prolonged use |
| Multiple failed attempts to cut down or control | Emergence of pain may deter dose reduction or cessation |
| Time spent finding, using, or recovering | Difficulty finding adequate pain treatment may increase time spent pursuing analgesics. However, time spent recovering from overuse may suggest addiction |
| Given up or reduced important activities | Valid criteria—engaging in activities is expected to increase, not decline, with effective pain treatment |
| Continued use despite knowledge of negative consequences | Valid criteria—no harm is anticipated from analgesic opioid use for pain (see Table 4) |
| Source: Adapted from reference 6 | |
Table 4
Possible indicators of addiction in pain patients
| ASAM-APS-AAPM behavioral criteria | Examples of specific behaviors in opioid therapy for pain |
|---|---|
| Impaired control over opioid use | Patient requests early refills, frequently reports loss or theft of medication. Withdrawal noted at follow-up appointments despite having an adequate quantity of medication prescribed |
| Continued use despite harm from opioids | Patient exhibits declining function, opioid intoxication, persistent oversedation from opioids |
| Preoccupation with opioids | Patient ignores non-opioid interventions for pain, makes recurrent requests for opioid dose escalation (or complains of increasing pain) despite absence of disease progression or despite opioid dose increase by provider |
| AAPM: American Academy of Pain Medicine; APS: American Pain Society; ASAM: American Society of Addiction Medicine Source: Adapted from reference 6 | |
Helping POUD patients
Goals of treatment include establishing a therapeutic alliance, educating patients about POUD, reducing relapse risk, and optimizing overall health (including pain and physical function). The ASAM Patient Placement Criteria22 provide guidance regarding level-of-care decisions. Treatment ideally includes a combination of education about POUD and its relationship to chronic pain, pharmacotherapy, psychotherapy—such as motivational enhancement therapy, 12-step facilitation therapy, cognitive-behavioral therapy, and relapse prevention—and referral to self-help groups such as Narcotics Anonymous or Pills Anonymous. Importantly, if pain is genuine, it requires treatment.
Pharmacotherapy. Methadone is recommended as the standard of care for OUD by the National Institutes of Health. Methadone is a full opioid agonist that decreases illicit opioid use, mortality, and related problems and requires highly structured treatment approaches under federal and state regulation. POUD patients may have higher rates of methadone maintenance treatment retention than heroin-dependent patients.23 Published trials of buprenorphine for OUD have shown good treatment retention and reduction in illicit drug use and adverse events.24 Buprenorphine also decreases mortality among OUD patients.
The first large-scale, randomized clinical trial of buprenorphine specifically for POUD included 653 treatment-seeking outpatients.25 This study was designed to approximate clinical practice and included buprenorphine/naloxone, recommended abstinence, and self-help; one-half of participants received intensive addiction counseling. POUD patients were most likely to reduce prescription opioid misuse during buprenorphine/naloxone treatment. If tapered off buprenorphine/naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome was high. Moreover, opioid dependence counseling did not seem to afford any difference in outcomes. However, despite clinical effectiveness, over the last decade only 19% of patients admitted primarily for OUD treatment (other than heroin) were planned to be offered buprenorphine or methadone.26
A Cochrane review of oral naltrexone for OUD found that the drug was no better than placebo but concluded that available evidence does not allow an adequate evaluation.27 Opioid antagonists may be of value to patients who do not want to take agonists or partial agonists. Extended-release naltrexone also is available to treat OUD.
See the Box below that details steps the FDA and others have taken to prevent POUD and Table 5 for precautions to incorporate when prescribing opioids long-term.
The FDA has moved toward a risk evaluation and mitigation strategy (REMS) for opioids prescribed for pain that requires clinicians to receive training and certification in prescribing opioids for pain as well as identifying and reducing the risk for prescription opioid use disorder (POUD).a In 2011, the Obama administration developed an action plan to better address prescription drug abuse that required several federal agencies to develop programs and policies to address this growing problem; this plan was updated for 2012 (the complete National Drug Control Strategy 2012 is available at www.whitehouse.gov/sites/default/files/ondcp/2012_ndcs.pdf). The American Society of Addiction Medicine has issued a public policy statement that supports the federal approach and outlines other means to reduce POUD.b
Some pain specialists recommend requiring patients to sign an Opioid Pain Management Agreement that includes an “exit strategy” before the first opioid prescription is written. These agreements incorporate elements of “universal precautions” to take when prescribing opioids long term.c,d Although not well-studied, prescribing agreements may help educate patients and providers on how to interact in the management of pain with opioids in a way that is objective and empathic, and may reduce POUD risk.
References
- U.S. Department of Health and Human Services. U.S. Food and Drug Administration. Opioid drugs and risk evaluation and mitigation strategies (REMS). http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm163647.htm. Updated April 5, 2012. Accessed June 28, 2012.
- American Society of Addiction Medicine. Measures to counteract prescription drug diversion, misuse and addiction. http://www.asam.org/advocacy/find-a-policy-statement/view-policy-statement/public-policy-statements/2012/01/26/measures-to-counteract-prescription-drug-diversion-misuse-and-addiction. Published January 25, 2012. Accessed June 20, 2012.
- Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):107-112.
- Gourlay DL, Heit HA. Universal precautions revisited: managing the inherited pain patient. Pain Med. 2009; 10(suppl 2):S115-S123.
Table 5
Universal precautions with chronic opioid management
| Goals of therapy: partial pain relief and improvement in physical, emotional, and/or social functioning |
| Requirement for a single prescribing provider or treatment team |
| Limitation on dose and number of prescribed medications |
| Prohibition of changing dosage without discussion with the provider first |
| Monitoring patient adherence; discuss the use of ‘pill counts’ |
| Prohibition of use with alcohol, other sedating medications, or illegal drugs without discussion with the provider |
| Agreement not to drive or operate heavy machinery until abatement of medication-related drowsiness |
| Responsibility to keep medication safe and secure |
| Prohibition of selling, lending, sharing, or giving medication to others |
| Limitations on refills—only by appointment, in person, and no extra refills for running out early |
| Compliance with all components of overall treatment plan (including consultations and referrals) |
| Biological testing to screen for drugs of abuse or alcohol as well as to confirm the presence of prescribed opioids |
| Adverse effects and safety issues, such as the risk of physical dependence and addiction behaviors |
| The option of sharing information with family members and other providers, as necessary, with the patient’s consent |
| Need for periodic reevaluation of treatment |
| Reasons for stopping opioid therapy |
| Consequences of nonadherence with the treatment agreement |
| Source: Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):107-112. |
CASE CONTINUED: A closer evaluation
After expressing your appreciation for Mr. H’s kind words and empathy for his chronic pain, you redirect him to his PCP. You ask him to sign a release of information so you and his other clinicians can coordinate his care. When discussing Mr. H with his PCP, you learn the patient has made limited requests for early refills and dose escalation primarily in relation to inadequate pain control and function, has genuine pain pathology, and is greatly distressed over his inability to work. No other AMTBs are present, and a check of the state prescribing database reveals that Mr. H did receive a small quantity of opioids from an ED on 1 occasion.
You and Mr. H’s PCP agree this is “pseudo-addiction” but want to watch Mr. H more closely and look for ways to coordinate his care. The PCP agrees to implement a prescribing agreement, start drug testing (including for the prescribed opioids), and reassess maximizing Mr. H’s function and pain management while you address his combined pain, depression, insomnia, and tobacco use.
Related Resources
- Ries RK, Fiellin D, Miller SC, et al, eds. Principles of addiction medicine. 4th ed. Hagerstown, MD: Lippincott Williams & Wilkins; 2009.
- Department of Veterans Affairs. Department of Defense. VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. Appendix C: sample opioid pain care agreement. http://www.healthquality.va.gov/COT_312_Full-er.pdf. Published May 2010. Accessed June 21, 2012.
- Weaver M, Schnoll S. Addiction issues in prescribing opioids for chronic non-malignant pain. J Addiction Med. 2007;1(1):2-10.
- Weaver M, Heit HA, Savage S, et al. Clinical case discussion: chronic pain management. J Addiction Med. 2007;1(1):11-14.
Drug Brand Names
- Buprenorphine • Subutex
- Buprenorphine/naloxone • Suboxone
- Codeine • Tylenol with codeine, others
- Fentanyl • Duragesic, Actiq
- Hydrocodone • Lortab, Vicodin, others
- Methadone • Dolophine, Methadose
- Morphine • Roxanol
- Naltrexone extended-release • Vivitrol
- Oxycodone • OxyContin, Roxicodone
Disclosures
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Frankowski’s time toward this project was provided by the American Board of Addiction Medicine-accredited Cincinnati VA Addiction Medicine Research Fellowship, affiliated with the CeTREAD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs.
Acknowledgement
The authors thank Catherine Constance and Sandra Mason at the Cincinnati VA Medical Center for their administrative assistance.
1. U.S. Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Office of Applied Studies. Results from the 2009 national survey on drug use and health: volume I. http://www.samhsa.gov/data/NSDUH/2k9NSDUH/2k9Results.htm. Accessed June 20, 2012.
2. Warner M, Chen LH, Makuc DM, et al. Drug poisoning deaths in the United States, 1980-2008. http://www.cdc.gov/nchs/data/databriefs/db81.htm. Published December 2011. Accessed June 20, 2012.
3. Centers for Disease Control and Prevention (CDC). Emergency department visits involving nonmedical use of selected prescription drugs - United States 2004-2008. MMWR Morb Mortal Wkly Rep. 2010;59(23):705-709.
4. Weaver M, Schnoll S. Addiction issues in prescribing opioids for chronic nonmalignant pain. J Addict Med. 2007;1(1):2-10.
5. American Psychiatric Association. R 19 opioid use disorder. http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460. Updated April 30 2012. Accessed June 20, 2012.
6. Savage SR, Horvath R. Opioid therapy of pain. In: Ries RK Fiellin DA, Miller SC, et al, eds. Principles of addiction medicine. 4th ed. Hagerstown, MD: Lippincott Williams & Wilkins; 2009:1329-1351.
7. Fishbain DA, Cole B, Lewis J, et al. What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? A structured evidence-based review. Pain Med. 2008;9(4):444-459.
8. Gourlay DL, Heit HA. Pain and addiction: managing risk through comprehensive care. J Addict Dis. 2008;27(3):23-30.
9. Boscarino JA, Rukstalis MR, Hoffman SN, et al. Prevalence of prescription opioid-use disorder among chronic pain patients: comparison of the DSM-5 vs. DSM-4 diagnostic criteria. J Addict Dis. 2011;30(3):185-194.
10. Starrels JL, Becker WC, Weiner MG, et al. Low use of opioid risk reduction strategies in primary care even for high risk patients with chronic pain. J Gen Intern Med. 2011;26(9):958-964.
11. Miller NS. Failure of enforcement controlled substance laws in health policy for prescribing opiate medications: a painful assessment of morbidity and mortality. Am J Ther. 2006;13(6):527-533.
12. Turk DC, Swanson KS, Gatchel RJ. Predicting opioid misuse by chronic pain patients: a systematic review and literature synthesis. Clin J Pain. 2008;24(6):497-508.
13. Miller NS, Greenfeld A. Patient characteristics and risks factors for development of dependence on hydrocodone and oxycodone. Am J Ther. 2004;11(1):26-32.
14. Butler SF, Budman SH, Fernandez KC, et al. Cross-validation of a Screener to Predict Opioid Misuse in Chronic Pain Patients (SOAPP-R). J Addict Med. 2009;3(2):66-73.
15. Passik SD, Kirsh KL, Casper D. Addiction-related assessment tools and pain management: instruments for screening treatment planning, and monitoring compliance. Pain Med. 2008;9(suppl 2):S145-S166.
16. Chou R, Fanciullo GJ, Fine PG, et al. Opioids for chronic noncancer pain: prediction and identification of aberrant drug-related behaviors: a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. J Pain. 2009;10(2):131-146.
17. Alford DP, Liebschutz J, Jackson A, et al. Prescription drug abuse: an introduction. http://www.drugabuse.gov/sites/default/files/prescription-drug-abuse-alt.pdf. Published November 8, 2009. Accessed June 20, 2012.
18. Passik SD, Kirsh KL, Whitcomb L, et al. Monitoring outcomes during long-term opioid therapy for noncancer pain: results with the Pain Assessment and Documentation Tool. J Opioid Manag. 2005;1(5):257-266.
19. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005;6(6):432-442.
20. Passik SD. Pain management misstatements: ceiling effects red and yellow flags. Pain Med. 2006;7(1):76-77.
21. Diagnostic and statistical manual of mental disorders 4th ed text rev. Washington DC: American Psychiatric Association; 2000.
22. Mee-Lee D, Shulman GD, Fishman MJ, et al. eds. ASAM patient placement criteria for the treatment of substance-related disorders. 2nd ed. Chevy Chase, MD: American Society of Addiction Medicine, Inc.; 2001.
23. Banta-Green CJ, Maynard C, Koepsell TD, et al. Retention in methadone maintenance drug treatment for prescription-type opioid primary users compared to heroin users. Addiction. 2009;104(5):775-783.
24. Moore BA, Fiellin DA, Barry DT, et al. Primary care office-based buprenorphine treatment: comparison of heroin and prescription opioid dependent patients. J Gen Intern Med. 2007;22(4):527-530.
25. Weiss RD, Potter JS, Fiellin DA, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry. 2011;68(12):1238-1246.
26. U.S. Department of Health and Human Services (HHS). Substance Abuse and Mental Health Services Administration (SAMHSA). Office of Applied Studies. Treatment Episode Data Set (TEDS). 1998 - 2008. National Admissions to Substance Abuse Treatment Services, DASIS Series: S-50, HHS Publication No. (SMA) 09-4471. Rockville, MD; 2010.
27. Minozzi S, Amato L, Vecchi S, et al. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database Syst Rev. 2011;(4):CD001333.-
1. U.S. Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Office of Applied Studies. Results from the 2009 national survey on drug use and health: volume I. http://www.samhsa.gov/data/NSDUH/2k9NSDUH/2k9Results.htm. Accessed June 20, 2012.
2. Warner M, Chen LH, Makuc DM, et al. Drug poisoning deaths in the United States, 1980-2008. http://www.cdc.gov/nchs/data/databriefs/db81.htm. Published December 2011. Accessed June 20, 2012.
3. Centers for Disease Control and Prevention (CDC). Emergency department visits involving nonmedical use of selected prescription drugs - United States 2004-2008. MMWR Morb Mortal Wkly Rep. 2010;59(23):705-709.
4. Weaver M, Schnoll S. Addiction issues in prescribing opioids for chronic nonmalignant pain. J Addict Med. 2007;1(1):2-10.
5. American Psychiatric Association. R 19 opioid use disorder. http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460. Updated April 30 2012. Accessed June 20, 2012.
6. Savage SR, Horvath R. Opioid therapy of pain. In: Ries RK Fiellin DA, Miller SC, et al, eds. Principles of addiction medicine. 4th ed. Hagerstown, MD: Lippincott Williams & Wilkins; 2009:1329-1351.
7. Fishbain DA, Cole B, Lewis J, et al. What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? A structured evidence-based review. Pain Med. 2008;9(4):444-459.
8. Gourlay DL, Heit HA. Pain and addiction: managing risk through comprehensive care. J Addict Dis. 2008;27(3):23-30.
9. Boscarino JA, Rukstalis MR, Hoffman SN, et al. Prevalence of prescription opioid-use disorder among chronic pain patients: comparison of the DSM-5 vs. DSM-4 diagnostic criteria. J Addict Dis. 2011;30(3):185-194.
10. Starrels JL, Becker WC, Weiner MG, et al. Low use of opioid risk reduction strategies in primary care even for high risk patients with chronic pain. J Gen Intern Med. 2011;26(9):958-964.
11. Miller NS. Failure of enforcement controlled substance laws in health policy for prescribing opiate medications: a painful assessment of morbidity and mortality. Am J Ther. 2006;13(6):527-533.
12. Turk DC, Swanson KS, Gatchel RJ. Predicting opioid misuse by chronic pain patients: a systematic review and literature synthesis. Clin J Pain. 2008;24(6):497-508.
13. Miller NS, Greenfeld A. Patient characteristics and risks factors for development of dependence on hydrocodone and oxycodone. Am J Ther. 2004;11(1):26-32.
14. Butler SF, Budman SH, Fernandez KC, et al. Cross-validation of a Screener to Predict Opioid Misuse in Chronic Pain Patients (SOAPP-R). J Addict Med. 2009;3(2):66-73.
15. Passik SD, Kirsh KL, Casper D. Addiction-related assessment tools and pain management: instruments for screening treatment planning, and monitoring compliance. Pain Med. 2008;9(suppl 2):S145-S166.
16. Chou R, Fanciullo GJ, Fine PG, et al. Opioids for chronic noncancer pain: prediction and identification of aberrant drug-related behaviors: a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. J Pain. 2009;10(2):131-146.
17. Alford DP, Liebschutz J, Jackson A, et al. Prescription drug abuse: an introduction. http://www.drugabuse.gov/sites/default/files/prescription-drug-abuse-alt.pdf. Published November 8, 2009. Accessed June 20, 2012.
18. Passik SD, Kirsh KL, Whitcomb L, et al. Monitoring outcomes during long-term opioid therapy for noncancer pain: results with the Pain Assessment and Documentation Tool. J Opioid Manag. 2005;1(5):257-266.
19. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005;6(6):432-442.
20. Passik SD. Pain management misstatements: ceiling effects red and yellow flags. Pain Med. 2006;7(1):76-77.
21. Diagnostic and statistical manual of mental disorders 4th ed text rev. Washington DC: American Psychiatric Association; 2000.
22. Mee-Lee D, Shulman GD, Fishman MJ, et al. eds. ASAM patient placement criteria for the treatment of substance-related disorders. 2nd ed. Chevy Chase, MD: American Society of Addiction Medicine, Inc.; 2001.
23. Banta-Green CJ, Maynard C, Koepsell TD, et al. Retention in methadone maintenance drug treatment for prescription-type opioid primary users compared to heroin users. Addiction. 2009;104(5):775-783.
24. Moore BA, Fiellin DA, Barry DT, et al. Primary care office-based buprenorphine treatment: comparison of heroin and prescription opioid dependent patients. J Gen Intern Med. 2007;22(4):527-530.
25. Weiss RD, Potter JS, Fiellin DA, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry. 2011;68(12):1238-1246.
26. U.S. Department of Health and Human Services (HHS). Substance Abuse and Mental Health Services Administration (SAMHSA). Office of Applied Studies. Treatment Episode Data Set (TEDS). 1998 - 2008. National Admissions to Substance Abuse Treatment Services, DASIS Series: S-50, HHS Publication No. (SMA) 09-4471. Rockville, MD; 2010.
27. Minozzi S, Amato L, Vecchi S, et al. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database Syst Rev. 2011;(4):CD001333.-
Opioid use disorder during pregnancy
Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/opioid-use-disorder-during-pregnancy.html#comments
For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.
Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.
After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.
Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.1 This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.2
Early identification is crucial
Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use3 and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.4 Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.5
Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.6
Chasnoff et al7 studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:
- physical examination findings or history that suggests substance use or withdrawal symptoms
- positive drug test results for illicit or nonprescribed opioids
- aberrant medication-taking behaviors in those receiving prescribed opioids
- nicotine or alcohol use in the month before they knew they were pregnant
- a history of addiction-related disorders
- evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
- poor prenatal care attendance
- unexplained fetal growth abnormalities.
9 OUD-specific screening approaches are lacking; screening for general substance use is discussed elsewhere in the literature.10
A combination of interviewing and biologic drug screening may be more effective than either approach alone.11 Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.
Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.2
Table 1
The ‘4P’s Plus’ screen for substance use during pregnancy
| Parents: Did either of your parents ever have a problem with alcohol or drugs? |
| Partner: Does your partner have a problem with alcohol or drugs? |
| Past: Have you ever drunk beer, wine, or liquor? |
| Pregnancy: In the month before you knew you were pregnant, how many cigarettes did you smoke? |
| In the month before you knew you were pregnant, how many beers/how much wine/ how much liquor did you drink? |
| A positive screen results when a patient answers either of the 2 questions relating to pregnancy, indicating any alcohol or tobacco use in the month before she knew she was pregnant |
| Source: Reference 8 |
Office management
OUD-specific treatment decreases opioid use and improves birth outcomes14 ; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.5 The Addiction Severity Index version tailored to women and pregnancy15 examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.16 Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.5,17,18
Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.5
Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.12
Table 2
Medical complications common to pregnancy and substance abuse
| Anemia |
| Bacteremia/sepsis |
| Endocarditis |
| Cellulitis |
| Depression/anxiety |
| Gestational diabetes |
| Hepatitis (chronic and acute) |
| Hypertension/tachycardia |
| Phlebitis |
| Pneumonia |
| Gingivitis/poor oral hygiene |
| Sexually transmitted diseases |
|
| Tetanus |
| Cystitis |
| Pyelonephritis |
| AIDS: acquired immune deficiency syndrome; HIV: human immunodeficiency virus |
| Source: Reference 6 |
Table 3
Obstetric complications in women with addiction disorders
| Placental abruption |
| Chorioamnionitis |
| Placental insufficiency |
| Intrauterine growth restriction |
| Hypoxic/ischemic brain injury |
| Meconium passage |
| Neonatal abstinence syndrome |
| Spontaneous abortion |
| Intrauterine fetal death |
| Premature labor and delivery |
| Preterm, premature rupture of membranes |
| Postpartum hemorrhage |
| Hypertensive emergencies/preeclampsia |
| Source: Reference 6 |
Opioid agonist therapy
Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives ( Table 4 ).20
Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:
- their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
- their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
- research on the use of naltrexone during pregnancy is lacking.
Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.22-24
The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.28 However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.
Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.
In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.29
Table 4
Opioid agonist treatment objectives for addicted patients who are pregnant
| General objectives |
| Prevent opioid withdrawal signs and symptoms |
| Provide a comfortable induction onto the medication |
| Block the euphoric and reinforcing effects of illicit opioids while also attenuating the motivation (craving, social interactions) to use illicit opioids and other drugs |
| Enhance treatment retention |
| Create a more optimal environment for behavioral and psychosocial interventions |
| Pregnancy-specific objectives |
| Eliminate or reduce fetal exposure to illicit opioids and other illicit drugs |
| Stabilize the intrauterine environment |
| Enhance involvement in prenatal care |
| Create an optimal environment to address pregnancy-specific problems |
| Source: Reference 20 |
Delivery and postnatal care
Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.30
During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.31 Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.
To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.
CASE CONTINUED: Medication change
Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.
After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.
Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.
- Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
- Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
- Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
- Aripiprazole • Abilify
- Buprenorphine and naloxone •Suboxone
- Buprenorphine • Subutex
- Butorphanol • Stadol
- Citalopram • Celexa
- Fentanyl • Duragesic, Sublimaze, others
- Methadone • Dolophine
- Naloxone • Narcan
- Naltrexone • ReVia
- Nalbuphine • Nubain
- Oxycodone • Oxycontin
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.
Acknowledgments
The authors wish to thank Kathleen Peak for her administrative assistance and Paul Horn, Professor, Department of Mathematical Sciences and Cincinnati VA, for statistical assistance.
Methadone is compatible with breast-feedinga and the American Academy of Pediatricsb and World Health Organizationc recommend breast-feeding for women receiving methadone unless there are contraindications such as human immunodeficiency virus infection.a Instruct mothers to seek medical advice if their breast-fed infant appears sedated.b Because the amount of methadone in breast milk is very small and depends on the methadone dose, the breast milk of mothers receiving methadone may be insufficient to prevent neonatal abstinence syndrome (NAS) and infants still may require opioid agonist treatment.d
Although breast-feeding by mothers receiving buprenorphine is not recommended by the drug’s manufacturer, there is consensus that buprenorphine is found in low levels in breast milke, f and is compatible with breast-feeding.g Because of partial agonism and low oral bioavailability, buprenorphine may not suppress NAS from methadone withdrawal. Always obtain appropriate informed consent.
References
a. Chasnoff If, Neuman MA, Thornton C, et al. Screening for substance abuse in pregnancy: a practical approach for the primary care physician. Am J Obstet Gynecol. 2001;184(4):752-758.
b. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human breast milk. Pediatrics. 2001;108:776-789.
c. The WHO Working Group, Bennet PN, ed. Monographs on individual drugs (WHO Working Group). In: Drugs and human lactation. Amsterdam, The Netherlands: Elsevier; 1988:319-320.
d. Jansson LM, Velez M, Harrow C. Methadone maintenance and lactation: a review of the literature and current management guidelines. J Hum Lact. 2004;20(1):62-71.
e. Grimm D, Pauly E, Pöschl J, et al. Buprenorphine and norbuprenorphine concentrations in human breast milk samples determined by liquid chromotography-tandem mass spectrometry. Ther Drug Monit. 2005;27(4):526-530.
f. Lindemalm S, Nydert P, Svensson JO, et al. Transfer of buprenorphine into breast milk and calculation of infant drug dose. J Hum Lact. 2009;25(2):199-205.
g. Center for Substance Abuse Treatment. Special populations: pregnant women and neonates. In: Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP)) Series 40. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2004. DHHS Publication No. (SMA) 04-3939.
1. Flavin J, Paltrow LM. Punishing pregnant drug-using women: defying law medicine, and common sense. J Addict Dis. 2010;29(2):231-244.
2. American Psychiatric Association. Opioid use disorder. DSM-5 development. Available at: http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460#. Accessed January 26 2011.
3. Pichini S, Puig C, Zuccaro P, et al. Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: preliminary results of the “Meconium Project. “ Forensic Sci Int. 2005;153:59-65.
4. Mitchell JL, Brown G. Physiological effects of cocaine heroin, and methadone. In: Engs RC, ed. Women: alcohol and other drugs. Dubuque, IA: Kendall/Hunt Publishing Co; 1990:53-60.
5. Center for Substance Abuse Treatment. Medication-assisted treatment for opioid addiction during pregnancy. In: Medication-assisted treatment for opioid addiction in opioid treatment programs. Treatment Improvement Protocol (TIP) Series 43. Rockville MD: Substance Abuse and Mental Health Services Administration; 2005, reprinted 2006. DHHS Publication No. (SMA) 06-4212.
6. Helmbrecht GD, Thiagarajah S. Management of addiction disorders in pregnancy. J Addict Med. 2008;2(1):1-16.
7. Chasnoff If, Neuman MA, Thornton C, et al. Screening for substance abuse in pregnancy: a practical approach for the primary care physician. Am J Obstet Gynecol. 2001;184(4):752-758.
8. Chasnoff IJ, Wells AM, McGourty RF, et al. Validation of the 4P’s Plus screen for substance use in pregnancy validation of the 4P’s Plus. J Perinatol. 2007;27:744-748.
9. Jones HE. The challenges of screening for substance use in pregnant women: commentary on the 4P’s Plus tool. J Perinatol. 2005;25:365-367.
10. Center for Substance Abuse Treatment. Substance abuse treatment: addressing the specific needs of women. Treatment Improvement Protocol (TIP) Series 51. Rockville MD: Substance Abuse and Mental Health Services Administration; 2009. HHS Publication No. (SMA) 09-4426.
11. Christmas JT, Knisely JS, Dawson KS, et al. Comparison of questionnaire screening and urine toxicology for detection of pregnancy complicated by substance use. Obstet Gynecol. 1992;80:750-754.
12. Wunsch MJ, Weaver MF. Alcohol and other drug use during pregnancy: management of the mother and child. In: Ries RK Fiellin DA, Miller SC, et al, eds. Principles of addiction medicine, 4th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2009:1111-1124.
13. Ondersma SJ, Winhusen T, Erickson SJ, et al. Motivation enhancement therapy with pregnant substance-abusing women: does baseline motivation moderate efficacy? Drug Alcohol Depend. 2009;101(1-2):74-79.
14. Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy: effects and management. Obstet Gynecol Clin North Am. 1998;25:139-151.
15. Comfort M, Zanis DA, Whiteley MJ, et al. Assessing the needs of substance abusing women. Psychometric data on the psychosocial history. J Subst Abuse Treat. 1999;17:79-83.
16. Kissin WB, Svikis DS, Moylan P, et al. Identifying pregnant women at risk for early attrition from substance abuse treatment. J Subst Abuse Treat. 2004;27:31-38.
17. Jones HE, O’Grady KE, Malfi D, et al. Methadone maintenance vs. methadone taper during pregnancy: maternal and neonatal outcomes. Am J Addict. 2008;17(5):372-386.
18. Luty J, Nikolaou V, Bearn J. Is opiate detoxification unsafe in pregnancy? J Subst Abuse Treat. 2003;24(4):363-367.
19. Vesga-Lopez O, Blanco C, Keyes K, et al. Psychiatric disorders in pregnant and postpartum women in the United States. Arch Gen Psychiatry. 2008;65(7):805-815.
20. Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008;35(3):245-259.
21. NIDA International Program. National Institute on Drug Abuse. Methadone research web guide. Available at: http://international.drugabuse.gov/collaboration/guide_methadone/index.html. Accessed December 2, 2010.
22. Wittmann BK, Segal S. A comparison of the effects of single- and split-dose methadone administration on the fetus: ultrasound evaluation. Int J Addict. 1991;26:213-218.
23. DePetrillo PB, Rice JM. Methadone dosing and pregnancy: impact on program compliance. Int J Addict. 1995;30:207-217.
24. Jansson LM, Dipietro JA, Velez M, et al. Maternal methadone dosing schedule and fetal neurobehaviour. J Matern Fetal Neonatal Med. 2009;22(1):29-35.
25. Center for Substance Abuse Treatment. Special populations: pregnant women and neonates. In: Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP) Series 40. Rockville MD: Substance Abuse and Mental Health Services Administration; 2004. DHHS Publication No. (SMA) 04-3939.
26. Jones HE, Johnson RE, Jasinski DR, et al. Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone. Drug Alcohol Depend. 2005;78(1):33-38.
27. Jones HE, Johnson RE, Jasinski DR, et al. Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients; effects on the neonatal abstinence syndrome. Drug Alcohol Depend. 2005;79(1):1-10.
28. Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010;363(24):2320-2331.
29. Nanovskaya T, Deshmukh S, Brooks M, et al. Transplacental transfer and metabolism of buprenorphine. J Pharmacol Exp Ther. 2002;300(1):26-33.
30. Svikis DS, Golden AS, Huggins GR, et al. Cost-effectiveness of treatment for drug-abusing pregnant women. Drug Alcohol Depend. 1997;45:105-113.
31. Jones HE, O’Grady K, Dahne J, et al. Management of acute postpartum pain in patients maintained on methadone or buprenorphine during pregnancy. Am J Drug Alcohol Abuse. 2009;35(3):151-156.
Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/opioid-use-disorder-during-pregnancy.html#comments
For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.
Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.
After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.
Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.1 This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.2
Early identification is crucial
Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use3 and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.4 Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.5
Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.6
Chasnoff et al7 studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:
- physical examination findings or history that suggests substance use or withdrawal symptoms
- positive drug test results for illicit or nonprescribed opioids
- aberrant medication-taking behaviors in those receiving prescribed opioids
- nicotine or alcohol use in the month before they knew they were pregnant
- a history of addiction-related disorders
- evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
- poor prenatal care attendance
- unexplained fetal growth abnormalities.
9 OUD-specific screening approaches are lacking; screening for general substance use is discussed elsewhere in the literature.10
A combination of interviewing and biologic drug screening may be more effective than either approach alone.11 Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.
Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.2
Table 1
The ‘4P’s Plus’ screen for substance use during pregnancy
| Parents: Did either of your parents ever have a problem with alcohol or drugs? |
| Partner: Does your partner have a problem with alcohol or drugs? |
| Past: Have you ever drunk beer, wine, or liquor? |
| Pregnancy: In the month before you knew you were pregnant, how many cigarettes did you smoke? |
| In the month before you knew you were pregnant, how many beers/how much wine/ how much liquor did you drink? |
| A positive screen results when a patient answers either of the 2 questions relating to pregnancy, indicating any alcohol or tobacco use in the month before she knew she was pregnant |
| Source: Reference 8 |
Office management
OUD-specific treatment decreases opioid use and improves birth outcomes14 ; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.5 The Addiction Severity Index version tailored to women and pregnancy15 examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.16 Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.5,17,18
Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.5
Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.12
Table 2
Medical complications common to pregnancy and substance abuse
| Anemia |
| Bacteremia/sepsis |
| Endocarditis |
| Cellulitis |
| Depression/anxiety |
| Gestational diabetes |
| Hepatitis (chronic and acute) |
| Hypertension/tachycardia |
| Phlebitis |
| Pneumonia |
| Gingivitis/poor oral hygiene |
| Sexually transmitted diseases |
|
| Tetanus |
| Cystitis |
| Pyelonephritis |
| AIDS: acquired immune deficiency syndrome; HIV: human immunodeficiency virus |
| Source: Reference 6 |
Table 3
Obstetric complications in women with addiction disorders
| Placental abruption |
| Chorioamnionitis |
| Placental insufficiency |
| Intrauterine growth restriction |
| Hypoxic/ischemic brain injury |
| Meconium passage |
| Neonatal abstinence syndrome |
| Spontaneous abortion |
| Intrauterine fetal death |
| Premature labor and delivery |
| Preterm, premature rupture of membranes |
| Postpartum hemorrhage |
| Hypertensive emergencies/preeclampsia |
| Source: Reference 6 |
Opioid agonist therapy
Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives ( Table 4 ).20
Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:
- their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
- their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
- research on the use of naltrexone during pregnancy is lacking.
Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.22-24
The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.28 However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.
Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.
In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.29
Table 4
Opioid agonist treatment objectives for addicted patients who are pregnant
| General objectives |
| Prevent opioid withdrawal signs and symptoms |
| Provide a comfortable induction onto the medication |
| Block the euphoric and reinforcing effects of illicit opioids while also attenuating the motivation (craving, social interactions) to use illicit opioids and other drugs |
| Enhance treatment retention |
| Create a more optimal environment for behavioral and psychosocial interventions |
| Pregnancy-specific objectives |
| Eliminate or reduce fetal exposure to illicit opioids and other illicit drugs |
| Stabilize the intrauterine environment |
| Enhance involvement in prenatal care |
| Create an optimal environment to address pregnancy-specific problems |
| Source: Reference 20 |
Delivery and postnatal care
Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.30
During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.31 Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.
To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.
CASE CONTINUED: Medication change
Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.
After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.
Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.
- Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
- Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
- Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
- Aripiprazole • Abilify
- Buprenorphine and naloxone •Suboxone
- Buprenorphine • Subutex
- Butorphanol • Stadol
- Citalopram • Celexa
- Fentanyl • Duragesic, Sublimaze, others
- Methadone • Dolophine
- Naloxone • Narcan
- Naltrexone • ReVia
- Nalbuphine • Nubain
- Oxycodone • Oxycontin
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.
Acknowledgments
The authors wish to thank Kathleen Peak for her administrative assistance and Paul Horn, Professor, Department of Mathematical Sciences and Cincinnati VA, for statistical assistance.
Methadone is compatible with breast-feedinga and the American Academy of Pediatricsb and World Health Organizationc recommend breast-feeding for women receiving methadone unless there are contraindications such as human immunodeficiency virus infection.a Instruct mothers to seek medical advice if their breast-fed infant appears sedated.b Because the amount of methadone in breast milk is very small and depends on the methadone dose, the breast milk of mothers receiving methadone may be insufficient to prevent neonatal abstinence syndrome (NAS) and infants still may require opioid agonist treatment.d
Although breast-feeding by mothers receiving buprenorphine is not recommended by the drug’s manufacturer, there is consensus that buprenorphine is found in low levels in breast milke, f and is compatible with breast-feeding.g Because of partial agonism and low oral bioavailability, buprenorphine may not suppress NAS from methadone withdrawal. Always obtain appropriate informed consent.
References
a. Chasnoff If, Neuman MA, Thornton C, et al. Screening for substance abuse in pregnancy: a practical approach for the primary care physician. Am J Obstet Gynecol. 2001;184(4):752-758.
b. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human breast milk. Pediatrics. 2001;108:776-789.
c. The WHO Working Group, Bennet PN, ed. Monographs on individual drugs (WHO Working Group). In: Drugs and human lactation. Amsterdam, The Netherlands: Elsevier; 1988:319-320.
d. Jansson LM, Velez M, Harrow C. Methadone maintenance and lactation: a review of the literature and current management guidelines. J Hum Lact. 2004;20(1):62-71.
e. Grimm D, Pauly E, Pöschl J, et al. Buprenorphine and norbuprenorphine concentrations in human breast milk samples determined by liquid chromotography-tandem mass spectrometry. Ther Drug Monit. 2005;27(4):526-530.
f. Lindemalm S, Nydert P, Svensson JO, et al. Transfer of buprenorphine into breast milk and calculation of infant drug dose. J Hum Lact. 2009;25(2):199-205.
g. Center for Substance Abuse Treatment. Special populations: pregnant women and neonates. In: Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP)) Series 40. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2004. DHHS Publication No. (SMA) 04-3939.
Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/opioid-use-disorder-during-pregnancy.html#comments
For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.
Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.
After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.
Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.1 This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.2
Early identification is crucial
Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use3 and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.4 Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.5
Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.6
Chasnoff et al7 studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:
- physical examination findings or history that suggests substance use or withdrawal symptoms
- positive drug test results for illicit or nonprescribed opioids
- aberrant medication-taking behaviors in those receiving prescribed opioids
- nicotine or alcohol use in the month before they knew they were pregnant
- a history of addiction-related disorders
- evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
- poor prenatal care attendance
- unexplained fetal growth abnormalities.
9 OUD-specific screening approaches are lacking; screening for general substance use is discussed elsewhere in the literature.10
A combination of interviewing and biologic drug screening may be more effective than either approach alone.11 Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.
Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.2
Table 1
The ‘4P’s Plus’ screen for substance use during pregnancy
| Parents: Did either of your parents ever have a problem with alcohol or drugs? |
| Partner: Does your partner have a problem with alcohol or drugs? |
| Past: Have you ever drunk beer, wine, or liquor? |
| Pregnancy: In the month before you knew you were pregnant, how many cigarettes did you smoke? |
| In the month before you knew you were pregnant, how many beers/how much wine/ how much liquor did you drink? |
| A positive screen results when a patient answers either of the 2 questions relating to pregnancy, indicating any alcohol or tobacco use in the month before she knew she was pregnant |
| Source: Reference 8 |
Office management
OUD-specific treatment decreases opioid use and improves birth outcomes14 ; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.5 The Addiction Severity Index version tailored to women and pregnancy15 examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.16 Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.5,17,18
Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.5
Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.12
Table 2
Medical complications common to pregnancy and substance abuse
| Anemia |
| Bacteremia/sepsis |
| Endocarditis |
| Cellulitis |
| Depression/anxiety |
| Gestational diabetes |
| Hepatitis (chronic and acute) |
| Hypertension/tachycardia |
| Phlebitis |
| Pneumonia |
| Gingivitis/poor oral hygiene |
| Sexually transmitted diseases |
|
| Tetanus |
| Cystitis |
| Pyelonephritis |
| AIDS: acquired immune deficiency syndrome; HIV: human immunodeficiency virus |
| Source: Reference 6 |
Table 3
Obstetric complications in women with addiction disorders
| Placental abruption |
| Chorioamnionitis |
| Placental insufficiency |
| Intrauterine growth restriction |
| Hypoxic/ischemic brain injury |
| Meconium passage |
| Neonatal abstinence syndrome |
| Spontaneous abortion |
| Intrauterine fetal death |
| Premature labor and delivery |
| Preterm, premature rupture of membranes |
| Postpartum hemorrhage |
| Hypertensive emergencies/preeclampsia |
| Source: Reference 6 |
Opioid agonist therapy
Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives ( Table 4 ).20
Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:
- their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
- their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
- research on the use of naltrexone during pregnancy is lacking.
Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.22-24
The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.28 However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.
Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.
In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.29
Table 4
Opioid agonist treatment objectives for addicted patients who are pregnant
| General objectives |
| Prevent opioid withdrawal signs and symptoms |
| Provide a comfortable induction onto the medication |
| Block the euphoric and reinforcing effects of illicit opioids while also attenuating the motivation (craving, social interactions) to use illicit opioids and other drugs |
| Enhance treatment retention |
| Create a more optimal environment for behavioral and psychosocial interventions |
| Pregnancy-specific objectives |
| Eliminate or reduce fetal exposure to illicit opioids and other illicit drugs |
| Stabilize the intrauterine environment |
| Enhance involvement in prenatal care |
| Create an optimal environment to address pregnancy-specific problems |
| Source: Reference 20 |
Delivery and postnatal care
Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.30
During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.31 Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.
To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.
CASE CONTINUED: Medication change
Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.
After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.
Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.
- Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
- Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
- Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
- Aripiprazole • Abilify
- Buprenorphine and naloxone •Suboxone
- Buprenorphine • Subutex
- Butorphanol • Stadol
- Citalopram • Celexa
- Fentanyl • Duragesic, Sublimaze, others
- Methadone • Dolophine
- Naloxone • Narcan
- Naltrexone • ReVia
- Nalbuphine • Nubain
- Oxycodone • Oxycontin
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.
Acknowledgments
The authors wish to thank Kathleen Peak for her administrative assistance and Paul Horn, Professor, Department of Mathematical Sciences and Cincinnati VA, for statistical assistance.
Methadone is compatible with breast-feedinga and the American Academy of Pediatricsb and World Health Organizationc recommend breast-feeding for women receiving methadone unless there are contraindications such as human immunodeficiency virus infection.a Instruct mothers to seek medical advice if their breast-fed infant appears sedated.b Because the amount of methadone in breast milk is very small and depends on the methadone dose, the breast milk of mothers receiving methadone may be insufficient to prevent neonatal abstinence syndrome (NAS) and infants still may require opioid agonist treatment.d
Although breast-feeding by mothers receiving buprenorphine is not recommended by the drug’s manufacturer, there is consensus that buprenorphine is found in low levels in breast milke, f and is compatible with breast-feeding.g Because of partial agonism and low oral bioavailability, buprenorphine may not suppress NAS from methadone withdrawal. Always obtain appropriate informed consent.
References
a. Chasnoff If, Neuman MA, Thornton C, et al. Screening for substance abuse in pregnancy: a practical approach for the primary care physician. Am J Obstet Gynecol. 2001;184(4):752-758.
b. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human breast milk. Pediatrics. 2001;108:776-789.
c. The WHO Working Group, Bennet PN, ed. Monographs on individual drugs (WHO Working Group). In: Drugs and human lactation. Amsterdam, The Netherlands: Elsevier; 1988:319-320.
d. Jansson LM, Velez M, Harrow C. Methadone maintenance and lactation: a review of the literature and current management guidelines. J Hum Lact. 2004;20(1):62-71.
e. Grimm D, Pauly E, Pöschl J, et al. Buprenorphine and norbuprenorphine concentrations in human breast milk samples determined by liquid chromotography-tandem mass spectrometry. Ther Drug Monit. 2005;27(4):526-530.
f. Lindemalm S, Nydert P, Svensson JO, et al. Transfer of buprenorphine into breast milk and calculation of infant drug dose. J Hum Lact. 2009;25(2):199-205.
g. Center for Substance Abuse Treatment. Special populations: pregnant women and neonates. In: Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP)) Series 40. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2004. DHHS Publication No. (SMA) 04-3939.
1. Flavin J, Paltrow LM. Punishing pregnant drug-using women: defying law medicine, and common sense. J Addict Dis. 2010;29(2):231-244.
2. American Psychiatric Association. Opioid use disorder. DSM-5 development. Available at: http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460#. Accessed January 26 2011.
3. Pichini S, Puig C, Zuccaro P, et al. Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: preliminary results of the “Meconium Project. “ Forensic Sci Int. 2005;153:59-65.
4. Mitchell JL, Brown G. Physiological effects of cocaine heroin, and methadone. In: Engs RC, ed. Women: alcohol and other drugs. Dubuque, IA: Kendall/Hunt Publishing Co; 1990:53-60.
5. Center for Substance Abuse Treatment. Medication-assisted treatment for opioid addiction during pregnancy. In: Medication-assisted treatment for opioid addiction in opioid treatment programs. Treatment Improvement Protocol (TIP) Series 43. Rockville MD: Substance Abuse and Mental Health Services Administration; 2005, reprinted 2006. DHHS Publication No. (SMA) 06-4212.
6. Helmbrecht GD, Thiagarajah S. Management of addiction disorders in pregnancy. J Addict Med. 2008;2(1):1-16.
7. Chasnoff If, Neuman MA, Thornton C, et al. Screening for substance abuse in pregnancy: a practical approach for the primary care physician. Am J Obstet Gynecol. 2001;184(4):752-758.
8. Chasnoff IJ, Wells AM, McGourty RF, et al. Validation of the 4P’s Plus screen for substance use in pregnancy validation of the 4P’s Plus. J Perinatol. 2007;27:744-748.
9. Jones HE. The challenges of screening for substance use in pregnant women: commentary on the 4P’s Plus tool. J Perinatol. 2005;25:365-367.
10. Center for Substance Abuse Treatment. Substance abuse treatment: addressing the specific needs of women. Treatment Improvement Protocol (TIP) Series 51. Rockville MD: Substance Abuse and Mental Health Services Administration; 2009. HHS Publication No. (SMA) 09-4426.
11. Christmas JT, Knisely JS, Dawson KS, et al. Comparison of questionnaire screening and urine toxicology for detection of pregnancy complicated by substance use. Obstet Gynecol. 1992;80:750-754.
12. Wunsch MJ, Weaver MF. Alcohol and other drug use during pregnancy: management of the mother and child. In: Ries RK Fiellin DA, Miller SC, et al, eds. Principles of addiction medicine, 4th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2009:1111-1124.
13. Ondersma SJ, Winhusen T, Erickson SJ, et al. Motivation enhancement therapy with pregnant substance-abusing women: does baseline motivation moderate efficacy? Drug Alcohol Depend. 2009;101(1-2):74-79.
14. Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy: effects and management. Obstet Gynecol Clin North Am. 1998;25:139-151.
15. Comfort M, Zanis DA, Whiteley MJ, et al. Assessing the needs of substance abusing women. Psychometric data on the psychosocial history. J Subst Abuse Treat. 1999;17:79-83.
16. Kissin WB, Svikis DS, Moylan P, et al. Identifying pregnant women at risk for early attrition from substance abuse treatment. J Subst Abuse Treat. 2004;27:31-38.
17. Jones HE, O’Grady KE, Malfi D, et al. Methadone maintenance vs. methadone taper during pregnancy: maternal and neonatal outcomes. Am J Addict. 2008;17(5):372-386.
18. Luty J, Nikolaou V, Bearn J. Is opiate detoxification unsafe in pregnancy? J Subst Abuse Treat. 2003;24(4):363-367.
19. Vesga-Lopez O, Blanco C, Keyes K, et al. Psychiatric disorders in pregnant and postpartum women in the United States. Arch Gen Psychiatry. 2008;65(7):805-815.
20. Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008;35(3):245-259.
21. NIDA International Program. National Institute on Drug Abuse. Methadone research web guide. Available at: http://international.drugabuse.gov/collaboration/guide_methadone/index.html. Accessed December 2, 2010.
22. Wittmann BK, Segal S. A comparison of the effects of single- and split-dose methadone administration on the fetus: ultrasound evaluation. Int J Addict. 1991;26:213-218.
23. DePetrillo PB, Rice JM. Methadone dosing and pregnancy: impact on program compliance. Int J Addict. 1995;30:207-217.
24. Jansson LM, Dipietro JA, Velez M, et al. Maternal methadone dosing schedule and fetal neurobehaviour. J Matern Fetal Neonatal Med. 2009;22(1):29-35.
25. Center for Substance Abuse Treatment. Special populations: pregnant women and neonates. In: Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP) Series 40. Rockville MD: Substance Abuse and Mental Health Services Administration; 2004. DHHS Publication No. (SMA) 04-3939.
26. Jones HE, Johnson RE, Jasinski DR, et al. Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone. Drug Alcohol Depend. 2005;78(1):33-38.
27. Jones HE, Johnson RE, Jasinski DR, et al. Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients; effects on the neonatal abstinence syndrome. Drug Alcohol Depend. 2005;79(1):1-10.
28. Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010;363(24):2320-2331.
29. Nanovskaya T, Deshmukh S, Brooks M, et al. Transplacental transfer and metabolism of buprenorphine. J Pharmacol Exp Ther. 2002;300(1):26-33.
30. Svikis DS, Golden AS, Huggins GR, et al. Cost-effectiveness of treatment for drug-abusing pregnant women. Drug Alcohol Depend. 1997;45:105-113.
31. Jones HE, O’Grady K, Dahne J, et al. Management of acute postpartum pain in patients maintained on methadone or buprenorphine during pregnancy. Am J Drug Alcohol Abuse. 2009;35(3):151-156.
1. Flavin J, Paltrow LM. Punishing pregnant drug-using women: defying law medicine, and common sense. J Addict Dis. 2010;29(2):231-244.
2. American Psychiatric Association. Opioid use disorder. DSM-5 development. Available at: http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460#. Accessed January 26 2011.
3. Pichini S, Puig C, Zuccaro P, et al. Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: preliminary results of the “Meconium Project. “ Forensic Sci Int. 2005;153:59-65.
4. Mitchell JL, Brown G. Physiological effects of cocaine heroin, and methadone. In: Engs RC, ed. Women: alcohol and other drugs. Dubuque, IA: Kendall/Hunt Publishing Co; 1990:53-60.
5. Center for Substance Abuse Treatment. Medication-assisted treatment for opioid addiction during pregnancy. In: Medication-assisted treatment for opioid addiction in opioid treatment programs. Treatment Improvement Protocol (TIP) Series 43. Rockville MD: Substance Abuse and Mental Health Services Administration; 2005, reprinted 2006. DHHS Publication No. (SMA) 06-4212.
6. Helmbrecht GD, Thiagarajah S. Management of addiction disorders in pregnancy. J Addict Med. 2008;2(1):1-16.
7. Chasnoff If, Neuman MA, Thornton C, et al. Screening for substance abuse in pregnancy: a practical approach for the primary care physician. Am J Obstet Gynecol. 2001;184(4):752-758.
8. Chasnoff IJ, Wells AM, McGourty RF, et al. Validation of the 4P’s Plus screen for substance use in pregnancy validation of the 4P’s Plus. J Perinatol. 2007;27:744-748.
9. Jones HE. The challenges of screening for substance use in pregnant women: commentary on the 4P’s Plus tool. J Perinatol. 2005;25:365-367.
10. Center for Substance Abuse Treatment. Substance abuse treatment: addressing the specific needs of women. Treatment Improvement Protocol (TIP) Series 51. Rockville MD: Substance Abuse and Mental Health Services Administration; 2009. HHS Publication No. (SMA) 09-4426.
11. Christmas JT, Knisely JS, Dawson KS, et al. Comparison of questionnaire screening and urine toxicology for detection of pregnancy complicated by substance use. Obstet Gynecol. 1992;80:750-754.
12. Wunsch MJ, Weaver MF. Alcohol and other drug use during pregnancy: management of the mother and child. In: Ries RK Fiellin DA, Miller SC, et al, eds. Principles of addiction medicine, 4th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2009:1111-1124.
13. Ondersma SJ, Winhusen T, Erickson SJ, et al. Motivation enhancement therapy with pregnant substance-abusing women: does baseline motivation moderate efficacy? Drug Alcohol Depend. 2009;101(1-2):74-79.
14. Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy: effects and management. Obstet Gynecol Clin North Am. 1998;25:139-151.
15. Comfort M, Zanis DA, Whiteley MJ, et al. Assessing the needs of substance abusing women. Psychometric data on the psychosocial history. J Subst Abuse Treat. 1999;17:79-83.
16. Kissin WB, Svikis DS, Moylan P, et al. Identifying pregnant women at risk for early attrition from substance abuse treatment. J Subst Abuse Treat. 2004;27:31-38.
17. Jones HE, O’Grady KE, Malfi D, et al. Methadone maintenance vs. methadone taper during pregnancy: maternal and neonatal outcomes. Am J Addict. 2008;17(5):372-386.
18. Luty J, Nikolaou V, Bearn J. Is opiate detoxification unsafe in pregnancy? J Subst Abuse Treat. 2003;24(4):363-367.
19. Vesga-Lopez O, Blanco C, Keyes K, et al. Psychiatric disorders in pregnant and postpartum women in the United States. Arch Gen Psychiatry. 2008;65(7):805-815.
20. Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008;35(3):245-259.
21. NIDA International Program. National Institute on Drug Abuse. Methadone research web guide. Available at: http://international.drugabuse.gov/collaboration/guide_methadone/index.html. Accessed December 2, 2010.
22. Wittmann BK, Segal S. A comparison of the effects of single- and split-dose methadone administration on the fetus: ultrasound evaluation. Int J Addict. 1991;26:213-218.
23. DePetrillo PB, Rice JM. Methadone dosing and pregnancy: impact on program compliance. Int J Addict. 1995;30:207-217.
24. Jansson LM, Dipietro JA, Velez M, et al. Maternal methadone dosing schedule and fetal neurobehaviour. J Matern Fetal Neonatal Med. 2009;22(1):29-35.
25. Center for Substance Abuse Treatment. Special populations: pregnant women and neonates. In: Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP) Series 40. Rockville MD: Substance Abuse and Mental Health Services Administration; 2004. DHHS Publication No. (SMA) 04-3939.
26. Jones HE, Johnson RE, Jasinski DR, et al. Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone. Drug Alcohol Depend. 2005;78(1):33-38.
27. Jones HE, Johnson RE, Jasinski DR, et al. Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients; effects on the neonatal abstinence syndrome. Drug Alcohol Depend. 2005;79(1):1-10.
28. Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010;363(24):2320-2331.
29. Nanovskaya T, Deshmukh S, Brooks M, et al. Transplacental transfer and metabolism of buprenorphine. J Pharmacol Exp Ther. 2002;300(1):26-33.
30. Svikis DS, Golden AS, Huggins GR, et al. Cost-effectiveness of treatment for drug-abusing pregnant women. Drug Alcohol Depend. 1997;45:105-113.
31. Jones HE, O’Grady K, Dahne J, et al. Management of acute postpartum pain in patients maintained on methadone or buprenorphine during pregnancy. Am J Drug Alcohol Abuse. 2009;35(3):151-156.