Overdose and Mental Health Crisis Common Long After Initiation of Opioid Tapering, Study Finds

Opioids include prescription pain medications (such as codeine [generic only], hydrocodone [HYSINGLA ER], morphine [MS CONTIN], oxycodone [OXAYDO, OXYCONTIN, ROXICODONE, ROXYBOND, XTAMPZA ER]), synthetic narcotics (such as fentanyl [ACTIQ, FENTORA]) and the illegal drug heroin.[1]

Because of the serious risks of prescription opioid pain medications — including abuse disorder, addiction, overdose and death — nonpharmacologic and non-opioid pharmacologic therapies should be used as first-line treatments for subacute or chronic pain, according to the new 2022 guideline for prescribing opioids for pain from the Centers for Disease Control and Prevention (CDC).[2]

Americans have been impacted by serious harms of these drugs at staggering rates. For example, opioids were involved in 75% of the nearly 92,000 U.S. drug-overdose deaths that occurred in 2020.[3]

Therefore, in addition to optimizing nondrug and non-opioid medications for patients with chronic pain, the 2022 CDC guideline recommended gradual dosage reductions of prescription opioids (tapering) or tapering and discontinuing these drugs among opioid users unless the benefits of their continued use outweigh their risks.[4]

There have been numerous reports of psychological distress, suicide and uncontrolled pain as well as serious withdrawal adverse events (see the Table below for a list of related symptoms) in patients who were physically dependent on opioid pain medications and had these medications discontinued suddenly or their dosage decreased rapidly.[5] This led the Food and Drug Administration to warn prescribers in 2019 against rapid discontinuation of prescription opioid pain medications, especially in long-term users of these medications.[6] The Department of Health and Human Services also issued a guide about appropriate dosage reduction or discontinuation of longterm opioid pain medications.[7]

Despite these guidelines, a new, large U.S. study provides a cautionary account of the aftermath of opioid-medication tapering in the real world, showing increased rates of overdose and mental health crises that persist during the second year after initiation of opioid tapering among patients taking stable, long-term, high-dose prescriptions of these medications. The study was conducted by researchers in the University of California, Davis, and published in the June 2022 issue of the Journal of the American Medical Association (JAMA) Network Open.

Table: Opioid Withdrawal Symptoms[8]

The new JAMA Network Open study[9]

Using a large U.S. administrative medical and pharmacy claims database pertaining to commercial insurance and Medicare Advantage enrollees, the researchers identified a cohort of 19,377 noncancer adult users of opioid medications. These patients were prescribed stable, high daily doses of prescription opioids (defined as 50 milligrams [mg] or higher of morphine or its equivalents) for at least 12 months (baseline year) before undergoing tapering of these medications within a subsequent seven-month period from 2008 to 2017. These patients did not have any records during the baseline year indicating use of buprenorphine (BUTRANS, SUBLOCADE), which is used to treat opioid dependence, or receipt of end-of-life, hospice or prolonged nursing-home care.

The researchers defined opioid tapering as at least 15% reduction in the mean daily dose of opioid medications from the baseline dose. They then identified emergency department visits or hospital admissions for two types of adverse events of interest: drug overdose, alcohol intoxication or drug withdrawal (hereafter overdose or withdrawal); and anxiety, depression, suicide attempt or intentional self-harm (hereafter mental health crisis).

Because their previous study found an increased risk of overdose and mental health crisis in the first year after tapering of long-term, stable-dose opioids,[10] the researchers hypothesized that there would be lower risks of these adverse events during a longer follow-up period after opioid tapering.

Therefore, for each patient in the new study, the researchers compared the rate of adverse events from 12 to 24 months after opioid tapering was initiated with the baseline rates of these outcomes. This method meant that each patient served as their “own control” in the comparison of adverse events before and after opioid tapering, which along with statistical adjustments for different characteristics between subjects helped in reducing bias in the study.

Contrary to the hypothesis, however, the rate of emergency department visits or hospital admissions for overdose or withdrawal increased by 57% in the 12 to 24 months after opioid tapering was initiated, compared with the before-tapering rate.

Similarly, the rate of emergency department visits or hospital admissions for mental health crisis was increased by 52% in the 12 to 24 months after opioid tapering was initiated, compared with the before-tapering rate.

The rates of emergency-department visits or hospital admissions for the study outcomes were highest for patients whose daily baseline opioid dose was more than 300 mg morphine equivalents.

The researchers concluded that their findings support careful monitoring and psychological support for at least two years after opioid tapering among long-term users of these medications, especially those taking higher doses.

What You Can Do

To manage pain, rely on non-drug therapy and non-opioid drugs whenever possible. If you have to take an opioid prescription for acute pain, talk to your doctor about taking the lowest effective dose of an immediate-release opioid. Note that using these medications for three days or less is usually adequate and using them for more than seven days is rarely needed.

Do not take opioid medications for chronic pain — outside of active cancer treatment, palliative care or end-of-life care — unless the benefits of these medications exceed their risks and you are under frequent care of a knowledgeable health care professional who has a plan for dose escalation and tapering of these medications.[11]

If you are a current long-term user of an opioid, do not stop it abruptly without first discussing with your health care professional how to slowly decrease your dosage and continue to manage your pain during this process.[12] Even when your opioid medication is decreased gradually, you still may experience withdrawal symptoms (see the Table above). Contact your health care professional immediately if you experience changes in your mood or thoughts of suicide, withdrawal symptoms or worsened pain.
 

References

[1] National Institute on Drug Abuse. Opioids. https://www.drugabuse.gov/drug-topics/opioids. Accessed November 3, 2022.

[2] Dowell D, Ragan KR, Jones CM, et al. CDC clinical practice guideline for prescribing opioids for pain — United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95.

[3] Centers for Disease Control and Prevention. Drug overdose. Death rate maps and graphs. June 2, 2022. https://www.cdc.gov/drugoverdose/deaths/index.html. Accessed November 3, 2022.

[4] Dowell D, Ragan KR, Jones CM, et al. CDC clinical practice guideline for prescribing opioids for pain — United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95.URL

[5] Food and Drug Administration. FDA identifies harm reported from sudden discontinuation of opioid pain medicines and requires label changes to guide prescribers on gradual, individualized tapering. April 9, 2019. https://www.fda.gov/media/122935/download. Accessed November 3, 2022.

[6] Ibid.

[7] Department of Health and Human Services. HHS guide for clinicians on the appropriate dosage reduction or discontinuation of long-term opioid analgesics. October 2019. https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf. Accessed November 3, 2022.

[8] Food and Drug Administration. FDA identifies harm reported from sudden discontinuation of opioid pain medicines and requires label changes to guide prescribers on gradual, individualized tapering. April 9, 2019. https://www.fda.gov/media/122935/download. Accessed November 3, 2022.

[9] Fenton JJ, Magnan E, Tseregounis IE, et al. Long-term risk of overdose or mental health crisis after opioid dose tapering. JAMA Netw Open. 2022;5(6):E2216726.

[10] Agnoli A, Xing G, Tancredi DJ, et al. Association of dose tapering with overdose or mental health crisis among patients prescribed long-term opioids. JAMA. 2021;326(5):411-419.

[11] Ibid.

[12] Food and Drug Administration. FDA identifies harm reported from sudden discontinuation of opioid pain medicines and requires label changes to guide prescribers on gradual, individualized tapering. April 9, 2019. https://www.fda.gov/media/122935/download. Accessed November 4, 2022.