Tapering opioids in patients with persistent pain after cancer treatment

Dear Editor, The number of patients surviving cancer for more than 5 years in the United States is projected to increase by 30% in the next decade to more than 16 million.1 After cancer treatment, approximately 10% of patients have persistent pain that is often treated with long-term opioids, which can lead to adverse effects, reduced quality of life, and misuse.2,3 Although the National Comprehensive Cancer Network guidelines recommend tapering long-term opioids, this recommendation may be difficult to interpret as it was based on evidence in non-cancer pain, rather than evidence from patients during or after cancer treatment.4 Not only is there limited guidance for tapering opioids in patients after cancer treatment but few studies explore the feasibility in this patient population. Thus, our objective was to implement and evaluate opioid tapering in a cancer center for patients who had persistent pain after cancer treatment. In this prospective cohort study, we implemented patient-centered tapering for adult patients who were prescribed long-term opioids and enrolled in the pain clinic at Vanderbilt-Ingram Cancer Center. The study period was from July 2021 to February 2023. We included patients regardless of treatment or lack of treatment received, with the last measures carried forward and data collected as part of routine care. We excluded patients if they were in end-of-life care during the first visit of the study period, did not complete at least one follow-up visit, or were tapering for violation of the opioid agreement. Participation was voluntary and the Institutional Review Board approved this study as quality improvement. We offered to partner with patients and slowly reduce the dose of opioids over 1 year. Patients who agreed to taper their opioids met with the care team, consisting of a chronic pain specialist (physician or nurse practitioner) and clinical pharmacist, to develop an individualized tapering protocol and were considered enrolled once the initial protocol was developed. The morphine equivalent daily dose (MEDD) was reduced by up to 5% in the first month and 10% in subsequent visits.5 The care team met with patients monthly to further taper opioids and modify adjuvant pain medications according to self-reported pain, functionality, and side effects. During monthly visits, the care team engaged in shared decision-making that was guided by the model proposed by Elwyn and colleagues.5–7 Primarily, the care team relied on patients to guide when to initiate and pause the taper protocol. Patients were asked to discuss tradeoffs between potential side-effects of additional treatment with functional limitations from pain. Harm reduction strategies were used throughout the taper and included weekly non-judgmental and non-coercive follow-up calls in the first month and as needed afterward, prescriptions for naloxone, and risk assessments with the Current Opioid Misuse Measure.8 Prescription opioid and substance use was assessed with bimonthly urine toxicology, and the care team assessed the Prescription Drug Monitoring Program before for issuing each opioid prescription. We offered addiction psychiatry referrals to patients at risk for harm. Patients were asked to complete the FACT-G (Functional Assessment of Cancer Therapy-General) and PEG-3 (Pain, Enjoyment of Life, and General Activity Scale) on initiating the opioid taper and then quarterly. We followed each patient for up to one year to assess the change in MEDD, FACT-G (0–108), PEG-3 (0–10), and adjuvant pain medications. Higher scores with the FACT-G indicate more interference with physical, social, emotional, and functional well-being, and higher scores with the PEG-3 indicate more pain intensity and interference with enjoyment of life and activity. Use of adjuvant pain medications (eg, pregabalin) was assessed at each visit. We assessed the change in outcomes using the Wilcoxon signed-rank test or paired t-test as appropriate. Among 321 patients, 110 patients were eligible and agreed to participate. Most were White (86.4%) and female (54.5%), and the mean (SD) age was 57 (11) years (Table 1). Nearly half of patients (47%) experienced recurrent cancer treatment during follow up, and 70% of patients were followed for one year. Most patients (89%) reduced their MEDD from baseline, and 6 (5.5%) patients stopped all opioids. The median (IQR) MEDD decreased from 308 (139–713) at baseline to 165 (60–494) (P < .001), which is equivalent to reducing oxycodone by 95 milligrams per day. The FACT-G remained the same (P = .71) and the mean (SD) PEG-3 slightly improved from 5.3 (2.2) at baseline to 4.8 (2.2) (P = .007). The mean (SD) adjuvant pain medications increased from 1.8 (1.2) at baseline to 2.4 (1.4) (P < 0.001), and 23 (21%) patients were initiated on buprenorphine. Figure 1 shows the MME change by the change in FACT-G, PEG-3, and adjuvant pain medications from baseline to follow up. Change from baseline to follow up in opioid dose (morphine equivalent daily dose) by change in (A) function, (B) pain, and (C) adjuvant pain medications. Negative scores in the figure for FACT-G and PEG-3 indicate improvement. Cohort characteristics and outcomes (n = 110). Patients could have one or more initial treatments. Abbreviations: IQR = interquartile range; SD = standard deviation. Cohort characteristics and outcomes (n = 110). Patients could have one or more initial treatments. Abbreviations: IQR = interquartile range; SD = standard deviation. This study provides needed evidence that the dose of opioids can be reduced in patients who have persistent pain after cancer treatment, without increasing pain or reducing function. We found tailoring adjuvant pain medications was crucial to voluntary continuation of opioid tapering.9 Buprenorphine was primarily used when full opioid agonist treatment was unsuccessful during the study. Since then, however, we have implemented buprenorphine as a first-line analgesic. In the absence of studies exploring opioid tapering in patients after cancer treatment, our finding that tapering opioids may not increase pain is similar to what others have found in patients with chronic pain. Frank and colleagues found that, among 10 studies implementing mandatory discontinuation of opioids in patients with chronic pain, 87% of patients were successful.10 Although our program was voluntary and did not require discontinuation, we found 89% of patients were able to reduce their dose of opioids. High-quality randomized trials evaluating the effectiveness of opioid tapering programs in chronic non-cancer and post-cancer pain are still needed. Findings from this study are limited to a single institution, relatively small sample size, and pragmatic study design. However, this study provides important information on useful strategies for and the feasibility of implementing a patient-centered, voluntary opioid tapering program for patients with persistent pain after cancer treatment. Future studies should explore tapering opioids in this patient population with randomized trials. T.J.R. was funded by the Agency for Healthcare Research and Quality grant number K08HS029695. Conflicts of interest: The authors have no conflicts of interest to disclose.