Long-term opioid therapy trajectories and overdose in patients with and without cancer

Abstract

Objective: Pain is experienced by most patients with cancer and opioids are a cornerstone of management. Our objectives were (1) to identify patterns or trajectories of long-term opioid therapy (LTOT) and their correlates among patients with and without cancer and (2) to assess the association between trajectories and risk for opioid overdose, considering the potential moderating role of cancer.

Methods and analysis: We conducted a retrospective cohort study among individuals in the US Veterans Health Administration (VHA) database with incident LTOT with and without cancer (N=44,351; N=285,772, respectively) between 2010-2017. We investigated the relationship between LTOT trajectory and all International Classification of Diseases-9 and 10-defined accidental and intentional opioid-related overdoses.

Results: Trajectories of opioid receipt observed in patients without cancer and replicated in patients with cancer were: low-dose/stable trend, low-dose/de-escalating trend, moderate-dose/stable trend, moderate-dose/escalating with quadratic downturn trend, and high-dose/escalating with quadratic downturn trend. Time to first overdose was significantly predicted by higher-dose and escalating trajectories; the two low-dose trajectories conferred similar, lower risk. Conditional hazard ratios (99% CI) for the moderate-dose, moderate-dose/escalating with quadratic downturn and high-dose/escalating with quadratic downturn trends were 1·84 (1·18, 2·85), 2·56 (1·54, 4·25), and 2·41 (1·37, 4·26), respectively. Effects of trajectories on time to overdose did not differ by presence of cancer; inferences were replicated when restricting to patients with stage 3/4 cancer.

Conclusion: Patients with cancer face opioid overdose risks like patients without cancer. Future studies should seek to expand and address our knowledge about opioid risk in cancer patients.

Trial registration: None.

Figure 1

(A) Opioid dosing trajectories with percent-of-sample membership by cancer group. Note: Trajectory intercepts represent mg morphine equivalent daily dose (MEDD) start values and slope estimates represent mean linear and quadratic change in mg MEDD per 90-day interval. Intercepts (SE) and slopes (SE) for each trajectory for patients with and without cancer, respectively: low-dose/stable trend (intercept=16.74 (0.10); 15.97 (0.03)); (2) moderate-dose/stable trend (intercept=39.81 (0.14); 37.33 (0.03)); (3) low-dose/de-escalating trend (intercept=27.05 (0.16); 24.44 (0.05), linear slope= −5.00 (0.03); −4.45 (0.01)); (4) moderate-dose/escalating with quadratic downturn trend (intercept=58.29 (0.32); 58.50 (0.11), linear slope=5.05 (0.11); 3.81 (0.03), quadratic slope =−0.29 (0.01); −0.26 (0.00)); high dose/escalating with quadratic downturn trend (intercept=96.09 (0.40); 92.47 (0.16), linear slope=10.26 (0.19); 6.86 (0.05), quadratic slope =−0.64 (0.01); −0.41 (0.00)). (B) Median, IQR of opioid dose by time and latent trajectory.

Figure 2

Baseline cumulative incidence functions for opioid overdose by opioid dosing trajectory. Note: High-dose/escalating with quadratic downturn and moderate-dose/escalating with quadratic downturn trend trajectories have the steepest unconditional incidence functions for opioid overdose.