In patients with moderate to severe chronic back or osteoarthritic hip/knee pain, despite analgesic use, does opioid compared to non-opioid medication therapy result in better pain-related function?
In patients with severe back or hip/knee pain not currently receiving opioid therapy, there was no difference between opioid vs. non-opioid therapy used in an escalating treat-to-target approach over 12 months but there may be more adverse events associated with opioid therapy.
Long term opioid therapy had been the main stay of chronic pain for many years. These strong medications have significant side effects, including the risk of dependence. With the rising rates of serious side effects and opioid related deaths this pragmatic trial compared opioid to non-opioid therapy for benefit pain and quality of life measures and tracked adverse outcomes. Including 240 patients randomized to receive escalating doses in a treat-to-target strategy, over 12 months there was no difference in pain-related function for opioid vs. non-opioid, 3.4 vs 3.3 points, respectively.
Adverse events in the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial treating patients with severe back or knee/hip osteoarthritic pain were more commonly seen in the opioid group (P = 0.03) but this may not have been clinically significant. There are several limitations in this trial: the generalizability may be limited due to the study population (Veteran population, mostly male, current opioid users excluded) and it relied on subjective reporting by the patients.
Canadian Guideline for opioid therapy and chronic non-cancer pain adapted,
- Optimize nonopioid pharmacotherapy and nonpharmacologic therapy before trial of opioids
- For patients with persistent pain despite optimization and no history of substance misuse, consider a trial of opioids
- Avoid opioids in patients with active substance misuse
- Patients with active psychiatric disorder and persistent pain despite optimization, stabilize psychiatric disorder before trial of opioids
- Trial of opioids max dose should be restricting to less than 90 mg morphine equivalents daily
- Trial of opioids should be restricting to less than 50 mg morphine equivalents daily when initiating
- Patients with persistent pain or symptoms despite opioid therapy should have opioids rotated
- Patients should be tapered down to the lowest effective dose
- In patients unable to taper recommend multidisciplinary approach
- Single-center, blind outcome assessment, randomized trial
- Opioid (n=120)
- Non-opioid (n=120)
- Setting: 62 American primary care clinicians affiliated with the Veterans Affairs
- Enrollment: June 2013 to December 2015
- Mean follow-up: 12 months
- Analysis: Intention-to-treat
- Primary Outcome: Improvement in pain-related function assessed with the Brief Pain Inventory (BPI)
- Back pain or knee or hip pain associated with osteoarthritis
- current non-opioidanalgesic use
- Nearly every day ≥6 months
- ≥ 5 points on PEG scale
- Long term opioid treatment
- contraindications to all drug classes in either group
- conditions that could interfere with outcome assessment (e.g. life expectancy <12 months)
Opioid group displayed
- Demographics: Mean age 56.8 years, 13% female, 88% Causation, 6% African descent, 6% other ethnicity, University education 24%
- Employment: Employed 42%, Self-employed 6%, Retired 36%, other 16%
- Back pain 65%, Hip/knee osteoarthritis pain 35%
- Smoker 21%, Hazardous Ethanol use (AUDIT Score ≥8) 3%, Illicit drug use 7%
- Mental Health: moderate depression 23%, Moderate anxiety 9%, PTSD 21%
Step-wise apprach taken in both groups
- Opioid Group, titrated to maximum of 100 morphine-equivalent mg:
- Morphine IR, hydrocodone/acetaminophen, oxycodone IR
- morphine sustained release, oxycodone sustained release
- transdermal fentanyl
- acetaminophen and NSAIDs
- adjuvant oral medications (nortriptyline, amitriptyline, gabapentin), topical analgesics (capsaicin, lidocaine)
- Drugs requiring pre-authoirzation in VA system (pregabalin, duloxetine, tramadol)
Comparisons are Opioid therapy vs. Non-opioid therapy at 12 months.
- Pain-Related Function BPI Score
- 3.4 vs. 3.3 (Difference 0.1 [95% CI -0.5 to 0.7] P = 0.58)
- Functional response (≥ 30% in BPI)
- 59.0% vs. 60.7% (Difference -1.7% [95% CI -14.4 to 11.0] P = 0.79)
- Pain Intensity on BPI
- 4.0 vs. 3.5 (Difference 0.5 [95% CI 0.0 to 1.0] P = 0.03)
- Pain Intensity response (≥ 30% in BPI)
- 41.0% vs. 53.9% (Difference −12.8% [95% CI, −25.6 to 0.0] P = 0.05)
- VR-12 Physical Health (score 0-100, lower=worse)
- 32.7 vs. 33.9 (Difference −1.3 [95% CI −3.8 to 1.3] P = 0.23)
- VR-12 mental health (score 0-100, lower=worse)
- 51.2 vs. 50.4 (Difference 0.7 [95% CI −2.4 to 3.8] P = 0.04)
- RMDQ-11 pain-related physical function (range, 0-11; higher score = worse)
- 5.8 vs. 5.9 (Difference −0.1 [95% CI −1.0 to 0.8] P = 0.47)
- PHQ-8 depression symptoms (range, 0-24; higher score = worse)
- 4.3 vs. 4.5 (Difference −0.2 [95% CI −1.5 to 1.1] P = 0.13)
- GAD-7 anxiety symptoms (range, 0-21; higher score = worse)
- 2.5 vs. 2.8 (Difference −0.4 [95% CI −1.4 to 0.7] P = 0.02)
- PROMIS sleep disturbance (range, 8-32; higher score = worse)
- 23.4 vs. 21.0 (Difference 2.3 [95% CI 0.1 to 4.6) P = 0.33)
- MIDAS headache disability (range, 0-270; higher score = worse)
- 3.7 vs. 3.2 (Difference −0.5 [95% CI −2.7 to 3.6] P = 0.82)
- ASEX sexual function (range, 5-30; higher score = worse)
- 17.9 vs. 19.0 (Difference −1.1 [95% CI −2.8 to 0.7) P = 0.49)
- MFI general fatigue (range 4-20; higher = worse)
- 12.5 vs. 12.0 (Difference 0.6 [95% CI −0.6 to 1.7] P = 0.68)
- MFI mental fatigue (range 4-20; higher = worse)
- 9.2 vs. 9.3 (Difference 0.1 [95% CI −1.3 to 1.0] P = 0.39)
- MFI physical fatigue (range 4-20; higher = worse)
- 12.4 vs. 11.8 (Difference 0.7 [95% CI −0.5 to 1.9] P = 0.73)
- MFI reduced activity (range 4-20; higher = worse)
- 10.6 vs. 10.3 (Difference 0.3 [95% CI −1.0 to 1.5] P = 0.74)
- MFI reduced motivation (range 4-20; higher = worse)
- 8.6 vs. 8.8 (Difference −0.2 [95% CI −0.7 to 1.6] P = 0.09)
- Medication-related symptom checklist (score 0-19, higher = worse)
- 1.8 vs. 0.9 (Difference 0.9 [95% CI 0.3 to 1.5] P = 0.03)
- All-cause hospitalization, P = 0.94
- 0 = 83% vs. 83%
- 1 = 13% vs. 13%
- ≥2 = 5% vs. 4%
- All-cause ED visit, P = 0.18
- 0 = 50% vs. 61%
- 1 = 28% vs. 25%
- ≥2 = 22% vs. 14%
- Patients with Falls after enrollment, P = 0.19
- 0 = 53% vs. 53%
- 1 = 22% vs. 14%
- ≥2 = 25% vs. 33%
- Blinding not conducted
- Patient self-reporting may by affected by bias
- Generalizability limited due to VA population
- Patients using opioids excluded
- Merit Review Award (I01-HX-000671) from the US Department of Veterans Affairs Health Services Research and Development Service
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