From the Guidelines
For chronic pain that has not responded to NSAIDs and gabapentinoids, a multimodal approach is recommended, prioritizing non-pharmacological interventions and considering tricyclic antidepressants, SNRIs, and topical treatments. Consider trying tricyclic antidepressants like amitriptyline (starting at 10-25mg at bedtime, gradually increasing to 50-150mg as tolerated) or SNRIs such as duloxetine (30-60mg daily) or venlafaxine (75-225mg daily) 1. Topical treatments can be helpful for localized pain, including lidocaine patches (5%, applied for 12 hours daily) or capsaicin cream (0.025-0.075%, applied 3-4 times daily) 1.
Non-Pharmacological Interventions
- Physical therapy
- Cognitive behavioral therapy
- Mindfulness meditation are crucial non-pharmacological approaches that should be incorporated into any treatment plan 1.
Pharmacological Interventions
- Low-dose naltrexone (1-4.5mg daily) may benefit some patients by modulating immune function and reducing inflammation
- Referral to a pain specialist may be necessary to consider interventional procedures like nerve blocks, radiofrequency ablation, or in carefully selected cases, opioid therapy with close monitoring 1.
This multimodal approach targets different pain pathways simultaneously, increasing the likelihood of meaningful pain reduction while minimizing side effects from any single treatment. The most recent and highest quality study 1 supports the use of a multimodal approach, emphasizing the importance of non-pharmacological interventions and careful consideration of pharmacological options.
From the FDA Drug Label
Study CLBP-3: Four hundred and one patients were randomized to receive fixed doses of duloxetine delayed-release capsules 60 mg daily or placebo (N=198 on duloxetine delayed-release capsules, N=203 on placebo), and 303 (76%) completed the trial. Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain) After 12 weeks of treatment, patients taking duloxetine delayed-release capsules 60 mg daily had significantly greater pain reduction compared to patients taking placebo. Study OA-1: Two hundred fifty-six patients (N=128 on duloxetine delayed-release capsules, N=128 on placebo) enrolled and 204 (80%) completed the trial Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). After 13 weeks of treatment, patients taking duloxetine delayed-release capsules had significantly greater pain reduction than patients taking placebo.
The best ways to treat chronic pain in someone who has failed NSAIDs and gabapentinoids may include:
- Duloxetine 60 mg daily, as it has shown significant pain reduction in patients with chronic low back pain and osteoarthritis 2
- Starting with a dose of 30 mg once daily for one week, then increasing to 60 mg once daily, and potentially increasing to 120 mg once daily for patients with sub-optimal response to treatment 2 Key points to consider:
- Duloxetine has been shown to be effective in reducing pain in patients with chronic low back pain and osteoarthritis
- The recommended dose is 60 mg daily, with potential increases to 120 mg daily for patients with sub-optimal response to treatment
- Patients who did not respond to NSAIDs may still benefit from duloxetine treatment 2
From the Research
Treatment Options for Chronic Pain
When NSAIDs and gabapentinoids are no longer effective, there are alternative treatment options available.
- Antidepressants, such as tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors, have been shown to be effective in treating chronic pain, particularly neuropathic pain, headaches, low back pain, fibromyalgia, and irritable bowel syndrome 3, 4, 5.
- These antidepressants work by increasing noradrenaline levels in the spinal cord, which inhibits chronic pain through α₂-adrenergic receptors 4, 5.
- Histone deacetylase inhibitors and antidepressants may also restore the impaired noradrenergic descending inhibitory system, which is often impaired in chronic pain states 4.
Pharmacological Treatments
The latest recommendations for pharmacological treatments of neuropathic pain include:
- First-line treatments: tricyclic antidepressants (e.g., amitriptyline), serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine), pregabalin, and gabapentin 6.
- Second-line treatments: lidocaine plasters, capsaicin high-concentration patches, and tramadol 6.
- Third-line treatments: strong opioids and botulinum toxin A 6.
Comparative Effectiveness
A study comparing the effectiveness of gabapentinoids and opioids in older patients with chronic pain found that gabapentinoids were associated with a larger reduction in chronic pain than opioids, with a larger effect at higher gabapentinoid dosages 7.