What alternative therapies can be used to manage chronic refractory cough and back pain in a patient with impaired renal function who cannot tolerate gabapentin (Neurontin), pregabalin (Lyrica), or pregablin due to adverse effects?

Alternative Therapies for Chronic Refractory Cough and Back Pain When Gabapentinoids Are Not Tolerated

For chronic refractory cough in patients who cannot tolerate gabapentinoids, multimodality speech pathology therapy is the primary recommended alternative, with low-dose opiates (morphine 5 mg twice daily) reserved for severe cases when quality of life is substantially impaired; for back pain, tricyclic antidepressants are the first-line alternative medication. 1, 2

Management of Chronic Refractory Cough

First-Line Non-Pharmacologic Approach

Multimodality speech pathology therapy should be initiated as the primary treatment for refractory chronic cough when gabapentinoids cannot be used. 1

• This therapy includes patient education about cough mechanisms, cough suppression techniques, vocal hygiene training, and psychoeducational counseling 1
• The American College of Chest Physicians (CHEST) guidelines specifically recommend this approach for unexplained chronic cough with Grade 2C evidence 1
• Speech pathology therapy has demonstrated objective reductions in cough frequency and improvements in quality of life 1

Pharmacologic Alternative: Low-Dose Opiates

When speech pathology therapy fails and cough severely impacts quality of life, low-dose slow-release morphine (5 mg twice daily) should be considered. 1

• A randomized controlled trial demonstrated significant quality of life improvement with morphine, showing a mean increase of 3.2 points in Leicester Cough Questionnaire scores 1
• The most common side effects are constipation and drowsiness, but the medication was well tolerated with no withdrawals due to adverse events in the trial 1
• CHEST guidelines recommend reassessing benefits and risks at 1 week, then monthly before continuing opiate therapy 1

Important caveat: While opiates narrowly failed the 80% guideline acceptance voting threshold for unexplained cough, the CHEST panel specifically endorsed their use for interstitial lung disease-associated cough when alternative treatments have failed and quality of life is substantially affected 1

Additional Considerations for Cough Management

• Assess for GERD-related symptoms, as resolution of GERD can lead to clinically significant improvement in cough (mean LCQ improvement from 14.3 to 17.9) 1
• Do not prescribe proton pump inhibitors if workup for acid reflux is negative (Grade 2C recommendation) 1
• Do not prescribe inhaled corticosteroids if tests for bronchial hyperresponsiveness and eosinophilia are negative (Grade 2B recommendation) 1

Management of Back Pain

First-Line Medication Alternative

Tricyclic antidepressants (TCAs) are the recommended first-line alternative to gabapentinoids for chronic low back pain. 2

• The American College of Physicians recommends TCAs as effective for pain relief with established efficacy and fewer central nervous system side effects than gabapentinoids 2
• Start with low doses (10-25 mg) at bedtime, particularly in older adults, and titrate slowly 2
• Amitriptyline or nortriptyline are appropriate choices 2

Critical safety considerations for TCAs:

• May cause anticholinergic side effects, sedation, and cardiac conduction abnormalities 2
• Use with caution in elderly patients or those with cardiac disease 2
• These risks must be weighed against the patient's renal function impairment, as TCAs may be safer than renally-cleared alternatives

Additional Medication Options for Back Pain

NSAIDs are appropriate for both acute and chronic low back pain, particularly when inflammatory components are present. 2

• Consider topical NSAIDs, lidocaine, or capsaicin for localized back pain, especially in older adults, due to favorable safety profiles 2
• This is particularly relevant given the patient's impaired renal function, as topical formulations minimize systemic exposure

Skeletal muscle relaxants can be considered for short-term relief of acute exacerbations. 2

• Tizanidine is preferred due to better evidence 2
• Associated with central nervous system adverse effects, primarily sedation 2
• Avoid carisoprodol (metabolized to meprobamate with abuse risk), avoid dantrolene (black box warning for hepatotoxicity), and monitor for reversible hepatotoxicity with tizanidine and chlorzoxazone 2

Opioid analgesics or tramadol are second-line options only for severe, disabling pain. 2

• Use judiciously due to substantial risks including potential for abuse 2
• Reserve for cases not controlled with first-line options 2

Medications to Avoid for Back Pain

Do not prescribe SSRIs or trazodone for low back pain, as they have not been shown to be effective. 2

Treatment Algorithm

For Chronic Refractory Cough:

1. Initiate multimodality speech pathology therapy 1
2. Evaluate and treat GERD if symptoms present 1
3. If inadequate response after 4-6 weeks and quality of life severely impaired, add low-dose slow-release morphine (5 mg twice daily) 1
4. Reassess at 1 week, then monthly if continuing opiates 1

For Back Pain:

1. For chronic low back pain without radiculopathy: Start TCA (amitriptyline or nortriptyline 10-25 mg at bedtime), titrate slowly 2
2. For acute low back pain: Consider short-term skeletal muscle relaxant (tizanidine preferred) or NSAID if no contraindications 2
3. Consider topical analgesics (NSAIDs, lidocaine, capsaicin) for localized pain, especially given renal impairment 2
4. Add non-pharmacological therapies: spinal manipulation for acute pain; exercise therapy, acupuncture, massage, yoga, or cognitive-behavioral therapy for chronic pain 2
5. Assess response after 4-6 weeks at stable doses 2
6. If inadequate control, consider referral for further evaluation 2

Monitoring and Follow-Up

• For cough: Monitor quality of life using validated tools; if using opiates, reassess risk-benefit at 1 week and monthly 1
• For back pain: Assess response after 4-6 weeks; monitor for TCA side effects (anticholinergic effects, sedation, cardiac effects) 2
• Given impaired renal function, avoid medications requiring renal clearance and monitor closely for drug accumulation 2