What additional medications can be added to pregabalin (an anticonvulsant) for a patient with radicular pain who is already on pregabalin?

Additional Medications for Radicular Pain in Patients Already on Pregabalin

Consider adding a tricyclic antidepressant (nortriptyline) or an extended-release opioid (morphine or oxycodone) to pregabalin for improved pain control, as combination therapy has demonstrated superior efficacy compared to monotherapy in neuropathic pain conditions. 1

Evidence-Based Combination Therapy Options

First-Line Addition: Tricyclic Antidepressants

• Nortriptyline combined with pregabalin's related compound gabapentin was superior to either medication alone in randomized controlled trials, suggesting this combination strategy may work with pregabalin as well 1
• This combination targets different neurotransmitter systems—pregabalin modulates calcium channels while tricyclics affect norepinephrine and serotonin reuptake—providing mechanistic rationale for additive benefit 1
• Start nortriptyline at low doses (10-25 mg at bedtime) and titrate gradually to minimize anticholinergic side effects, particularly in elderly patients 1

Second-Line Addition: Extended-Release Opioids

• Extended-release morphine combined with gabapentin required lower dosages of both medications and resulted in better pain relief than either alone in patients with postherpetic neuralgia and painful diabetic neuropathy 1
• Extended-release oxycodone added to existing gabapentin treatment showed generally consistent results in painful diabetic neuropathy 1
• An open-label study of 403 neuropathic pain patients found that extended-release oxycodone plus pregabalin improved pain relief at lower dosages than either medication alone, with improved quality of life and better tolerability 1

Important Caveat About Low-Dose Opioids

• One trial showed no additional benefit of low-dose oxycodone (10 mg/day) versus placebo when combined with pregabalin 1
• This suggests that if opioids are added, they must be titrated to adequate analgesic doses rather than using minimal doses

Alternative Combination Options

Topical Lidocaine 5%

• Pregabalin combined with topical 5% lidocaine has been studied in randomized trials, providing localized pain relief without systemic side effects 1
• This is particularly useful for well-localized radicular pain with cutaneous hyperalgesia
• Can be applied directly to the painful dermatome without concern for drug-drug interactions 2

Duloxetine (SNRI)

• While not specifically studied in combination with pregabalin for radicular pain, duloxetine showed small but significant effects (0.60-0.79 point reduction on 0-10 scale) for chronic low back pain 1
• Evidence for duloxetine in radicular pain specifically is insufficient (only one small trial with 25 patients) 1
• Duloxetine increases risk of nausea and withdrawal due to adverse events (odds ratio 2.72) 1

What NOT to Add

Avoid Adding Gabapentin to Pregabalin

• Both medications have identical mechanisms of action and adverse effect profiles—adding gabapentin to pregabalin would simply increase the sedative burden without additional benefit 3
• Pregabalin and gabapentin do not interact pharmacokinetically, but their pharmacodynamic effects are additive, particularly for dizziness, somnolence, and fall risk 2

Systemic Corticosteroids Are Not Effective

• Six trials consistently found no differences between systemic corticosteroids and placebo for radicular low back pain 1
• Oral prednisone increased risk of adverse events (49% vs 24%), insomnia (26% vs 10%), and nervousness (18% vs 8%) 1

Pregabalin Dose Escalation May Be Insufficient

• For chronic radicular back pain specifically, pregabalin showed no effects on pain intensity versus placebo in two fair-quality trials (differences only 0.14-0.21 points on 0-10 scale) 1
• This contrasts with pregabalin's proven efficacy in postherpetic neuralgia and diabetic neuropathy, suggesting radicular pain may be a relatively refractory condition 1
• One small trial (n=19) found pregabalin no more efficacious than placebo for lumbar and cervical radicular pain 4

Critical Clinical Pitfalls

Lumbosacral Radiculopathy May Be Treatment-Resistant

• A randomized crossover study of morphine, nortriptyline, and their combination in lumbosacral radiculopathy failed to show benefit of either the combination or medications alone 1
• This suggests that radicular pain, particularly lumbosacral radiculopathy, may be a relatively refractory chronic pain condition compared to other neuropathic pain types 1

Monitor for Additive Sedation

• Combination therapy with pregabalin plus opioids or tricyclics increases risk of sedation, dizziness, and falls 1
• Serious breathing problems can occur when pregabalin is combined with opioid pain medications, benzodiazepines, or other CNS depressants 5
• Start with lower doses of the added medication and titrate slowly while monitoring for excessive sedation

Ensure Adequate Pregabalin Dosing First

• Before adding another medication, verify the patient is on an adequate pregabalin dose (300-600 mg/day) for at least 2-4 weeks 5
• Higher pregabalin doses (up to 600 mg/day) result in significantly greater pain reduction, with many patients responding to dose escalation who did not respond to lower doses 6
• The optimal benefit-to-risk ratio is typically achieved at 300 mg/day, with 600 mg/day reserved for patients with inadequate response who tolerate the medication well 5