There are a variety of different types of medications that can be used to treat neuropathic pain.
Many of the medications are antiseizure or antidepressant medications.
The treatment of neuropathic pain with pharmacologic interventions can lead to substantial pain relief when dosed correctly, but the adverse effects from these medications can prevent patients from reaching their therapeutic dose.
Many classes of medications are thought to be effective and are evidence based for neuropathic pain. These include antiseizure and antidepressant medications, which may work in both the central and peripheral nervous systems. Class, initial dosing, and dosing of medications researched for effectiveness in treating neuropathic pain are detailed in Tables 34-1 and 34-2. There is also evidence that combination therapy, from multiple classes, is more efficacious than placebo or the single medication by itself. For example, there is evidence that opioids or TCAs combined with gabapentinoid medications are more effective than either medication alone for painful diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN).1 Dosages for combinations medication therapies may be lower than usual, which will also decrease side effects.
ANTISEIZURE MEDICATIONS
Medications typically considered “antiseizure” treatments act as sodium channel blockers or calcium channel blockers or both. Sodium channel blockers inhibit initiation, maintenance, and propagation of neural discharges. Medications such as carbamazepine and local anesthetics such as lidocaine are examples of sodium channel blockers. Calcium channel blockers, such as gabapentin, bind to the alpha 2 delta subunit of L-type calcium channel, which causes decreases in glutamate and substance P and increases norepinephrine and GABA in pain pathways. Both sodium and calcium channel blockers have known efficacy in the treatment of neuropathic pain.2
Topiramate is FDA approved for the treatment of seizures and migraine prophylaxis. This medication has been used for bipolar disorder, weight loss, eating disorders, alcohol and drug dependence, headaches, posttraumatic stress disorder (PTSD), DPN, PHN, and complex regional pain syndrome (CRPS). The mechanism of action involves both the sodium and calcium channels to enhance GABA activity. Side effects of nephrolithiasis and ocular glaucoma are related to its effects as a carbonic anhydrase inhibitor, which lowers bicarbonate and should be monitored with electrolytes. Other effects included weight loss, sedation, and metabolic acidosis. Patients on topiramate and some other antiepileptic drugs (AEDs) need to be counseled regarding the potential for fetal birth defects.3 Bicarbonate levels and liver function tests may also need to be assessed during treatment.
Carbamazepine is FDA approved for seizures, trigeminal neuralgia (TN), and bipolar disorder. There is evidence for efficacy in PHN, DPN, and poststroke pain.4 Carbamazepine selectively blocks abnormally active C fibers and A delta fibers through voltage-gated sodium channels. Additionally, it acts as a GABA agonist and works both peripherally and centrally. Side effects include Stevens-Johnson syndrome, aplastic anemia, or other changes in the hematopoietic system, ataxia, dizziness, bitemporal heminanopsia, hormonal abnormalities, lipid abnormalities, and toxic epidermal necrolysis.5 Oxcarbazepine, a structural variant of carbamazepine, has less side effects and is better tolerated.6 This alternative is FDA approved for seizures and bipolar disorder and its main side effect is hyponatremia. These medication therapies should be monitored with electrolytes, blood counts, and liver function tests before initiation and then with subsequent periodic follow-up.
TABLE 34-1 Efficacy of Medications for Neuropathic Pain Conditions
+ = ≥1 Trial showed statistically significant pain relief for the primary outcome compared with placebo.
− = ≥1 Trial showed no statistically significant pain relief for the primary outcome compared with placebo.
n/a= unavailable data.
Lamotrigine is FDA approved for bipolar disorder and seizures. It is used for treatment of TN, DPN, polyneuropathy, and central pain.7 This medication’s proposed mechanism of action includes sodium channel blockade that prevents the release of glutamate. The side effect profile includes rash and Stevens-Johnson syndrome, blood dyscrasias, dermatitis, alopecia, nausea, and vomiting. The medication needs to be discontinued immediately for patients who present with a rash.
Local anesthetics are commonly used to treat neuropathic pain and are available in multiple formulations such as lidocaine ointments or creams and lidocaine transdermal patches. As a sodium channel blocker, lidocaine is the most commonly available local anesthetic for pain management. Pain conditions treated with lidocaine include PHN, meralgia parasthetica, intercostal neuralgia, and postthoracotomy neuralgia. There is evidence that intravenous application of lidocaine can be effective for neuropathic pain conditions such as TN, chemotherapy-induced neuropathy, PHN, DPN, and postoperative pain through repeated treatments.8 The intravenous application of lidocaine is typically done at specialized pain centers.
Gabapentin is FDA approved for PHN, seizure, and restless legs syndrome, whereas pregabalin is FDA approved for DPN, PHN, partial onset seizures, and fibromyalgia. These medications bind voltage-gated calcium channels that modify firing of neurons and cause release of GABA.9 Side effects for gabapentin include somnolence, dizziness, nausea, edema, and myoclonus. Side effects for pregabalin are similar and include somnolence, dizziness, dry mouth, altered mentation, weight gain, blurry vision, constipation, and swelling. The main differences between gabapentin and pregabalin are in the pharmacodynamics and pharmacokinetics. Gabapentin has a nonlinear pharmacokinetic profile, is variably absorbed in the gastrointestinal system, and is less bioavailable at higher doses. In contrast, pregabalin has a linear profile and is well absorbed with consistent bioavailability across dosages.9 Clinical effects from gabapentin are achieved at higher doses, whereas benefits from pregabalin might be discerned quicker. Neither medication has drug-drug interactions nor effects on the liver or kidneys but must be renally dosed in those with kidney disease.2 Both pregabalin and gabapentin are first-line treatments for neuropathic pain.10 Gabapentin at doses between 1800 and 3600 mg is effective for pain from PHN and diabetic neuropathy.4 Pregablin is thought to provide pain relief at doses of 300, 450, and 600 mg.11 Side effect profiles for these medications may limit use.
TABLE 34-2 Neuropathic Pain Medication Effective Dosages and Indications
DRUG CLASS
MEDICATION
EFFECTIVE DOSAGE
INDICATION
TCAs
Nortriptyline Desipramine
25 mg to start to 150 mg/d
Central and peripheral NP
SNRI
Duloxetine
60-120 mg/d
DPN, musculoskeletal pain
SNRI
Venlafaxine
37.5 mg-225 mg/d or bid
DPN
Multiple mechanisms including calcium channel inhibition
Pregabalin
75-600 mg/d in divided doses tid or bid
DPN, PHN, SCI
Multiple mechanisms including calcium channel inhibition
Gabapentin
300-3600 mg/d in divided doses tid
DPN, PHN, cancer-related neuropathy
Multiple mechanisms including calcium channel inhibition
Extended release gabapentin
300-1800 mg/d
PHN
Multiple mechanisms including sodium channel blocker
Carbamazepine
100-800 mg/d in divided doses
TN
Sodium channel blocker
Lidocaine patch
1-3 patches per day, 12 h on and 12 h off
PHN
TRPV1 channel agonist
Capsaicin patch
1 patch to the painful area for 30-60 min every 3 mo
