Offering insights and perspectives on prescribing medication for patients with painful wounds, these expert panelists discuss drugs for neuropathic pain, extended-release narcotics and how to be wary of pain medication “seekers.”
“I would estimate that not a day goes by in which I have not prescribed antinociceptive therapy for neuropathic pain,” says Allen Jacobs, DPM.
Most frequently, Dr. Jacobs utilizes gabapentin or amitriptyline. He emphasizes the importance of remembering that these drugs may be helpful in resolving symptoms such as paresthesia or dysesthesia, but do not interdict the actual progression of the disease process. One typically initiates these agents at a lower dose, he says, gradually titrating them until patients achieve pain relief or side effects require discontinuation. Frequently, symptomatic neuropathic symptoms occur during the evening hours, in which case Dr. Jacobs has the patient use the medication one hour prior to bedtime.
It is important to evaluate and document the patient’s response to therapy and any potential side effects, stresses Dr. Jacobs. With gabapentin, he says neuropsychiatric adverse sequelae are most worrisome. With the tricyclic antidepressants (amitriptyline and nortriptyline), serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine (Effexor, Pfizer), he will check for and document fluid retention, anticholinergic side effects, weight gain, dysrhythmia and other side effects.
Eric Lullove, DPM, uses both gabapentin and pregabalin for neuropathic pain although he notes that gabapentin never received FDA approval for neuropathic pain. Likewise, Kazu Suzuki, DPM, CWS, points out that gabapentin also works well for any other type of pain condition despite its off-label FDA status. Many anesthesiologists and pain management doctors are using such “nerve pain” medications for many pain conditions, says Dr. Suzuki, even though patients may not have diabetes or neuropathic conditions, for which gabapentin has been in use traditionally.
Leon Brill, DPM, CWS, generally starts neuropathic patients on gabapentin 300 mg tid and titrates the dose up to their level of comfort. He will use pregabalin 75 to 150 mg bid as well but finds that patients seem to tolerate gabapentin better in regard to side effects and the drug is more cost-effective. He uses duloxetine 60 mg daily for neuropathic pain, finding it to be most effective in patients who seem to exhibit depressive symptoms.
For Dr. Lullove, loading doses of pregabalin usually start around 75 mg daily, duloxetine doses start at 30 mg daily and gabapentin doses start at 100 mg twice daily. Dr. Suzuki will prescribe gabapentin 100 mg qhs (before bedtime) to start, gradually increasing the dosage until the patient experiences acceptable pain relief. He notes the common side effect of gabapentin is drowsiness, which works well for his patients with pain and sleep problems because of chronic pain.
“I specifically tell patients when starting these medications that drowsiness and lethargy are the primary side effects, mostly in the first three to five days of starting the medication,” says Dr. Lullove. “It is important to communicate to the patients the need to not drive immediately within one to two hours of taking the loading doses of the medications.”
In regard to other medications for the treatment of painful neuropathy, Dr. Brill will prescribe amitriptyline 25 mg at bedtime for patients whose primary pain is at bedtime. Other medications include local treatment with doxepin cream 5% (Zonalon, PharmaDerm) applied topically bid. On occasion, he will use lidocaine patches.
“I find more often than not I use a combination of these medications to achieve a level of acceptable comfort,” says Dr. Brill.
The SNRIs, such as duloxetine or venlafaxine, are Dr. Suzuki’s second choice for neuropathic pain or as an adjuvant pain medication if the patient fails or is allergic to gabapentin or pregabalin. He notes that duloxetine now has a FDA indication for “chronic musculoskeletal pain,” although he says the black box warning for an increased propensity for suicide is an issue. Dr. Suzuki believes physicians used to prescribe tricyclic antidepressants such as amitriptyline often for diabetic neuropathic pain, but he almost never prescribes tricyclics because the side effects (such as dry mouth) are often intolerable in comparison to the mild drowsiness patients often encounter with gabapentin.
The topical application of adjunctive analgesics is very helpful for some patients and avoids problems of drug interactions and side effects that Dr. Jacobs notes can frequently lead to a reluctance to prescribe similar medications orally. He says gabapentin, ketamine, clonidine (Catapres, Boehringer Ingelheim), lidocaine (Lidoderm, Endo Pharmaceuticals), bupivacaine and other agents are useful in the management of symptomatic neuropathy. Dr. Jacobs notes that one may apply them as a compounded cream with very successful clinical results in many circumstances.
Dr. Jacobs advises remembering at all times that the anticonvulsants, antidepressants and other adjuvant analgesics utilized for symptomatic diabetic neuropathy are for relief of sensory symptoms and do not treat or reverse entrapment neuropathy, autonomic neuropathy or motor neuropathy. He adds that such agents do not reverse the ischemia, oxidative or nitrosative stress causing the neuropathy.
“We must remember that diabetic neuropathy is a metabolic disorder and correction requires metabolic correction,” says Dr. Jacobs. “I explain this to patients in detail and always combine agents such as anticonvulsants or antidepressants with supplements to reverse oxidative stress and assist in actual correction of the disease process.”
Common supplements for Dr. Jacobs include L-methylfolate, pyridoxal 5’ phosphate, methylcobalamin (Metanx, Pamlab) with adjuvant analgesics. He also will use alpha lipoic acid, L-carnitine and inositol.
Dr. Suzuki acknowledges some data showing that oral supplements of folic acid and alpha lipoic acid provide “meaningful” pain relief in diabetic neuropathy.1 However, he says those supplements would be the second line of treatment after gabapentin since it reportedly takes a few weeks of supplement use before patients can feel any pain relieving effect.2
“I know some neurologists swear by the topical capsaicin cream (Zostrix) for diabetic neuropathy but I haven’t had good luck getting the patients to apply it multiple times per day,” points out Dr. Suzuki.
For the most part, if Dr. Lullove needs to use extended-release medications, he will always try to minimize the amount needed for the longest time. As he notes, the goal should be to sustain steady state levels in the blood so the patient does not have the peaks and troughs associated with conventional opioid medications. Ideally, he suggests matching the dosing schedules with the American Academy of Pain Management’s criteria for extended-release medications. Dr. Lullove notes that sometimes, the need for a “breakthrough” pain medication is necessary when using extended-release opioids due to the slow time release nature. Either way, Dr. Lullove says careful management and follow-up is necessary, and one should see patients no less than weekly in the first month of therapy during management.
Dr. Jacobs has found several opioid and opioid-like agents very helpful for the management of symptomatic diabetic neuropathy. Tapentadol (Nucynta, Janssen Pharmaceuticals) has recently received approval for the treatment of diabetic neuropathy. He notes that tramadol, with mu-2 receptor activity and some tricyclic activity, is also helpful to manage symptomatic neuropathy. He cites studies indicating that oxycodone is helpful for the management of neuropathic pain.3
As is the case with adjuvant analgesics, Dr. Jacobs will personally insist on good control of diabetes and evaluate the patient for entrapment neuropathy. He utilizes agents such as Metanx to reverse the actual disease process before considering opioid analgesics for the management of symptomatic neuropathy. Dr. Jacobs advises that patients must understand that concurrent treatment of the oxidative and nitrosative stress causing the neuropathy is essential in addition to the use of opioids for the management of symptoms.
“The chronic use of opioids for pain management is an arena in which not all podiatric physicians are comfortable. This is understandable,” says Dr. Jacobs. “However, there are patients who require these medications and should not be made to suffer from pain, lack of restorative or restful sleep, or decreased quality of life because of our fears associated with such medications.”
Dr. Jacobs adds that one may consider alternatives such as spinal cord modulation, sequential peripheral nerve blockades, peripheral nerve release or the referral of the patient to a pain management specialist.
Dr. Brill does not use oxycodone but does use hydrocodone and tramadol. He has no problem prescribing opioids and other analgesics but says if those medications fail to alleviate patients’ pain to an acceptable level, he will refer them to a pain management specialist for more aggressive treatment.
Dr. Suzuki has not had many problems with patients who may or may not abuse opioids, such as those who ask for too many tablets. Instead, he has had more problems with pharmacies refusing to dispense these medications because they are either “out of stock” or they suspect drug abuse, rightfully or not.
“Since more and more pharmacies are connected electronically for e-prescribing capability, I think it is easier to spot potential ‘drug seekers’ who may do doctor shopping for pain medications,” says Dr. Suzuki. “We always instruct our residents to believe the patient’s report of pain, and it is against our institution’s policy to prescribe ‘placebo’ pills to see if the pain is ‘real’ or not.”
When patients require chronic opioid use, Dr. Jacobs will document clearly that he has discussed with the patient the potential for addiction, tolerance and adverse systemic sequelae to the medications. He documents the pain requiring such medication in detail and documents that he instructed the patient to carefully read all of the printed materials that typically will accompany the prescription at the pharmacy. Finally, his patients must enter into a “pain management contract,” a consent form in which they agree not to abuse the medications, not to receive opioid analgesics elsewhere and limit the quantity per month.
Having an open wound is an inherently painful condition and Dr. Suzuki has not had too many “pain medication” seekers who caused a lot of problems. Occasionally, he does require a “contract” if a single patient asks for multiple refills of narcotic medications or his practice will sometimes require patients to get a consultation and receive supervision with pain management specialists before his office provides prescriptions.
As Dr. Brill notes, pain medication seekers are a potential problem in any medical practice. He acknowledges that it sometimes can be very challenging to identify a potential abuser versus someone who is truly in need and not responding to the medical regimen.
The best way to combat drug seekers, suggests Dr. Lullove, is to take a thorough history, log onto the national database to check for potential abusers, and make all the patients of your practice sign a “narcotic consent and agreement use policy.” The true pill seekers will never sign the agreement, he says, since they don’t want to be held accountable for getting medications from one sole provider. As he adds, the policy also protects the practice from potential abuse by making sure that patients for whom you have prescribed medications can only refill and renew with your practice. He also emphasizes the need for closer internal control over prescription pads. Dr. Lullove emphasizes making sure the pads are under lock and key during the day, and are not left in a drawer for theft potential.
If and when Dr. Jacobs suspects drug-seeking behavior, his response is to refer such patients to pain management “pure and simple. There is no negotiation on this matter.”
“Every practicing physician with a DEA diversion license should worry about ‘seekers,’” says Dr. Lullove.
Dr. Brill is the President of the BrillStone Corporation in Dallas. He is a Fellow of the American College of Foot and Ankle Surgeons, and is also a consultant in wound care and reconstructive foot and ankle surgery at the Wound Care Clinic at Presbyterian Hospital in Dallas.
Dr. Jacobs is a Fellow of the American College of Foot and Ankle Surgeons, and a Fellow of the American Professional Wound Care Association. He is in private practice in St. Louis.
Dr. Lullove is in private practice in Boca Raton and Delray Beach, Fla. He is a Staff Physician at West Boca Medical Center in Boca Raton. Dr. Lullove is a Fellow of the American College of Certified Wound Specialists.
Dr. Suzuki is the Medical Director of the Tower Wound Care Center at the Cedars-Sinai Medical Towers. He is also on the medical staff of the Cedars-Sinai Medical Center in Los Angeles and is a Visiting Professor at the Tokyo Medical and Dental University in Tokyo.
1. Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with a-lipoic acid over 4 years in diabetic polyneuropathy. Diabetes Care. 2011; 34(9):2054-2060.
2. Ziegler D, Ametov A, Barinov A. Oral treatment with a-lipoic acid improves symptomatic diabetic polyneuropathy. Diabetes Care. 2006; 29(11):2365-70.
3. Hermanns K, Junker U, Nolte T. Prolonged-release oxycodone/naloxone in the treatment of neuropathic pain - results from a large observational study. Expert Opin Pharmacother. 2012; 13(3):299-311.
For further reading, see “A Guide To Pain Management In Wound Care” in the November 2012 issue of Podiatry Today, “Choosing Medications For Painful Diabetic Neuropathy” in the July 2003 issue or “Case Studies In Painful Diabetic Neuropathy” in the August 2006 issue.