First-line treatment of diabetic peripheral neuropathic pain includes tricyclic antidepressants (e.g., RODGERS, MD, VINCENT SAVATH, MD, AND KEVIN HETTINGER, MD). Peripheral neuropathy is a common complication of diabetes mellitus, occurring in 30 to 50 percent of patients with the disease.1 It involves loss of sensation in a symmetric distribution between socks and gloves, which begins on the toes and progresses proximally. Approximately 10 to 20 percent of patients with diabetes have diabetic peripheral neuropathic pain, which is severe burning, tingling, or discomfort that worsens at night.1,2 Patients with diabetic peripheral neuropathic pain may also experience allodynia and hyperalgesia. Diabetic peripheral neuropathic pain interferes with sleep quality, mood and the level of activity.
Initial treatment goals include controlling hyperglycemia, which can acutely worsen pain. 3 While total relief is ideal, pain reduction of only 30 to 50 percent can be expected in most patients taking maximum doses of medication 4,5 The available evidence on the treatment of diabetic peripheral neuropathic pain is limited to small studies and few comparative trials. Although the American Society of Pain Educators has published consensus treatment guidelines, they offer little guidance on choosing a first-tier agent.6,7 Figure 1 presents a treatment algorithm for diabetic peripheral neuropathic pain based on available evidence.4 There are five main classes of medications and some alternative options used to treat diabetic peripheral neuropathic pain. Table 1 shows the doses, costs and quantities needed to treat (NNT) of selected drugs, 5,8—29 Table 2 lists common adverse drug effects, 5,8—11,14,18—20,30 Studies on medications used to treat diabetic peripheral neuropathic pain evaluate efficacy primarily by measuring pain reduction.
Few studies have examined the effects of diabetic peripheral neuropathic pain on quality of life. However, one study used the Nottingham Health Profile, a validated quality of life questionnaire, to examine quality of life in patients with diabetic peripheral neuropathic pain 31. The study showed a decrease in quality of life in areas of sleep, energy and exercise tolerance, as well as an increase in emotional reactivity, suggesting considerable benefits for treating diabetic peripheral neuropathic pain. Tricyclic antidepressants (TCAs) are recommended as first-line treatment for diabetic peripheral neuropathic pain in appropriate patients, although their mechanism of action is uncertain. For years, doctors have been using antivirals, such as amitriptyline and nortriptyline (Pamelor), to treat neuropathic pain, without approval from the U.S.
Food and Drug Administration (FDA) its labeling. A Cochrane review examined 12 studies with 404 participants with various types of neuropathic pain. The review found an NNT of 2.5 for achieving moderate pain relief with carbamazepine. 12 Adverse effects included drowsiness, dizziness, constipation, nausea, and ataxia.
12 Laboratory monitoring is important to consider when prescribing carbamazepine. Before starting treatment, the patient's blood levels of urea nitrogen, creatinine, transaminases and iron should be monitored, and a complete blood count (including platelets), a reticulocyte count, a liver function test and a urinalysis should be performed. It is also recommended to perform a lipid analysis and measure drug levels every six to 12 months.37,38 In addition, carbamazepine contains a warning for serious dermatological reactions, such as toxic epidermal necrolysis and Stevens-Johnson syndrome.37 The risk increases 10-fold in combination with human leukocyte antigen B*1502, which occurs almost exclusively in Asian people. Physicians should perform genetic testing before starting carbamazepine in this population, 12 Due to the need for laboratory monitoring and the risk of drug interactions, newer anticonvulsants are preferred to carbamazepine, 12 Valproate and phenytoin have not been as thoroughly researched as carbamazepine, but they have many of the same drawbacks, 4,6,39 Phenytoin has the additional complication of raising glucose levels, causing its use in patients with peripheral neuropathic pain diabetic, 9 common topical treatments for diabetics Peripheral neuropathic pain includes capsaicin cream (Zostrix) and 5% lidocaine patches (Lidoderm). Capsaicin stimulates C fibers to release and then exhaust substance P.
Many patients who take capsaicin experience a stinging sensation during the first week of treatment, which dissipates with continued use. In a meta-analysis carried out in 2004, in which six trials with 656 patients participated, it was found that capsaicin had an NNT of 6.4 and 5.7, which reduced pain by 50 percent at four and eight weeks, respectively; 19 lidocaine patches at 5% block neural sodium channels. Small efficacy trials have been conducted with this medication. A randomized controlled trial conducted in 2003 revealed that an NNT of 4.4 reduces pain by 50 percent.
20 The adverse effects are mainly dermatological and disappear when the patch is removed. The main advantage of topical treatment is that it can be added to systemic treatment at any time. As with many chronic diseases that interfere with quality of life, patients with diabetic peripheral neuropathic pain can explore complementary and alternative medicine (CAM) options. Complementary and alternative medicine therapies are being applied to diabetic peripheral neuropathic pain, although data are limited.
Asking patients about the complementary and alternative medicine treatments they use can help doctors provide more comprehensive patient care. The most promising complementary and alternative medicine therapies include l-carnitine and alpha-lipoic acid, which are available without a prescription. Early studies have shown positive results, but more long-term data are needed. 22,45 Data related to acupuncture are limited.
However, a pilot study and a small RCT have shown promise, 24,25 A Cochrane review is currently under way, 26 Due to the complicated drug interaction profiles of medications used to treat diabetic peripheral neuropathic pain (table 34), it is advisable to exhaust monotherapy options before considering combination therapy, with the exception of topical agents. Few studies have considered the role of combination therapy, although one study showed a lower need for opiates when combined with gabapentin, 15 If combination therapy is necessary, doctors should consider the mechanism of action when choosing medications and consider consulting a pain management specialist.7 It is important to avoid combining ATCs with SSRIs or SNRIs to avoid serotonin syndrome, a potentially fatal condition with autonomic and neurological symptoms, 47 Before starting the treatment, doctors should thoroughly review drug lists for possible interactions in patients with comorbidities. Drugs that may interact with treatments for peripheral neuropathic pain in diabetics include statins, beta-blockers, sulfonylureas, levothyroxine, warfarin (Coumadin) and chain diuretics. Drug interactions are primarily due to liver metabolism through the cytochrome P450 system or to a drug that binds heavily to proteins.
Neuropathy is a major cause of morbidity in patients with diabetes, 17,18 Numerous pharmacological treatments, both approved and unauthorized, have been used to reduce pain associated with PND and improve patients' quality of life, 53—55 These treatments include antidepressant, anticonvulsant, analgesic and topical medications. The AAN guidelines recommend the anticonvulsant drug pregabalin as a first-line treatment. Other suggested treatments include venlafaxine, duloxetine, amitriptyline, gabapentin, valproate and opioids (i.e., diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus. Strict glycemic control, focused on reducing hemoglobin A1C and increasing time within the target glucose range, together with the control of metabolic risk factors constitute the cornerstone of NPD prevention. However, there is limited evidence to support the effectiveness of glycemic and metabolic control in reducing the symptoms and complications of PND, including pain once a painful PND occurs.
Treatments for DPN include pharmacological agents and non-pharmacological interventions, such as foot care and lifestyle modifications. Pharmacological agents primarily address pain symptoms, affecting 25 to 35% of people with DPN. First-line drugs include the anticonvulsants pregabalin and gabapentin, the serotonin and norepinephrine reuptake inhibitors duloxetine and venlafaxine, and secondary amine tricyclic antidepressants, such as nortriptyline and desipramine. All drugs have unique pharmacological, clinical, and safety profiles, and drug selection should be guided by the presence of comorbidities, potential adverse effects, drug interactions, and costs.
Even with current treatment options, people are often prescribed a lower than recommended dose of medications, leading to poor management of DPN symptoms and discontinuation of treatment. By keeping up with the latest therapeutic algorithms and treatment options, healthcare professionals can improve care for people with DPN. Treatment for peripheral neuropathy may include treatment of any underlying cause or symptom. Treatment may be more successful for certain underlying causes.
For example, ensuring that diabetes is well controlled can help improve neuropathy or, at least, prevent it from worsening. The relationship between obstructive sleep apnea and intraepidermal nerve fiber density, PARP activation and foot ulceration in patients with type 2 diabetes. Effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy in patients with type 2 diabetes, in relation to the suppression of N (varepsilon) -carboxymethyl lysine. Evaluation of risk factors for diabetic foot ulceration and their impact on the prognosis of the disease.
The variability of fasting plasma glucose and the risk of painful diabetic peripheral neuropathy in patients with type 2 diabetes. Tesfaye and colleagues investigated whether the combination of duloxetine and pregabalin in patients with DPN who did not respond to either drug would be better than increasing each drug to the maximum recommended dose. Most of the evidence is in favor of capsaicin and lidocaine, although there are some publications that suggest that clonidine and isosorbide dinitrate may have some symptomatic benefit in reducing neuropathic pain in people with diabetes. In fact, people with DPN are two to three times more likely to fall than people with diabetes who don't have peripheral neuropathy.
The most common adverse effects associated with the use of gabapentin were those expected and included dizziness, somnolence, peripheral oedema and gait disturbances. The major classes of drugs used to treat diabetic peripheral neuropathic pain include tricyclic antidepressants, anticonvulsants, serotonin and noradrenaline reuptake inhibitors, opiates and opiate-like substances, and topical medications. In the peripheral nervous system, mitochondria in small and large fibers use glucose and lipids to produce adenosine triphosphatase, which supplies the energy needed for nerve impulses.
