Combination Therapy for Neuropathic Pain

Abstract

Neuropathic pain is a debilitating chronic condition that remains very difficult to treat. Recently, a number of clinical studies have compared the effectiveness of combination drug therapy with monotherapy for neuropathic pain treatment. In this article, we summarize up-to-date clinical studies of combination therapy for the treatment of both cancer- and non-cancer-related neuropathic pain. Despite a relatively small number of clinical studies on this topic, several positive indications have emerged. First, clinical studies using gabapentin (five positive trials) and pregabalin (five positive trials and one negative trial) in combination with an opioid, cyclo-oxygenase-2 inhibitor or antidepressant have shown positive responses greater than the respective monotherapies for pain related to diabetic neuropathy and postherpetic neuropathy. Second, high-concentration (8%) topical capsaicin and a 5% lidocaine patch seem to be effective add-on therapies (a modality of combination therapy) for various neuropathic pain conditions. Third, combination therapy for cancer-related neuropathic pain has yielded only limited success based on a number of small-scale clinical studies. While there are benefits of using combination therapy for neuropathic pain treatment, including better pain relief and reduced adverse effects, more clinical studies are required in order to (i) make head-to-head comparisons between combination and single-drug therapies, (ii) identify symptom-specific combination therapies for distinctive clinical neuropathic pain conditions, (iii) explore combination therapies that include non-drug modalities such as physical therapy, psychological coping and biofeedback to facilitate functional restoration and (iv) develop new and objective evaluation tools for clinical outcome assessment.

Transdermal Buprenorphine Relieves Neuropathic Pain: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial in Diabetic Peripheral Neuropathic Pain

“…The management of DPNP is challenging, and although opioids are not a first-line therapy, they are commonly used with adjuvants to manage neuropathic pain (21,22). To our knowledge, this is the first high-quality, randomized, double-blind, placebo-controlled trial to assess the effectiveness of buprenorphine patches for the symptomatic relief of DPNP.…”

Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation

“…1 Several studies have suggested a potential analgesic activity of antidepressants independent of their effects on mood. [2][3][4][5][6] Furthermore, it has been reported that heterocyclic antidepressants are able to modulate the immune system. [7][8][9] In addition, a clear reciprocal effect between inflammatory mediators and development of depression is even more evident.…”

Recent and Emerging Trends in Pharmacotherapy of Neuropathic Pain

“…In a RCT on patients with neuropathic pain with prominent allodynia, at doses of up to 900 mg/d, mexiletine showed no significant effects on pain and allodynia of NP. [54,55,56] Combination therapy Neuropathic pain is a complex syndrome and most of the monotherapies often fail to provide sufficient analgesia even at the highest recommended dose [57] because a single drug is unable to effectively modify the complex cellular and molecular changes seen in chronic NP conditions. [58] Therefore, it is logical to target different pain mechanisms using combination therapy.…”

“…Although combining opioid analgesic as a part of combination therapy provided better pain control in the majority studies but more clinical studies are needed for long time follow up of patients to fully evaluate the risk and long-term adverse effects . [57] Both short and long-term safety studies are required to evaluate possible adverse effects resulting from the combinations therapies used for NP.…”