[Show abstract][Hide abstract] ABSTRACT: In Part One of this two-part series, we discussed skin physiology and anatomy as well as generalities concerning topical analgesics. This modality of therapy has lesser side effects and drug-drug interactions, and patients tolerate this form of therapy better than many oral options. Unfortunately, this modality is not used as often as it could be in chronic pain states, such as that from neuropathic pain. Part Two discusses specific therapies, local anesthetics, and other drugs, as well as how a clinician might use specific aspects of a patient's neuropathic pain presentation to help guide them in the selection of a topical agent.
[Show abstract][Hide abstract] ABSTRACT: Chronic pain is a complex disorder with multiple etiologies for which the pathologic mechanisms are still largely unknown, making effective treatment a difficult clinical task. Achieving pain relief along with improved function and quality of life is the primary goal of pain clinicians; however, most patients and healthcare professionals consider 30% pain improvement to be clinically significant-a success level that would be unacceptable in other areas of medicine. Furthermore, patients with chronic pain frequently have multiple comorbidities, including depression and sleep apnea, and most have seen several physicians prior to being seen by a pain specialist, have more than three specific pain generators, and are taking multiple medications. The addition of further oral medications to control pain increases the risk of drug-drug interactions and side effects. However, topical analgesics have the advantage of local application with limited systemic levels of drug. Topical therapies benefit from reduced side effects, lower risk of drug-drug interactions, better patient acceptability/compliance, and improved tolerability. This two-part paper is a review of topical analgesics and their potential role in the treatment of chronic pain.
[Show abstract][Hide abstract] ABSTRACT: Background:
For properly selected patients experiencing chronic pain, extended-release opioid formulations may represent an appropriate pain management choice. For the many adults, elderly, and children who have medical conditions that make swallowing solid, oral-dose formulations difficult (dysphagia) or painful (odynophagia), this option may be limited. The combination of chronic pain with dysphagia (CPD) presents a challenge to physicians and patients alike when oral opioid analgesia is needed to control pain, but patients are unable to swallow solid, oral dosage forms.
A Medline search was performed (1990 to 2013) using the search terms swallowing difficulties, dysphagia, odynophagia, adults, pediatrics, elderly, chronic pain, pain, and opioids. The following websites were searched: American Dysphagia Network, Dysphagia Research Society, World Health Organization, American Pain Society, International Association for the Study of Pain, American Academy of Pain Medicine, and American Society of Interventional Pain Physicians. Chronic pain guidelines from the following professional organizations were searched: American Pain Society, National Comprehensive Cancer Network, American Society of Interventional Pain Physicians, British Geriatric Society, European Society of Medical Oncology, World Health Organization, and the European Association for Palliative Care.
There is an unmet medical need for greater recognition of dysphagia, awareness of potential problems with medication administration in these patients, recognition of alternative drug formulations that are available for use in CPD, and an appreciation that there are new, solid, oral-dose, opioid formulations in development that can mitigate these issues associated with swallowing difficulty while still providing practical, effective analgesia. Current pharmacologic treatments have limitations; new, prospective opioid formulations in clinical development may offer physicians and patients with CPD effective treatment options while mitigating accidental exposure and abuse liability.
The number of patients with CPD may be larger than is currently anticipated by healthcare providers. Physicians should proactively include a discussion of dysphagia as part of the patient examination. CPD is an unmet medical need. There are novel opioid formulations in clinical development that address the limitations of current opioid treatments. This manuscript reviews the problems associated with dysphagia on medication administration and adherence, currently available treatment options, and opioid analgesic formulations currently in clinical development.
Current Medical Research and Opinion 09/2014; 30(12):1-71. DOI:10.1185/03007995.2014.967388 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic noncancer pain is common and consequential, affecting ∼100 million people in the United States alone and costing, when direct and indirect costs are combined, in excess of $635 billion. For certain individuals, opioids may be an effective option for the management of chronic pain; however, a series of critical decisions must be made before prescribing opioids to ensure that their potential benefits and possible risks are appropriately and realistically addressed. A thorough history, physical examination, and appropriate testing, including an assessment of risk for substance abuse, misuse, or addiction, should be conducted in patients who are being considered for opioid therapy. Proactively developing a treatment plan that matches the needs and expectations of the patient, while minimizing the potential for substance abuse, is central to the success of pain management. Current standard of care suggests that for most patients, a trial of nonopioid therapies should generally be tried first. There is no single opioid of choice that universally provides the best outcomes for all patients; thus, it is critical for the health-care practitioner to become familiar with the available subclasses, formulations, and modes of administration, and base the treatment plan on clinical experience with the drug, prior patient experience, the availability of the formulation, and cost and coverage. Pain is a dynamic phenomenon in that its characteristics and response to treatment evolve over time, as does the patient's general health state. Both positive and negative changes over time may necessitate a change in medication. Opioids can be prescribed safely and effectively, and when used with appropriate attention to individual patient characteristics may have a positive impact on pain and function. When contemplating initiation of opioid analgesics, clinicians would do well to make it clear to their patient that they will be prescribed on a trial basis with a clear exit strategy for discontinuing such treatment if there is no clear benefit including lack of analgesia, insurmountable adverse effects, and/or frank misuse or abuse of the prescribed drug.
The American Journal of Gastroenterology 09/2014; 2(1):3-8. DOI:10.1038/ajgsup.2014.3 · 10.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Available evidence to help guide efficacious nonsteroidal anti-inflammatory drug and opioid analgesic prescribing will be reviewed.
The available evidence can guide but cannot provide any prescriber with absolute knowledge regarding outcome for these frequently prescribed and potentially dangerous agents. Knowledge of the available evidence and application of such to our patients on an individualized basis hopefully will help to optimize therapeutic goals and minimize harms.
[Show abstract][Hide abstract] ABSTRACT: Background:
Non-steroidal anti-inflammatory drugs are prescribed for the treatment of patients with acute pain but use of such analgesics is associated with dose-dependent adverse events (AEs). Diclofenac submicron particle capsules have been developed using SoluMatrix technology to provide analgesia at lower doses than available solid oral dosing forms. Our study evaluated the analgesic efficacy and safety of lower-dose diclofenac submicron particle capsules in patients with acute pain following elective surgery.
A phase 3, multicenter, double-blind study enrolled 428 patients, aged 18 to 65 years, with moderate-to-severe pain following bunionectomy under regional anesthesia. Patients experiencing a pain intensity rating of ≥ 40 mm on a 100-mm Visual Analog Scale were randomized to receive lower-dose diclofenac submicron particle capsules (35 or 18 mg, 3 times daily [TID]), celecoxib (200 mg, twice daily [BID], 400-mg loading dose), or placebo. The primary efficacy parameter was the overall (summed) pain intensity difference measured over 0 to 48 hours (SPID-48). Secondary efficacy parameters included pain intensity difference (PID) at scheduled assessments.
Lower-dose diclofenac submicron particle capsules 35 mg TID (524.05; P < 0.001), 18 mg TID (393.25; P = 0.010), and celecoxib 200 mg BID (390.22; P = 0.011) demonstrated significant pain control compared with placebo (77.10) for the primary efficacy parameter, mean SPID-48. Diclofenac submicron particle capsules 35 mg TID (4.52) provided some pain control (higher mean PID) at 30 minutes following administration, in contrast to celecoxib 200 mg BID (0.80), diclofenac submicron particle capsules 18 mg TID (0.31), and placebo (0.12). Better pain control (PID) was noted across all active treatment groups at 5 hours compared with placebo (P ≤ 0.03), and pain relief was sustained throughout the treatment period. The most frequent non-procedure-related AEs were nausea, headache, dizziness, and vomiting.
Lower-dose diclofenac submicron particle capsules provided effective analgesia in this phase 3 clinical study in patients with acute pain and are a potentially promising option for the treatment of patients with acute pain.
Postgraduate Medicine 09/2013; 125(5):130-138. DOI:10.3810/pgm.2013.09.2693 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The recent increase in opioid consumption in the modern world prompted pain physicians to find new and improved solutions to tackle chronic, refractory pain syndromes. Topical analgesics are emerging as a valued multimodal analgesic arm in the fight against chronic pain.
New and improved topical formulations have emerged as effective tools to treat chronic refractory pain. In addition to formulations manufactured by the pharmaceutical industry, there has been a recent interest in mixed topical products by local, regional and national compounding pharmacies. This review will focus on advances in topical analgesics, especially their role as an effective analgesic in nociceptive and neuropathic refractory pain states. We will explore topical analgesics' mechanisms of action and their efficacy as opioid-sparing formulations.
This review will allow physicians to understand the role of topical agents in the treatment of intractable pain syndromes. Increasing medical providers' familiarity with these agents will allow their incorporation as part of a complex analgesic regimen for an improved pain management plan benefiting the patient population at large.
Current opinion in anaesthesiology 08/2013; 26(5). DOI:10.1097/01.aco.0000432514.00446.22 · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute postoperative pain remains a major problem, with both undertreatment and overtreatment leading to serious consequences, including increased risk of persistent postoperative pain, impaired rehabilitation, increased length of stay and/or hospital readmission, and adverse events related to excessive analgesic use, such as oversedation. New analgesic medications and techniques have been introduced that target the preoperative, intraoperative, and postoperative periods to better manage acute postoperative pain, with improvements in analgesic efficacy and safety over more traditional pain management approaches. This review provides an overview of these new analgesic medications and techniques. Specific topics that are discussed include the use of preoperative nonsteroidal anti-inflammatory drugs, anxiolytics, and anticonvulsants; intraoperative approaches such as neuraxial analgesia, continuous local anesthetic wound infusion, transversus abdominis plane block, extended-release epidural morphine, intravenous acetaminophen, and intravenous ketamine; and postoperative use of intravenous ibuprofen, new opioids (eg, tapentadol) or opioid formulations (morphine-oxycodone), and patient-controlled analgesia.
New, targeted, analgesic medications and techniques may provide a safer and more effective approach to the management of acute postoperative pain than traditional approaches such as postoperative oral analgesics.
Pain Practice 08/2013; 14(5). DOI:10.1111/papr.12108 · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This article aims to help primary care physicians negotiate gaps in current guidelines for postherpetic neuralgia (PHN). The objectives of this article are to: 1) briefly review the available guidelines and identify their strengths and weaknesses; 2) review the gaps in the guidelines; 3) review new data that were not included in the most recent guidelines; 4) provide expert opinion on how the new data and current guidelines can be used to make treatment decisions; and 5) review several important dimensions of care (eg, tolerability, dosing) and provide guidance. In general, all guidelines recognize the α2δ ligands, tricyclic antidepressants (TCAs), opioids, and tramadol as efficacious systemic options, with topical lidocaine serving as an efficacious nonsystemic approach for localized PHN treatment. The first-line treatment options typically recommended in the guidelines are α2δ ligands and TCAs, while opioids and tramadol are often recommended as second- or third-line options. Since the latest guidelines were published, newer agents (eg, topical capsaicin [8%] patch and gastroretentive gabapentin) have met the standard as first-line therapy with the publication of ≥ 1 randomized controlled trial. However, gabapentin enacarbil has not met this standard due to a lack of a published randomized controlled trial in PHN.
Postgraduate Medicine 07/2013; 125(4):191-202. DOI:10.3810/pgm.2013.07.2690 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tamper-resistant formulations (TRFs) of oral opioid drugs are intended to prevent certain types of abuse (eg, intranasal, intravenous). Patients raising objections to receiving a TRF may have valid concerns or may be seeking a formulation that can be more easily misused.
US clinicians experienced in pain management met in October 2011 to discuss common patient objections to being switched from a non-TRF opioid to a TRF of the same opioid. Retail pharmacy, health insurance, and scientific data were used to assess the potential validity of these patient objections.
Clinical experience switching patients from a non-TRF to a TRF opioid was limited to oxycodone controlled release (CR), as it was the only TRF available at that time; knowledge of other TRFs was limited to the scientific literature. Common objections from patients included "costs more," "not covered by insurance," "can't feel it working," and "causes adverse events." Objective retail pharmacy and insurance coverage information for oxycodone CR was accessible and indicated that patient objections were based on cost and coverage varied by insurer. Unpublished trial results (ClinicalTrials.gov) revealed that TRF oxycodone CR has a slower initial release than the non-TRF formulation, which may reduce positive subjective effects. The complaint "I can't feel it working" may reflect lessened positive subjective effects rather than reduced analgesic efficacy. Most tolerability complaints lacked objective support.
The general process used to assess the validity of patient objections to TRF oxycodone CR may be applied to other TRFs once they become available. Publication of clinical data on TRFs would help clinicians to appropriately weigh patient concerns.
Journal of Pain Research 05/2013; 6(4):367-73. DOI:10.2147/JPR.S37343
[Show abstract][Hide abstract] ABSTRACT: Editors' Note: Dr. Mauskop reviews the literature on the use of butterbur extract for migraine prophylaxis and concludes that it has the potential for serious toxicity. Authors Holland et al. disagree with Dr. Mauskop's interpretation. Dr. Sethi, in response to Drs. Stone and Edwards' "Trick or treat? Showing patients with functional (psychogenic) motor symptoms their physical signs," airs the difficulty, which most neurologists can relate to, of discussing a psychogenic diagnosis with a patient. Dr. Tfelt-Hansen calls attention to an error in the classification of evidence in the American Academy of Neurology guideline on episodic migraine prevention by Silberstein et al. The authors concur and an erratum appears in this issue. Megan Alcauskas, MD, and Robert C. Griggs, MD.
[Show abstract][Hide abstract] ABSTRACT: Oral analgesics are commonly prescribed for the treatment of acute and chronic pain, but these agents often produce adverse systemic effects, which sometimes are severe. Topical analgesics offer the potential to provide the same analgesic relief provided by oral analgesics but with minimal adverse systemic effects. This article describes the results of a systematic review of the efficacy of topical analgesics in the management of acute and chronic pain conditions. A literature search of MEDLINE/PubMed was conducted using the keywords topical analgesic AND chronic pain OR acute pain OR neuropathic pain and focused only on individual clinical trials published in English-language journals. The search identified 92 articles, of which 65 were eligible for inclusion in the review. The most commonly studied topical analgesics were nonsteroidal anti-inflammatory drugs (n=27), followed by lidocaine (n=9), capsaicin (n=6), amitriptyline (n=5), glyceryl trinitrate (n=3), opioids (n=2), menthol (n=2), pimecrolimus (n=2), and phenytoin (n=2). The most common indications were acute soft tissue injuries (n=18), followed by neuropathic pain (n=17), experimental pain (n=6), osteoarthritis and other chronic joint-related conditions (n=5), skin or leg ulcers (n=5), and chronic knee pain (n=2). Strong evidence was identified for the use of topical diclofenac and topical ibuprofen in the treatment of acute soft tissue injuries or chronic joint-related conditions, such as osteoarthritis. Evidence also supports the use of topical lidocaine in the treatment of postherpetic neuralgia and diabetic neuropathy. Currently, limited evidence is available to support the use of other topical analgesics in acute and chronic pain.
Mayo Clinic Proceedings 02/2013; 88(2):195-205. DOI:10.1016/j.mayocp.2012.11.015 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Gabapentin immediate-release formulations (G-IR) administered three times a day is an efficacious treatment for postherpetic neuralgia (PHN), but its potential benefits may not be fully realized due to tolerability issues as well as its pharmacokinetic (PK) properties such as its short half-life, and regional and saturable absorption in the proximal small intestine. The gastroretentive once-daily formulation of gabapentin (G-GR) allows for less frequent dosing while maintaining efficacy and may also reduce adverse events (AEs) associated with high plasma concentration of gabapentin occurring during the waking hours. G-GR slowly releases the drug from the tablet to the upper small intestine, where gabapentin is best absorbed, over approximately 10 h.
This report reviews the development of the gastroretentive technology used in the once-daily formulation of gabapentin (G-GR), and describes the clinical development of G-GR from PK studies through the Phase III efficacy and safety studies, with comparisons made with G-IR.
The technology takes advantage of the normal physiology of the stomach in the fed state to provide gastroretention, which in turn allows for gradual release of the active ingredient over several hours to the small intestine where gabapentin is best absorbed. The GR technology used in G-GR resulted in a decreased dosing frequency from three times per day for the IR product to once daily in the treatment of PHN, while maintaining the same efficacy with an apparent reduced incidence of AEs common to G-IR therapy.
Expert Opinion on Drug Delivery 07/2012; 9(9):1147-60. DOI:10.1517/17425247.2012.709231 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several prominent guidelines recommend that patients on long-term opioid therapy have periodic urine drug monitoring (UDM) for appropriate use; however, none address the specific questions of which patients to test, which substances to test for, how often to test, and how to act on the results.
In the absence of adequate scientific evidence in the literature, a panel of experts in the field of pain and addiction medicine was convened to develop consensus UDM recommendations. The panel met three times between March 2010 and April 2011, and reviewed several drafts of the recommendations document between meetings.
The group was able to achieve consensus on a set of UDM recommendations addressing test selection, test frequency, interpretation of results, and how to handle discrepancies based on specific results.
While the participating panel members recognize that there currently is a limited evidence base to support the expert panel's recommendations, primary care providers and pain specialists are largely acting today based on anecdote, intuition, and individual experience. The recommendations are meant to begin to provide a framework for standardizing practices for UDM in the treatment of chronic pain, and to serve as a catalyst to advance research that quantifies the effects of UDM on opioid therapy management and patient outcomes.
Pain Medicine 06/2012; 13(7):886-96. DOI:10.1111/j.1526-4637.2012.01414.x · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To provide updated evidence-based recommendations for the preventive treatment of migraine headache. The clinical question addressed was: What pharmacologic therapies are proven effective for migraine prevention?
The authors analyzed published studies from June 1999 to May 2009 using a structured review process to classify the evidence relative to the efficacy of various medications available in the United States for migraine prevention.
The author panel reviewed 284 abstracts, which ultimately yielded 29 Class I or Class II articles that are reviewed herein. Divalproex sodium, sodium valproate, topiramate, metoprolol, propranolol, and timolol are effective for migraine prevention and should be offered to patients with migraine to reduce migraine attack frequency and severity (Level A). Frovatriptan is effective for prevention of menstrual migraine (Level A). Lamotrigine is ineffective for migraine prevention (Level A).
[Show abstract][Hide abstract] ABSTRACT: To provide updated evidence-based recommendations for the preventive treatment of migraine headache. The clinical question addressed was: Are nonsteroidal anti-inflammatory drugs (NSAIDs) or other complementary treatments effective for migraine prevention?
The authors analyzed published studies from June 1999 to May 2009 using a structured review process to classify the evidence relative to the efficacy of various medications for migraine prevention.
The author panel reviewed 284 abstracts, which ultimately yielded 49 Class I or Class II articles on migraine prevention; of these 49, 15 were classified as involving nontraditional therapies, NSAIDs, and other complementary therapies that are reviewed herein.
Petasites (butterbur) is effective for migraine prevention and should be offered to patients with migraine to reduce the frequency and severity of migraine attacks (Level A). Fenoprofen, ibuprofen, ketoprofen, naproxen, naproxen sodium, MIG-99 (feverfew), magnesium, riboflavin, and subcutaneous histamine are probably effective for migraine prevention (Level B). Treatments considered possibly effective are cyproheptadine, Co-Q10, estrogen, mefenamic acid, and flurbiprofen (Level C). Data are conflicting or inadequate to support or refute use of aspirin, indomethacin, omega-3, or hyperbaric oxygen for migraine prevention. Montelukast is established as probably ineffective for migraine prevention (Level B).