Pharmacokinetics of immediate release, extended release, and gastric retentive gabapentin formulations in healthy adults
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OBJECTIVE: Gabapentin immediate release (GBP-IR), gabapentin gastric retentive (GBP-GR), and the prodrug gabapentin enacarbil extended release formulation (GEn) have been approved for management of postherpetic neuralgia (PHN) in adults. This is the first pharmacokinetic (PK) comparison of all three formulations using FDA-recommended doses for PHN. MATERIALS: This study compared the steady-state PK of GBP-IR 600 mg t.i.d., GBP-GR 1,800 mg q.d., and GEn 600 mg b.i.d. in healthy adults. METHODS: The open-label study consisted of a 3-day lead-in of escalating doses of GBP-IR, 5 days of treatment with each formulation (GPB-IR, GPB-GR, and GEn), and a 7-day taper period on 600 mg GEn q.d.. Plasma concentrations were collected on day 5 for each formulation. PK parameters were estimated from plasma concentration data. RESULTS: 14 healthy subjects (7 men, 7 women; mean (SD) age, 46.8 (7.60) years; mean (SD) body mass index, 26.7 (1.7) kg/m2) received all doses and completed the study. GBP-GR resulted in substantially (~ 4-fold) higher peak-to-trough ratio and percent fluctuation compared to GEn. GEn resulted in more sustained and less fluctuating daily exposure relative to GBP-IR, particularly at the end of 24 hours of dosing. In contrast, gabapentin fluctuation from GBP-IR consisted of 3 distinct peaks. After dose normalization, gabapentin exposure with GEn was ~ 2.2-fold and ~ 1.4-fold higher compared to GBP-GR and GBP-IR, respectively. All treatments were well tolerated. CONCLUSION: GEn requires less frequent dosing compared with GBP-IR and fluctuates less with sustained gabapentin exposure throughout the day. These PK differences may have clinically relevant implications.
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Recommendations for urine drug monitoring as a component of opioid therapy in the treatment of chronic pain.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Evaluating malingering in contested injury or illness.

An interdisciplinary task force of physicians and neuropsychologists with advanced training in impairment and disability assessment provided a review of the literature on malingering in chronic pain, medical disorders, and mental/cognitive disorders. Our review suggests that treating health care providers often do not consider malingering, even in cases of delayed recovery involving work injuries or other personal injuries, where there may be a significant incentive to feign or embellish symptoms or delay recovery. This report discusses the implications of this issue and offers recommendations to evaluating physicians and other health care professionals.

What Do We Know About the Pathophysiology of Chronic Pain? Implications for Treatment Considerations.

We discuss the complex features of the pathophysiology of chronic pain and the implications for treatment and provide an overview of nociceptive processes, neuropathic pain, cold hyperalgesia, peripheral nerve injury, wind-up pain, central sensitization, and common clinical presentation and diagnostic criteria. Advanced medicine has proven that chronic pain need not involve any structural pathology as pain is a complex biopsychosocial experience. Treatment of the specific mechanisms responsible for pain should be aimed at preventing and or reducing dysfunctional neuro-plasticity resulting from poorly controlled chronic pain. Further study is needed to reduce the probability and of persistent changes that cause chronic pain.

The prediction of treatment outcome at a multidisciplinary pain center.

The purpose of this study was to determine if some commonly used admission variables could predict treatment outcome on a multidisciplinary pain center. Specifically, it was designed as a prospective study of an index proposed by Maruta et al. The subjects were 104 patients. The 4 outcome measures used were staff judgment, patient judgment, change in pain scores and change in mood. With the exception of a negative correlation with age, none of the other variables predicted outcome. The index of Maruta did not predict outcome.

A review of follow-up studies of multidisciplinary pain units.

Chronic pain is a major public health problem in the United States. Estimates from the National Institutes of Health put the cost of chronic pain at 40 billion dollars a year. They estimate that as many as 15 million adults suffer from low back pain with a minimum cost of 5 billion dollars in direct medical costs and 93 million work days lost every year. In an attempt to cope with this massive problem, multidisciplinary pain units have arisen which attempt to address the complex, multi-faceted aspects of a chronic pain problem. The importance of this new treatment approach is made evident by the 1981 overview of multidisciplinary pain centers published by the National Institutes of Health. In this publication, the history and success of these units since their first development by Bonica are evidenced. The purpose of the present paper is to briefly, critically summarize one small aspect of these programs, specifically follow-up analysis of the patients after discharge.

Evidence-based oral transmucosal fentanyl citrate (OTFC) dosing guidelines.

OBJECTIVE: To review the evidence for dosing and efficacy of oral transmucosal fentanyl citrate in the management of pain and produce dosing guidelines. DESIGN: The scientific literature pertaining to oral transmucosal fentanyl citrate was reviewed, focusing upon its pharmacology and clinical experience with use in cancer and noncancer pain. Emphasis was upon published, peer-reviewed English language articles. RESULTS: Information was crucially examined and synthesized into guidelines for use and dosing of oral transmucosal fentanyl citrate in cancer and noncancer pain. CONCLUSIONS: Oral transmucosal fentanyl citrate is a potent opioid delivery system, which, when used appropriately, is an effective treatment option for pain. Adherence to guidelines should promote its safe and efficacious use in a variety of clinical pain management settings.

Pain: psychiatric aspects of impairment and disability.

Patients with chronic pain frequently experience a complex and convoluted journey through the health care system that often is unrewarding for all involved. As job satisfaction and financial security diminish during our economic recession, the impact of the disability epidemic becomes more profound. There often is no direct correlation between objective impairment and a patient's request for disability status. Injured workers maintained on workers' compensation may have an increased risk for developing chronic pain syndromes unresponsive to conventional treatments. These patients may have significant financial, psychosocial, and environmental reinforcement for maintenance of their disability and little incentive to return to work. Excessive pain behavior may lead to unnecessary diagnostic testing or invasive procedures and result in iatrogenic complications and prolonged disability. Patients with chronic pain syndrome who have not had psychosocial treatment may not be at maximum medical improvement. The purpose of this paper is to help the readership identify types of psychiatric, psychologic, and psychosocial issues that can coexist in patients with chronic pain who are applying for disability, and to help treating physicians avoid contributing to iatrogenic pain and disability by performing needless and potentially harmful procedures on patients who may be better served with an emphasis on psychiatric or psychologic care.

American Academy of Disability Evaluating Physicians (AADEP) position paper: complex regional pain syndrome I (RSD): impairment and disability issues.

OBJECTIVE: To provide an overview and methodology for the evaluation of impairment and functional residual capacity in complex regional pain syndrome I (CRPS I, RSD). This paper is intended to provide assistance to physicians asked to evaluate impairment- and disability-related issues and is not primarily geared to guide treatment of the CRPS I patient. METHOD: Conference and literature review by neurology, anesthesiology, pain medicine, physiatry, and disability evaluating physicians followed by description of issues, options, and recommendations based upon the committee's deliberations and the widely used AMA Guides to the Evaluation of Permanent Impairment, fourth and fifth editions. The authors present functional criteria for assessing the severity of CRPS. These criteria were developed by committee consensus opinion based on multidisciplinary clinical experience considering daily functional issues. They can be used in conjunction with CRPS-ADL Classes of Impairment in order to categorize an individual into a specific class for purposes of permanent impairment rating. Future reliability and validity studies of this rating scale are pending future use, acceptance and, hopefully, additional studies. RESULTS: Evaluators should perform a comprehensive assessment of patients with CRPS I to make an accurate diagnosis and exclude other conditions that could explain the symptoms and signs of the condition. While radiological, laboratory, and other diagnostic studies may be of assistance in making the diagnosis, in the final analysis, this is a clinical diagnosis. Impairment is based on objectively validated limitation in activities of daily living (ADL).