Treatment of Neuropathic Pain with Venlafaxine: A Systematic Review.

OBJECTIVE: To investigate the efficacy of venlafaxine for neuropathic pain and review literature to determine if the medication provides adequate neuropathic pain relief. METHODS: Literature was reviewed on MEDLINE using various key words. These key words include: "venlafaxine and pain," "venlafaxine ER and pain," "venlafaxine XR and pain," "venlafaxine and neuropathic pain," "venlafaxine and neuropathy," "SSRI and neuropathic pain," "SSRI and neuropathy," "SNRI and neuropathic pain," "SNRI and neuropathy," "serotonin reuptake inhibitor and neuropathic pain," "serotonin reuptake inhibitor and neuropathy," "serotonin norepinephrine reuptake inhibitor and neuropathic pain" and "serotonin norepinephrine reuptake inhibitor and neuropathy." Using this guideline, 13 articles were reviewed. RESULTS: A total of 13 studies reviewed, which are organized by date and diagnosis. It is evident that in the majority of studies, when compared with a placebo, there was a clinical significant reduction in neuropathic pain relief when using venlafaxine. Additionally, one study showed even more significant pain relief when using higher doses of venlafaxine (at least 150 mg). However, when compared with alternative neuropathic medications, venlafaxine for the most part did not perform any better in terms of efficacy. CONCLUSION: In conclusion, venlafaxine is a safe and well-tolerated analgesic drug for the symptomatic treatment of neuropathic pain, and there is limited evidence that high-dose venlafaxine (150 mg/day) can be even more beneficial. While the present evidence is quite encouraging regarding venlafaxine's use for neuropathic pain, further research is needed to continue to expand on these findings, particularly when in consideration with other possible pharmacological agents.

Pharmacist's evolving role in the nonopioid, over-the-counter, analgesic selection process.

The pharmacist provides an integral role in pain management and treatment by focusing on the selection and evaluation of analgesic agents in a process that is patient specific, patient focused, and patient centered in a personalized care plan. Counseling patients (and the families of patients) who are using acetaminophen, aspirin, and/or nonsteroidal anti-inflammatory drugs for acute musculoskeletal pain and inflammation regarding the appropriate use of these agents is a key component of the pharmacist's overall pharmacotherapeutic role. This article reviews the importance of explaining the therapeutic and nontherapeutic effects of these agents, cautions, contraindications, dosing parameters, and the avoidance of acetaminophen/aspirin and multiple nonsteroidal anti-inflammatory drug use to patients and prescribers. The article also discusses the need to evaluate the cytochrome P450 system and the patient's pharmacotherapy and comorbid disease history to identify potential drug-mediated interactions. Evaluation of patients for comorbidities, allergies, and gastrointestinal, renal, hepatic, hematologic, and cardiovascular risks is also addressed, as are essential laboratory tests and the special needs of elderly patients.

Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery, and Therapeutic Outcome.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain associated with a variety of indications, including arthritic conditions, but their usefulness is often limited by dose-dependent adverse events (AEs), such as gastrointestinal disturbances, cardiovascular events, and renal toxicity. The risk of such effects could be reduced by the use of topical formulations, which offer the potential to deliver analgesic concentrations locally, at the site of inflammation, while minimizing systemic concentrations. The topical preparations currently approved in the United States are diclofenac sodium 1.5% topical solution (containing dimethyl sulfoxide as a penetration enhancer), diclofenac sodium gel 1%, and a diclofenac hydroxyethylpyrrolidine 1.3% patch. Each of these topical NSAIDs provide drug delivery to subcutaneous tissues for the management of pain associated with osteoarthritis or soft-tissue injuries. Furthermore, these formulations are not significantly associated with the systemic AEs associated with oral NSAIDs; the most common AEs associated with topical formulations are local skin reactions, which are usually mild and self-limiting. Other topical NSAID preparations approved in the European Union include ibuprofen creams and gels, ketoprofen gel, felbinac gel and cutaneous foam, and piroxicam gel. Meta-analyses have confirmed the efficacy and safety of these preparations. However, it is important to recognize that pharmacokinetic absorption from topical formulations can vary markedly, even between different formulations of the same drug, depending on the agent, the underlying disorder, and the site of application. It is therefore essential to consider the patient, the drug, and the drug delivery mechanism when selecting a topical NSAID preparation.

Painful boney metastases.

Up to 90% of patients with metastatic or advanced stage cancer will experience significant cancer-related pain. Approximately half or more of patients diagnosed with cancer may experience bone pain. It has been estimated that tumor metastases to the skeleton affects roughly 400,000 US citizens annually. Carcinoma from breast, lung, and prostate cancers account for approximately 80% of secondary metastatic bone disease. Bone metastases may cause devastating clinical complications associated with dramatic reductions in quality of life, mobility, and independence, as well as excruciating refractory pain. Associated complications from osseous metastases also present a substantial economic burden. Currently, there are still a significantly high number of patients suffering with unrelieved pain from osseous metastases. Treatments for painful osseous metastases may not only diminish pain but also may improve quality of life and independence/mobility, and reduce skeletal morbidity, potential pathologic fractures, spinal cord compression, and other "skeletal-related events." Treatment strategies for painful osseous metastases include the following: systemic analgesics, intrathecal analgesics, glucocorticoids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation and cryoablation), bisphosphonates, chemotherapeutic agents, inhibitors of RANKL-RANK interaction (eg, denosumab), hormonal therapies, interventional techniques (eg, kyphoplasty), and surgical approaches. Although the mechanisms underlying the development of bone metastases remain incompletely understood, there appears to be important bi-directional interactions between the tumor and the bone microenvironment. A greater understanding of the pathophysiology of painful osseous metastases may lead to better and more selective targeted analgesic therapy. Additionally, potential future therapeutic approaches to painful osseous metastases may revolutionize approaches to analgesia for this condition, leading to optimal outcomes with maximal pain relief and minimal adverse effects.

Management of auditory hallucinations as a sequela of traumatic brain injury: a case report and a relevant literature review.

A patient with progressively worsening auditory hallucinations and 30-year history of traumatic brain injury (TBI) was reported. To formulate a comprehensive diagnostic and treatment approach to patients with auditory sensory disturbances and other neuropsychiatric sequela of a TBI, an electronic search of the major behavioral science databases (PubMed, PsycINFO, Medline) and a textbook review were conducted to retrieve studies detailing the clinical characteristics, biological mechanisms, and therapeutic approaches to post-TBI psychosis. Additional references were incorporated from the bibliographies of the retrieved articles. Although infrequent, auditory hallucinations is a debilitating complication of TBI that can manifest itself 4-5 years after the occurrence of TBI. Because the age range of TBI survivors is 15-24 years, and the chance of developing post-TBI psychosis is reported to be up to 20%, this chronic neuropsychiatric complication and the available treatment options warrant close scrutiny from the clinical and the biomedical research community. Our case report and literature review demonstrates a clear need for a large, well-designed randomized trials to compare properties and efficacies of different, available, and promising pharmacotherapy agents for the treatment of post-TBI psychosis.

Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. OBJECTIVES: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. METHODS: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed. The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain. Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations. LIMITATIONS: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. CONCLUSION: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded - and herein recommended - that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments.

The management of neuropathic pain with a focus upon older adults.

By the year 2030, it is projected that the US population over the age of 65 years will be 70 million (one-fifth of the US population). Pain of various etiologies initiates about 50% of yearly physician visits and is the most frequent reason for health care consultation in the United States identified commonly by the older patient. The negative impact on the patient coupled with less than optimal treatments often presented to the patient elicit patient and prescriber frustration with inadequate outcomes. This article is focused at pharmacotherapeutic selections to be utilized in a polymodal fashion for the older adult presenting with neuropathic pain. The pharmacotherapies are to be titrated in a patient-specific patient centered-patient focused-personalized pharmacotherapeutic care. The classes of agents discussed include antidepressants, mood stabilizers/antiseizure agents, opioids, anesthetics, and miscellaneous agents.

Epidemiology of Depressive Disorders in Patients With Liver Cirrhosis: A Population-Based Study in the United States.

Objective: Major depressive disorder (MDD) is a chronic, debilitating mood disorder associated with poor medical outcomes. MDD has a multifactorial etiology with numerous biopsychosocial factors implicated as risk factors. Functional and psychiatric impairments have been evaluated in patients with liver cirrhosis; however, less is known about the prevalence and risk factors for the development of MDD in those patients. The objective of this study was to evaluate the risk of developing depression among adult patients with liver cirrhosis in the United States.Methods: Data were collected using a commercial database, an aggregate of electronic health record data from 26 major integrated US health care systems consisting of 360 hospitals in the US from 1999 to 2019.The study cohort was retrieved by searching the database for a Systematized Nomenclature of Medicine-Clinical Terms diagnosis of "cirrhosis of liver" during the designated period of the study.The following factors were adjusted for in the analyses: age, sex, race, smoking, alcohol, substance abuse, underlying mental disorders, and comorbidities.Results: 56,197,690 adults were identified between 1999 and 2019. Of those, 293,150 had a diagnosis of liver cirrhosis. The prevalence of depression among those cirrhotic patients was 23.93% versus 7.61% in the noncirrhotic control group (95% CI, 16.1836%-16.4770%; P < .0001). By applying a multivariate analysis model, cirrhotic patients were found to be more likely to develop depression (odds ratio = 2.172; 95% CI, 2.159-2.185; P < .0001) compared to patients with no prior history of liver cirrhosis.Conclusions: Liver cirrhosis is associated with increased risk of depression and is likely to be an independent risk factor in its development. Future efforts should focus on the identification and treatment of this debilitating condition in those with liver cirrhosis via an integrated care model.

Personalized pharmacotherapy for treatment approaches focused at primary insomnia.

The treatment of primary insomnia may be complex and clinically challenging. A comprehensive multidimensional evaluation with a thorough history and physical examination coupled with appropriate testing/imaging will facilitate development of a working diagnosis. Optimal treatment strategies of challenging cases typically involve interdisciplinary team approaches (including a sleep medicine specialist) providing multimodal approaches to treatment, including nonpharmacologic and pharmacologic strategies. A stepped care approach to treatment may serve as a useful guide for health care providers unfamiliar with sleep disturbance issues. Treatment plans based on sound medical judgment, clinical insight, and a thorough and global understanding of particular patient's comorbid conditions may lead to optimal patient-specific/patient-focused/patient centered personalized care.

Brain reward circuitry: The overlapping neurobiology of trauma and substance use disorders.

Mental health symptoms secondary to trauma exposure and substance use disorders (SUDs) co-occur frequently in both clinical and community samples. The possibility of a shared aetiology remains an important question in translational neuroscience. Advancements in genetics, basic science, and neuroimaging have led to an improved understanding of the neural basis of these disorders, their frequent comorbidity and high rates of relapse remain a clinical challenge. This project aimed to conduct a review of the field's current understanding regarding the neural circuitry underlying posttraumatic stress disorder and SUD. A comprehensive review was conducted of available published literature regarding the shared neurobiology of these disorders, and is summarized in detail, including evidence from both animal and clinical studies. Upon summarizing the relevant literature, this review puts forth a hypothesis related to their shared neurobiology within the context of fear processing and reward cues. It provides an overview of brain reward circuitry and its relation to the neurobiology, symptomology, and phenomenology of trauma and substance use. This review provides clinical insights and implications of the proposed theory, including the potential development of novel pharmacological and therapeutic treatments to address this shared neurobiology. Limitations and extensions of this theory are discussed to provide future directions and insights for this shared phenomena.

Fibromyalgia syndrome: a discussion of the syndrome and pharmacotherapy.

Fibromyalgia is a complex condition that is characterized by chronic widespread pain and multiple other symptoms, including fatigue, sleep disturbances, cognitive dysfunction, stiffness, and depressive episodes. Fibromyalgia may coexist and/or overlap with other conditions that may involve central sensitivity, including chronic fatigue syndrome, irritable bowel syndrome, irritable bladder syndrome or interstitial cystitis, and temporomandibular disorder. The pathophysiology of fibromyalgia remains uncertain but is believed to be partly the result of central systems affecting afferent processing as well as impaired endogenous pain-inhibitory systems. Abnormal central nociceptive processing may contribute to fibromyalgia, producing heightened responses to various noxious stimuli with resulting mechanical hyperalgesia. Fibromyalgia remains a clinical diagnosis. There has been a recent paradigm shift away from requiring 11 or more out of 18 tender points and instead focusing on the presence of chronic widespread pain as well as symptoms of fatigue, unrefreshed sleep, and other somatic complaints. Although there is no known cure for fibromyalgia, multidisciplinary team efforts using combined treatment approaches, including patient education, aerobic exercise, cognitive behavioral therapy, and pharmacologic therapies (serotonin norepinephrine reuptake inhibitors [eg, duloxetine, milnacipran] and alpha 2-delta receptor ligands [eg, pregabalin]) may improve symptoms as well as function of patients with fibromyalgia.

Effect of ethanol on the release of morphine sulfate from Oramorph SR tablets.

Recent data have shown that rapid release of active drug (i.e., dose-dumping) can occur when modified-release formulations of pain medications, and other extended-release pharmacotherapies, are exposed to ethanol in vitro. Dose-dumping of sustained-release opioids is of particular concern because of the risk for serious and potentially fatal adverse events. Sustained-release morphine sulfate tablets (Oramorph SR, 15, 30, 60, and 100 mg; Xanodyne Pharmaceuticals, Inc., Newport, KY) were incubated in vitro at simulated physiologic conditions in media containing no ethanol or ethanol in concentrations ranging from 4%-40% v/v. Morphine sulfate release was measured over the course of 1 to 24 hours using a high-performance liquid chromatography method (United States Pharmacopeia). The sustained-release morphine sulfate tablets exhibited no evidence of active drug dose-dumping. Regardless of ethanol concentration, ethanol exposure did not increase the rate of release of morphine sulfate. Release of approximately 20%-25% of the morphine sulfate dose within 1 hour was consistent among the morphine doses tested and ethanol concentrations. Release of morphine sulfate from the 60- and 100-mg tablets exposed to the higher ethanol concentrations (20% and 40% ethanol) was slightly delayed at all time points beyond 1 hour. The results of this in vitro study suggest that ethanol concentrations as high as 40% do not substantially alter the sustained-release properties of the morphine sulfate tablets.

Resuscitation and rescue of the pharmaceutical detail: a prescriber-drug representative collaboration.

The traditional pharmaceutical detail must be revised to meet current prescriber presentation and interaction needs. Best practice and evidence-based clinical strategies demands, an expanded database describing prescribable pharmaceutical therapies. We present a format for the structure of a functional database for pharmaceuticals and a means by which the data can be introduced, updated and instituted.

The pharmacist's role in the nonsteroidal anti-inflammatory drug selection process.

The pharmacist provides an integral role in pain management and treatment by focusing on the selection and evaluation of analgesic agents in a process that is patient specific and patient centered. Counseling patients (and the families of patients) who are using nonsteroidal anti-inflammatory drugs (NSAIDs) for acute musculoskeletal pain and inflammation regarding the appropriate use of these agents is a key component of the pharmacist's overall pharmacotherapeutic role. This article reviews the importance of explaining the therapeutic and nontherapeutic effects of NSAIDs and cautions, contraindications, dosing parameters, and the avoidance of multiple NSAID use to patients and prescribers. The article also discusses the need to evaluate the cytochrome P450 system and the patient's pharmacotherapy and comorbid disease history to identify potential drug interactions. Evaluation of patients for comorbidities, allergies, and gastrointestinal, renal, hepatic, hematologic, and cardiovascular risks is also addressed, as are essential laboratory tests and the special needs of elderly patients.

Extended-release Tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain.

Tramadol is a centrally acting synthetic opioid analgesic that has a dual mechanism of action, binding to mu-opioid receptors and weakly inhibiting the neuronal reuptake of norepinephrine and serotonin. Extended-release (ER) tramadol tablets (ULTRAM ER) are indicated for the management of moderate to moderately severe chronic (also referred to as persistent) pain in adults who require around-the-clock treatment of pain for an extended period of time. Because once-daily tramadol ER results in less frequent fluctuations in plasma concentrations than equivalent daily doses of short-acting tramadol, it may benefit patients experiencing pain throughout the dosing interval. On the basis of computer-generated pharmacokinetic models, one can easily transition patients who are receiving short-acting tramadol for chronic/persistent pain to tramadol ER, by calculating the current total daily dose of short-acting tramadol and starting tramadol ER at the nearest lower 100-mg-dose increment. In clinical studies, tramadol ER significantly reduced pain in patients with chronic pain from osteoarthritis and improved pain-related sleep parameters, joint stiffness, and physical function. Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications (eg, cardiovascular disease, gastrointestinal ulcer) to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors. The proven efficacy and safety profile--and the low potential for abuse--make tramadol ER a viable therapeutic option for the management of chronic/persistent nonmalignant pain in some patients. This article reviews the pharmacology, pharmacokinetics, pharmacodynamics, dosage, delivery system, administration, analgesic efficacy, and safety and tolerability profile of tramadol ER.

Chronic pain of osteoarthritis: considerations for selecting an extended-release opioid analgesic.

Chronic/persistent pain due to osteoarthritis is one of the most common pain conditions affecting Americans today. Inadequate pain relief or dissatisfaction with current treatments is a source of frustration and suffering for patients with chronic/persistent pain. The requirement of multiple doses of commonly used analgesics to maintain adequate pain relief is inconvenient for many patients with osteoarthritis-related chronic pain. The several extended-release opioid analgesics that have been developed may provide an opportunity for improved patient convenience; however, clinicians must consider adverse event profiles, pharmacokinetics, abuse potential, and controlled substance-scheduling status of extended-release opioid analgesics. The purpose of this review is to highlight the efficacy and safety of extended-release opioid analgesics utilized in the management plan of chronic pain due to osteoarthritis.

Dilemmas in chronic/persistent pain management.

The burden of chronic/persistent pain is substantial for the patient and society as a whole. Although a variety of pharmacologic treatments are available, chronic/persistent pain remains inadequately treated. Many pharmacologic treatment options provide analgesic efficacy for 4 to 6 hours, requiring multiple doses for continuous pain relief. The inconvenience of multiple doses may prevent many patients from achieving adequate pain relief. Other limitations to the current pharmacologic treatment options include gastrointestinal effects, cardiovascular effects, and organ toxicity, as well as fear of abuse or addiction. The purpose of this review is to highlight the burden of chronic/persistent pain in today's society and discuss the limitations of short-acting pharmacologic therapies used in the treatment of chronic/persistent pain.

Perspectives on the opioid crisis from pain medicine clinicians.

Patients experiencing a terminal drug related event reflect a sentinel event. If this pharmacotherapy is a widely used agent, it may be viewed as a catastrophic problem. If patients are dying from illegal drug use when the medical establishment fails them by withdrawing or minimizing their medically prescribed medication, then the burden rests with their health care providers, legislation, and insurance carriers to actively participate in a collegial fashion to achieve parity. Causing a decay in functionality in previously functional patients, may occur with appropriately prescribed opioid medications addressing non-cancer pain when withdrawing or diminishing either with or without patient consent. The members of the medical profession have diminished their prescribing of opioids for their patients out of apparent fear of reprisal, state or federal government sanctions, and other concerned groups. Diminishing former dosages or deleting the opioid medication, preferably in concert with the patient, often results in inequitable patient care. Enforcing sanctioned decreases or ceasing to prescribe from their former required/established opioid medications precipitate patient discord. In absence of opioid misuse, abuse, diversion or addiction based upon medical "guidelines" and with a poor foundation of Evidence Based Medicine the CDC guidelines, it may be masked as a true guideline reflecting a decrement of clinical judgment, wisdom, and compassion. This article also discusses the role of pharmacy chains, insurance carriers, and their pharmacy benefit managers (PBMs) contribution to this multidimensional problem. There may be a potential solution, identified in this paper, if all the associated political, medical and insurance groups work cohesively to improve patient care. This article and the CDC guidelines are not focused at hospice, palliative, end of life care pain management.

Opioid Therapy in Acute and Chronic Pain.

This is an article in the Core Entrustables in Clinical Pharmacology series that describes opioid therapy in acute and chronic pain. Opioid use during surgical procedures or anesthesia is not discussed. Basic pharmacokinetic and pharmacodynamic properties of opioids are reviewed. The safe and effective use of opioids, including clinical assessment and treatment plan, equianalgesic dosing, opioid rotation, opioid risks and side effects, and clinical adherence monitoring are discussed. Individualized opioid use can be a safe and effective component of a patient-specific multimodal treatment plan for acute or chronic pain. Adverse effects and risks can be prevented or effectively managed when anticipated and recognized. The article is followed by 4 clinical vignettes with discussions.

Pharmacotherapeutic management of pain with a focus directed at the geriatric patient.

Twenty percent to 50% of geriatric noninstitutionalized patients are victimized by pain that can result from multiple chronic medical and psychiatric diseases. This article discusses recognizing the barriers that the clinician encounters in evaluating pain in geriatric patients, taking a pain and pain medication history, and establishing a treatment plan to address the patient's experience of pain. It discusses dosage modifications appropriate for the geriatric population and reviews the drugs available to alleviate pain.