Comparative effectiveness of pain control between opioids and gabapentinoids in older patients with chronic pain.

ABSTRACT: Gabapentinoid (GABA) prescribing has substantially increased while opioid prescribing has decreased since the 2016 Centers for Disease Control and Prevention Guidelines restricted opioid prescribing for chronic pain. The shift to GABA assumes equal analgesic effectiveness to opioids, but no comparative analgesic effectiveness data exist to support this assumption. We compared GABA to opioids by assessing changes in pain interfering with activities (activity-limiting pain) over time in patients with chronic pain. We used 2017 to 2019 data from a 20% national sample of Medicare beneficiaries diagnosed with chronic pain who initiated a GABA or opioid prescription for ≥30 continuous days and received home health care in the study year. The main outcome was the difference in reduction in pain score from pre- to post-prescription assessments between the 2 groups. Within a 60-day window before-and-after drug initiation, our sample comprised 3208 GABA users and 2846 opioid users. Reduction in post-prescription scores of pain-related interference with activities to less-than-daily pain was 48.1% in the GABA group and 41.7% in the opioid group; this remained significant (odds ratio = 1.29, 95% confidence interval: 1.17-1.43, P < 0.0001) after adjustment for patient demographics and comorbidities. The adjusted difference in reduced pain-related interference score between the 2 groups was -0.10 points on a 0 to 4 scale ( P = 0.01). Gabapentinoid use had greater odds of less-than-daily pain post-prescription, in a dose-dependent manner. Thus, GABA use was associated with a larger reduction in chronic pain than opioids, with a larger effect at higher GABA dosage. Future research is needed on functional outcomes in patients with chronic pain prescribed GABA or opioids.

Tricyclic Antidepressant and/or γ-Aminobutyric Acid-Analog Use Is Associated With Fall Risk in Diabetic Peripheral Neuropathy.

BACKGROUND/OBJECTIVES: Peripheral neuropathy is a common diabetes complication that can increase fall risk. Regarding fall risk, the impact of pain management using tricyclic antidepressants (TCAs) or γ-aminobutyric acid (GABA) analogs is unclear because these medications can also cause falls. This study investigates the impact of these drugs on fall and fracture risk in older diabetic peripheral neuropathy (DPN) patients. DESIGN: Historical cohort study with 1-to-1 propensity matching of TCA/GABA-analog users and nonusers. SETTING: Nationally representative 5% Medicare sample between the years 2008 and 2010. PARTICIPANTS: After applying all selection criteria, 5,550 patients with prescription and 22,200 patients without prescription of TCAs/GABA-analogs were identified. Both patient groups were then stratified for fall history and matched based on propensity of receiving TCAs/GABA-analogs within each group. MEASUREMENTS: Patients were followed until the first incidence of fall or the first incidence of fracture during the follow-up period (for up to 5 years). RESULTS: After matching, users and nonusers were largely similar. After covariate adjustment, TCA/GABA-analog use was associated with a statistically significant increase in fall risk (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 1.03-1.20), but was not associated with fracture risk (adjusted HR = 1.09; 95% CI = 0.99-1.19) in the conventional analysis. Treating TCA/GABA-analog use as a time-dependent covariate resulted in statistically significant associations of TCA/GABA-analog use with both fall and fracture risk (HR = 1.26 [95% CI = 1.17-1.36]; and HR = 1.12 [95% CI = 1.02-1.24], respectively). CONCLUSION: Among older patients with DPN, GABA-analogs or TCAs increase fall risk and possibly fracture risk. Use of these medications is therefore a potentially modifiable risk factor for falls and fractures in this population.

Clinical and economic consequences of treating patients with peripheral neuropathic pain with brand name or generic drugs in routine clinical practice: The effects of age and sex. / Efecto de la edad y el género sobre las consecuencias clínicas y económicas del tratamiento con especialidad farmacéutica de marca o genérica en pacientes con dolor neuropático periférico en práctica clínica habitual.

OBJECTIVE: We aimed to analyse the effects of age and sex on pain and cost for patients with chronic peripheral neuropathic pain (PNP) who have started treatment with brand name gabapentin versus generic gabapentin (EFG). METHODS: We conducted a retrospective multicentre study using electronic medical records (EMR) for patients of both sexes, older than 18, who began treatment with brand name or generic gabapentin. Adherence (medication possession ratio [MPR]), persistence, use of healthcare resources, cost, and pain reduction were measured for one year. RESULTS: We analysed 1369 EMRs [61.1% women; mean age 64.6 (15.9), 52.4%≥65 years]; 400 used brand name drugs while 969 used generic gabapentin. Persistence and adherence were higher in patients using brand name gabapentin (7.3 vs 6.3 months, P<.001; 86.5% vs 81.3% MPR, P<.001). Lower healthcare costs were observed in patients using brand-name gabapentin in both age groups (<65 and ≥65). Mean difference in cost per patient amounted to €221 (95%CI: 59-382) and €217 (95%CI: 51-382) in the <65 and ≥65 age groups, respectively (P<.01). Mean difference in cost among men amounted to €197 (63-328), while mean difference in cost among women amounted to €239 (96-397) (P=.005 and P=.004, respectively). Compared with EFG, brand treatment showed greater pain relief: 13.5% (10.9-16.2) and 10.8% (8.2-13.5) in <65 and ≥65year patients, respectively (P<.001), and 10.7% (8.2-13.2) and 13.8% (11.0-16.5) in women and men respectively (P<.001). CONCLUSIONS: Regardless of sex and age, patients who started PNP treatment with brand name medication showed greater persistence and adherence to treatment than those taking generic drugs. Brand name treatment also involved lower healthcare costs, and greater pain relief.

Cost of treatment of peripheral neuropathic pain with pregabalin or gabapentin in routine clinical practice: impact of their loss of exclusivity.

To analyze the effect of loss of exclusivity of data on the cost of treatment of peripheral neuropathic pain (PNP) with pregabalin or gabapentin in routine clinical practice. A retrospective observational study, with electronic medical records for patients enrolled at primary care centers managed by the health care provider Badalona Serveis Assistencials, who initiated treatment of PNP with pregabalin or gabapentin. The analysis used drugs and resources prices for year 2015. The 1163 electronic medical records (pregabalin; N = 764, gabapentin; N = 399) for patients (62.2% women) with a mean (standard deviation) age of 59.2 (14.7) years were analyzed. Treatment duration was slightly shorter with pregabalin than with gabapentin (5.2 vs 5.5 months; P = 0.124), with mean doses of 227.4 (178.6) mg and 900.0 (443.4) mg, respectively. The average study drug cost per patient was higher for pregabalin than for gabapentin; €214.6 (206.3) vs €157.4 (181.9), P < 0.001, although the cost of concomitant analgesic medication was lower; €176.5 (271.8) vs €306.7 (529.2), P < 0.001. The adjusted average total cost per patient was lower in those treated with pregabalin than in those treated with gabapentin; €2,413 (2119-2708) vs €3201 (2806-3.597); P = 0.002, owing to significantly lower health care costs; €1307 (1247-1367) vs €1538 (1458-1618), P < 0.001, and also non-health care costs; €1106 (819-1393) vs €1663 (1279-2048), P = 0.023, that was caused by a significantly lower use of concomitant medication, fewer medical visits to primary care, and fewer days of sick leave. After loss of exclusivity of both drugs, pregabalin continued to show lower health care and non-health care costs than gabapentin in the treatment of PNP in routine clinical practice.

Gabapentin for the Management of Chronic Pelvic Pain in Women (GaPP1): A Pilot Randomised Controlled Trial.

Chronic pelvic pain (CPP) affects 2.1-24% of women. Frequently, no underlying pathology is identified, and the pain is difficult to manage. Gabapentin is prescribed for CPP despite no robust evidence of efficacy. We performed a pilot trial in two UK centres to inform the planning of a future multicentre RCT to evaluate gabapentin in CPP management. Our primary objective was to determine levels of participant recruitment and retention. Secondary objectives included estimating potential effectiveness, acceptability to participants of trial methodology, and cost-effectiveness of gabapentin. Women with CPP and no obvious pelvic pathology were assigned to an increasing regimen of gabapentin (300-2700 mg daily) or placebo. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to six months. The analyses by treatment group were by intention-to-treat. Interviews were conducted to evaluate women's experiences of the trial. A probabilistic decision analytical model was used to estimate cost-effectiveness. Between September 2012-2013, 47 women (34% of those eligible) were randomised (22 to gabapentin, 25 to placebo), and 25 (53%) completed six-month follow-up. Participants on gabapentin had less pain (BPI difference 1.72 points, 95% CI:0.07-3.36), and an improvement in mood (HADS difference 4.35 points, 95% CI:1.97-6.73) at six months than those allocated placebo. The majority of participants described their trial experience favorably. At the UK threshold for willingness-to-pay, the probabilities of gabapentin or no treatment being cost-effective are similar. A pilot trial assessing gabapentin for CPP was feasible, but uncertainty remains, highlighting the need for a large definitive trial.

Impact of Data Imputation Methodology on Pain Assessment over 24 Hours in a Randomized, Placebo-Controlled Study of Gabapentin Enacarbil in Patients with Neuropathic Pain Associated with Postherpetic Neuralgia.

OBJECTIVE: To assess the impact of gabapentin enacarbil on primary and secondary pain endpoints using three data imputation methodologies in a randomized phase II study of adult patients with postherpetic neuralgia. METHODS: The primary endpoint was change from baseline to end of maintenance treatment in mean 24-hour average pain intensity score. Secondary endpoints (daytime/nighttime average pain intensity score, daytime/nighttime current pain intensity score, and daytime/nighttime worst pain intensity score) were based on daily electronic diary assessments. Comparisons of each gabapentin enacarbil dose with placebo were performed using three different statistical methodologies: last observation carried forward, baseline observation carried forward, and mixed-effect model for repeated measures. RESULTS: Of the 376 randomized patients, 371 were in the intent-to-treat population (gabapentin enacarbil 1,200 mg, 107; 2,400 mg, 82; 3,600 mg, 87; placebo, 95). For mean 24-hour average pain intensity score, there were statistically significant improvements from baseline to end of maintenance treatment for all gabapentin enacarbil groups vs placebo using the three analysis methods. Significant improvements were also observed for all secondary endpoints with gabapentin enacarbil 1,200 mg using the three analysis methods. Most secondary endpoints also showed improvements following treatment with gabapentin enacarbil 2,400 mg or 3,600 mg compared with placebo. CONCLUSIONS: Gabapentin enacarbil (1,200 mg, 2,400 mg, and 3,600 mg) was effective and well tolerated in patients with postherpetic neuralgia compared with placebo, as confirmed by three different and robust statistical methodologies.

Long-term cost-effectiveness of initiating treatment for painful diabetic neuropathy with pregabalin, duloxetine, gabapentin, or desipramine.

Painful diabetic neuropathy (PDN) affects nearly half of patients with diabetes. The objective of this study was to compare the cost-effectiveness of starting patients with PDN on pregabalin (PRE), duloxetine (DUL), gabapentin (GABA), or desipramine (DES) over a 10-year time horizon from the perspective of third-party payers in the United States. A Markov model was used to compare the costs (2013 $US) and effectiveness (quality-adjusted life-years [QALYs]) of first-line PDN treatments in 10,000 patients using microsimulation. Costs and QALYs were discounted at 3% annually. Probabilities and utilities were derived from the published literature. Costs were average wholesale price for drugs and national estimates for office visits and hospitalizations. One-way and probabilistic (PSA) sensitivity analyses were used to examine parameter uncertainty. Starting with PRE was dominated by DUL as DUL cost less and was more effective. Starting with GABA was extendedly dominated by a combination of DES and DUL. DES and DUL cost $23,468 and $25,979, while yielding 3.05 and 3.16 QALYs, respectively. The incremental cost-effectiveness ratio for DUL compared with DES was $22,867/QALY gained. One-way sensitivity analysis showed that the model was most sensitive to the adherence threshold and utility for mild pain. PSA showed that, at a willingness-to-pay (WTP) of $50,000/QALY, DUL was the most cost-effective option in 56.3% of the simulations, DES in 29.2%, GABA in 14.4%, and PRE in 0.1%. Starting with DUL is the most cost-effective option for PDN when WTP is greater than $22,867/QALY. Decision makers may consider starting with DUL for PDN patients.

Can Chronic Pain Patients Be Adequately Treated Using Generic Pain Medications to the Exclusion of Brand-Name Ones?

According to the Food and Drug Administration (FDA) reports, approximately 8 in 10 prescriptions filled in the United States are for generic medications, with an expectation that this number will increase over the next few years. The impetus for this emphasis on generics is the cost disparity between them and brand-name products. The use of FDA-approved generic drugs saved 158 billion dollars in 2010 alone. In the current health care climate, there is continually increasing pressure for prescribers to write for generic alternative medications, occasionally at the expense of best clinical practices. This creates a conflict wherein both physicians and patients may find brand-name medications clinically superior but nevertheless choose generic ones. The issue of generic versus brand medications is a key component of the discussion of health payers, physicians and their patients. This review evaluates some of the important medications in the armamentarium of pain physicians that are frequently used in the management of chronic pain, and that are currently at the forefront of this issue, including Opana (oxymorphone; Endo Pharmaceuticals, Inc., Malvern, PA), Gralise (gabapentin; Depomed, Newark, CA), and Horizant (gabapentin enacarbil; XenoPort, Santa Clara, CA) that are each available in generic forms as well. We also discuss the use of Lyrica (pregabalin; Pfizer, New York, NY), which is currently unavailable as generic medication, and Cymbalta (duloxetine; Eli Lilly, Indianapolis, IN), which has been recently FDA approved to be available in a generic form. It is clear that the use of generic medications results in large financial savings for the cost of prescriptions on a national scale. However, cost-analysis is only part of the equation when treating chronic pain patients and undervalues the relationships of enhanced compliance due to single-daily dosing and stable and reliable pharmacokinetics associated with extended-duration preparations using either retentive technologies or delayed absorption strategies. Medications given to chronic pain patients should be individualized to best serve analgesic needs and assure patient safety primarily, based on high levels of scientific and economic evidence. Decisions regarding utilization should not be made based solely on limited or faulty assessments of cost-benefit analyses.

Clinical trials supported by the Tinnitus Research Consortium: Lessons learned, the Southern Illinois University experience.

The Tinnitus Research Consortium funded three clinical trials investigating treatments for chronic bothersome tinnitus at Southern Illinois University School of Medicine. The trials were designed to measure the subjective changes in tinnitus distress using standardized questionnaires and objective changes in tinnitus loudness using psychophysical matching procedures. The results of the first two trials have been published and are summarized here. The first trial investigated the effect of gabapentin on the loudness and annoyance of tinnitus in adults with chronic bothersome tinnitus with and without a history of acoustic trauma. A small but significant number of subjects reported decreased tinnitus annoyance that corresponded with a decrease in objective measures of tinnitus loudness during active drug treatment with a washout effect during placebo treatment. The second trial compared the effect of tinnitus retraining therapy (TRT) on adults with normal to near-normal hearing and chronic bothersome tinnitus to treatment with general counseling without acoustic enrichment. Significant improvements in tinnitus severity, but not in objective psychometric measures of tinnitus loudness, occurred in both treatment groups, however a greater effect was observed in the TRT group compared with the control group. The third trial is nearing completion and investigates the long-term results of tinnitus retraining therapy on chronic bothersome tinnitus in adults with hearing loss. Significant lessons and observations on conducting tinnitus clinical trials were learned from these three trials. The challenges of recruiting and retaining study participants is discussed. More importantly, the reliability and stability of the Tinnitus Handicap Inventory (THI) over long intervals is presented. The implications of this variability for the design and interpretation of future tinnitus studies is discussed. This article is part of a Special Issue entitled .

Assessment and treatment of insomnia in adult patients with alcohol use disorders.

Insomnia in patients with alcohol dependence has increasingly become a target of treatment due to its prevalence, persistence, and associations with relapse and suicidal thoughts, as well as randomized controlled studies demonstrating efficacy with behavior therapies and non-addictive medications. This article focuses on assessing and treating insomnia that persists despite 4 or more weeks of sobriety in alcohol-dependent adults. Selecting among the various options for treatment follows a comprehensive assessment of insomnia and its multifactorial causes. In addition to chronic, heavy alcohol consumption and its effects on sleep regulatory systems, contributing factors include premorbid insomnia; co-occurring medical, psychiatric, and other sleep disorders; use of other substances and medications; stress; environmental factors; and inadequate sleep hygiene. The assessment makes use of history, rating scales, and sleep diaries as well as physical, mental status, and laboratory examinations to rule out these factors. Polysomnography is indicated when another sleep disorder is suspected, such as sleep apnea or periodic limb movement disorder, or when insomnia is resistant to treatment. Sobriety remains a necessary, first-line treatment for insomnia, and most patients will have some improvement. If insomnia-specific treatment is needed, then brief behavioral therapies are the treatment of choice, because they have shown long-lasting benefit without worsening of drinking outcomes. Medications work faster, but they generally work only as long as they are taken. Melatonin agonists; sedating antidepressants, anticonvulsants, and antipsychotics; and benzodiazepine receptor agonists each have their benefits and risks, which must be weighed and monitored to optimize outcomes. Some relapse prevention medications may also have sleep-promoting activity. Although it is assumed that treatment for insomnia will help prevent relapse, this has not been firmly established. Therefore, insomnia and alcohol dependence might be best thought of as co-occurring disorders, each of which requires its own treatment.

Experience from therapeutic drug monitoring and gender aspects of gabapentin and pregabalin in clinical practice.

PURPOSE: Gabapentin and pregabalin are antiepileptic drugs (AEDs) with epilepsy and neuropathic pain indications. The purpose of this study was to investigate pharmacokinetic variability of gabapentin and pregabalin and indications for therapeutic drug monitoring (TDM) in clinical practice with focus on gender aspects. METHOD: Anonymous data from routine TDM-service at the National Center for Epilepsy regarding serum concentration measurements of gabapentin and pregabalin, 2009-2013, were utilised. All included samples were drug-fasting in the morning at steady-state. RESULTS: In total, 356 patients were included; gabapentin 189 (66% women), average age 53 years and pregabalin 167 (56% women), average age 50 years. For gabapentin, mean serum concentration/dose(C/D)-ratio was similar across genders. Only 13% of the patients had concentrations above the lower limit of the reference range (70-120 µmol/L), which indicates a need for reevaluation of the reference range. For pregabalin, the C/D-ratio in women (0.08±0.06) was 42% higher than in men (0.056±0.05; p<0.05). The pharmacokinetic variability (C/D-ratio) was >100-fold for both gabapentin and pregabalin. An indication of use (epilepsy/pain/other) was stated in only 26% of the cases (n=94). Epilepsy was assumed as indication when other AEDs were also measured (50% of patients). This was similar for both genders and for both AEDs. Indications for TDM were stated in 155 cases (44%) and were similar for gabapentin and pregabalin. CONCLUSION: Gabapentin and pregabalin are more used in women than in men, and routine use of TDM is most common in patients with epilepsy. Pharmacokinetic variability is extensive, highlighting a need for individualisation of therapy regardless of indication.

A systematic review of pharmacoeconomic studies for pregabalin.

BACKGROUND: With anticonvulsant, anxiolytic, and analgesic properties, pregabalin has been evaluated for neuropathic pain and fibromyalgia (FM). These chronic conditions diminish patients' quality of life and increase healthcare utilization and costs. OBJECTIVE: To assess the current understanding of economic outcomes associated with pregabalin in neuropathic pain and FM. METHODS: Using keywords related to economic outcomes and pregabalin, we systematically searched MEDLINE- and EMBASE-indexed literature and nonindexed "grey" literature on neuropathic pain and FM published from March 2001 to October 2012. Included studies reported economic findings associated with pregabalin. RESULTS: In the past 11 years, 55 publications assessed the direct costs, resource use, or cost-effectiveness of pregabalin for neuropathic pain and FM. Studies generally lacked comparability due to heterogeneous patient populations, assumptions, time periods, and geographies. In the US, following treatment initiation, pregabalin resulted in similar or higher levels of healthcare use for FM compared with duloxetine. In contrast, medical costs for neuropathic pain did not significantly differ after initiation of pregabalin vs. duloxetine or other standard therapies in the US, but in Spain and Sweden, retrospective database studies suggested that pregabalin was cost-saving vs. gabapentin. Few economic analyses estimated indirect costs. CONCLUSIONS: Neuropathic pain and FM are associated with high healthcare resource use and costs. Economic studies of pregabalin in neuropathic pain and FM indicate some results favorable to other forms of care, but heterogeneity among study designs and populations hinder comparisons. Future economic analyses should aim to address data gaps regarding effects of pregabalin on productivity and resource use.

Evidence, regulation and 'rational' prescribing: the case of gabapentin for neuropathic pain.

RATIONALE, AIMS AND OBJECTIVES: In 2004, the pharmaceutical company Warner-Lambert paid US $430 million to resolve criminal and civil legal liability for aggressive off-label marketing of gabapentin. Perhaps surprisingly, however, regulatory and legal concerns regarding the marketing of gabapentin has not significantly impacted upon the attitude of doctors towards using gabapentin for neuropathic pain. In this paper, we attempt to understand the reasons for this discrepancy between clinical practice and regulatory/legal concerns through an analysis of published discussions about gabapentin prescribing. METHODS: We performed a qualitative empirical analysis of the published clinical debate surrounding the use of gabapentin for the management of neuropathic pain. RESULTS: The ongoing use of gabapentin for neuropathic pain was primarily driven by the perception that it was a safe, non-addictive drug with few drug interactions, by possible similarities between the physiology of chronic pain and other neurological conditions, by the well-established clinical precedent of using antiepileptic drugs in pain management, and by the lack of alternative options available in the market. Emerging evidence of lack of effectiveness and controversies about the integrity of the scientific record appeared to be of relatively little importance to practising clinicians. CONCLUSIONS: Those who want to promote 'rational' prescribing need to recognize that prescribing is driven by many factors other than epidemiological data and regulatory indications and that even intensely negative publicity about medicines may not penetrate clinical reasoning. This suggests that a range of measures may be needed to 'incentivize' rational prescribing and to promote research integrity. Regulators must be more sensitive to the contextual issues that are relevant to clinical practice when evaluating drugs for approval and developing guidelines.

Cost-utility of cognitive behavioral therapy versus U.S. Food and Drug Administration recommended drugs and usual care in the treatment of patients with fibromyalgia: an economic evaluation alongside a 6-month randomized controlled trial.

INTRODUCTION: Cognitive behavioral therapy (CBT) and U.S. Food and Drug Administration (FDA)-recommended pharmacologic treatments (RPTs; pregabalin, duloxetine, and milnacipran) are effective treatment options for fibromyalgia (FM) syndrome and are currently recommended by clinical guidelines. We compared the cost-utility from the healthcare and societal perspectives of CBT versus RPT (combination of pregabalin + duloxetine) and usual care (TAU) groups in the treatment of FM. METHODS: The economic evaluation was conducted alongside a 6-month, multicenter, randomized, blinded, parallel group, controlled trial. In total, 168 FM patients from 41 general practices in Zaragoza (Spain) were randomized to CBT (n = 57), RPT (n = 56), or TAU (n = 55). The main outcome measures were Quality-Adjusted Life Years (QALYs, assessed by using the EuroQoL-5D questionnaire) and improvements in health-related quality of life (HRQoL, assessed by using EuroQoL-5D visual analogue scale, EQ-VAS). The costs of healthcare use were estimated from patient self-reports (Client Service Receipt Inventory). Cost-utility was assessed by using the net-benefit approach and cost-effectiveness acceptability curves (CEACs). RESULTS: On average, the total costs per patient in the CBT group (1,847 €) were significantly lower than those in patients receiving RPT (3,664 €) or TAU (3,124 €). Patients receiving CBT reported a higher quality of life (QALYs and EQ-VAS scores); the differences between groups were significant only for EQ-VAS. From a complete case-analysis approach (base case), the point estimates of the cost-effectiveness ratios resulted in dominance for the CBT group in all of the comparisons performed, by using both QALYs and EQ-VAS as outcomes. These findings were confirmed by bootstrap analyses, net-benefit curves, and CEACs. Two additional sensitivity analyses (intention-to-treat analysis and per-protocol analysis) indicated that the results were robust. The comparison of RPT with TAU yielded no clear preference for either treatment when using QALYs, although RPT was determined to be more cost-effective than TAU when evaluating EQ-VAS. CONCLUSIONS: Because of lower costs, CBT is the most cost-effective treatment for adult FM patients. Implementation in routine medical care would require policymakers to develop more-widespread public access to trained and experienced therapists in group-based forms of CBT. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10804772. Registered 29 September 2008.

Pregabalin: a review of its use in adults with generalized anxiety disorder.

Pregabalin (Lyrica(®)), a well established anxiolytic agent, has been approved in the EU for the treatment of generalized anxiety disorder (GAD) in adults. It has a distinct mechanism of action relative to other anti-anxiety agents (α2δ binding at presynaptic voltage dependent calcium channels leading to inhibition of excitatory neurotransmission), a rapid onset of effect (typically ≤1 week) and broad spectrum activity against both the psychic and somatic symptoms of GAD. In long-term studies, pregabalin maintained improvements in anxiety symptoms that occurred in response to short-term treatment and delayed the time to relapse of GAD compared with placebo. Common comorbidities of GAD, such as insomnia, gastrointestinal symptoms and subsyndromal depression, have no effect on the anxiolytic efficacy of, and moreover are specifically improved by, pregabalin. Treatment with pregabalin is generally well tolerated; the drug has an adverse event profile that includes dizziness, somnolence and weight gain. The potential for abuse of pregabalin is low; the risk of withdrawal symptoms is generally low when the drug is discontinued gradually (over 1 week). Alongside selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs), pregabalin is considered a first-line agent for the long-term treatment of GAD by the World Federation of Societies of Biological Psychiatry. It should be stressed, however, that definitive head-to-head studies comparing pregabalin with SSRI/SNRIs, including in patients with GAD and co-morbid major depressive disorder, are currently lacking. Recently, a study of SSRI/SNRI augmentation with pregabalin yielded positive results, while another study of switching from long-term benzodiazepine therapy to pregabalin was inconclusive; further investigations on these topics are warranted.

Activation of mesocorticolimbic reward circuits for assessment of relief of ongoing pain: a potential biomarker of efficacy.

Preclinical assessment of pain has increasingly explored operant methods that may allow behavioral assessment of ongoing pain. In animals with incisional injury, peripheral nerve block produces conditioned place preference (CPP) and activates the mesolimbic dopaminergic reward pathway. We hypothesized that activation of this circuit could serve as a neurochemical output measure of relief of ongoing pain. Medications commonly used clinically, including gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs), were evaluated in models of post-surgical (1 day after incision) or neuropathic (14 days after spinal nerve ligation [SNL]) pain to determine whether the clinical efficacy profile of these drugs in these pain conditions was reflected by extracellular dopamine (DA) release in the nucleus accumbens (NAc) shell. Microdialysis was performed in awake rats. Basal DA levels were not significantly different between experimental groups, and no significant treatment effects were seen in sham-operated animals. Consistent with clinical observation, spinal clonidine produced CPP and produced a dose-related increase in net NAc DA release in SNL rats. Gabapentin, commonly used to treat neuropathic pain, produced increased NAc DA in rats with SNL but not in animals with incisional, injury. In contrast, ketorolac or naproxen produced increased NAc DA in animals with incisional but not neuropathic pain. Increased extracellular NAc DA release was consistent with CPP and was observed selectively with treatments commonly used clinically for post-surgical or neuropathic pain. Evaluation of NAc DA efflux in animal pain models may represent an objective neurochemical assay that may serve as a biomarker of efficacy for novel pain-relieving mechanisms.

Patient demographics and health plan paid costs in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: We determined health plan paid costs and healthcare resource usage of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: CIDP patients from 9 U.S. commercial health plans with claims in 2011 were identified from the Accordant Health Services claims database. We examined demographics, prevalence of comorbidities, prescribed drugs, place of service, and mean annual health plan paid costs per patient. RESULTS: From 6.5 million covered lives, 73 (56% men; mean age 47) met study entry criteria. The most prescribed therapies were intravenous immunoglobulin (IVIg) (26% of patients), gabapentin (26%), and prednisone (16%). The annual health plan paid cost was $56,953. Pharmacy cost was the major cost driver (57% of the total), and IVIg totaled 90% of the pharmacy costs. CONCLUSIONS: Healthcare costs for CIDP patients are substantial, with a large burden in pharmacy usage. Studies are needed to determine optimal long-term treatment strategies for CIDP, particularly related to IVIg.

Potential drug-drug and drug-condition interactions among fibromyalgia patients initiating pregabalin or duloxetine: prevalence and health care expenditure impact.

OBJECTIVE: To quantify the prevalence of potential drug-drug/drug-condition interactions (DDI/DCI) among fibromyalgia patients initiating pregabalin or duloxetine, and to determine the impact of potential DDI/DCI on health care expenditures. DESIGN: Retrospective cohort study. SETTING: U.S. clinical practice, as reflected within a large administrative claims database. SUBJECTS: Fibromyalgia patients newly initiating pregabalin or duloxetine between July 1, 2008 and October 1, 2010 (initiation date = index). OUTCOME MEASURES: Potential DDI measured using clinical software that identifies co-prescription of medications that potentially interact with pregabalin or duloxetine. Potential DCI, drawn from the contraindications and warnings and precautions sections of pregabalin and duloxetine prescribing information, measured using administrative claims-based algorithms. All-cause health care expenditures measured throughout a 6-month postindex period. Analyses included univariate, bivariate, and multivariable statistical approaches. RESULTS: Seven thousand seven hundred fifty-one pregabalin and 7,785 duloxetine initiators were selected for study: mean age 49 years, 88% female. Only 1.4% of pregabalin initiators had ≥1 potential pregabalin DCI; none had potential pregabalin DDI. In contrast, 67% of duloxetine initiators had potential duloxetine DDI/DCI, driven mostly by potential duloxetine DDI (62% of duloxetine initiators). Compared between pregabalin and duloxetine initiators, differences in the prevalence of potential DDI/DCI were statistically significant (P < 0.001). Multivariable analyses indicated that, among duloxetine initiators, those with potential duloxetine DDI/DCI had postinitiation health care expenditures that were $670 higher (P < 0.001) than those without potential duloxetine DDI/DCI. Among pregabalin initiators, potential pregabalin DDI/DCI were not associated with health care expenditures. CONCLUSIONS: Among fibromyalgia patients initiating pregabalin or duloxetine, potential duloxetine DDI could be highly prevalent. Among duloxetine initiators, potential duloxetine DDI/DCI were significantly associated with increased health care expenditures.