pregabalin and Pain--Intractable

The choice of analgesic agent in cirrhotic patients is problematic and must be individualized taking into account several factors including severity of liver disease, history of opioid dependence, and potential drug interactions. With a cautious approach including slow dose up-titration and careful monitoring, effective analgesia can be achieved in most cirrhotic patients without significant side effects or decompensation of their liver disease. Paracetamol is safe in patients with chronic liver disease but reduced doses of 2-3 grams daily is recommended for long-term use. Non-steroidal anti-inflammatory drugs are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Opioids have an increased risk of toxicity particularly in patients with hypoalbuminaemia, and immediate-release as opposed to controlled-release formulations are advised. Co-prescription of laxatives is mandatory to avoid constipation and encephalopathy. Adjuvant analgesics such as tricyclic antidepressants and anti-convulsants may be used cautiously for cirrhotic patients with neuropathic pain. Gabapentin or pregabalin may be better tolerated in cirrhosis because of non-hepatic metabolism and a lack of anti-cholinergic side effects.

Topics: Acetaminophen; Amines; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antidepressive Agents, Tricyclic; Contraindications; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Gabapentin; gamma-Aminobutyric Acid; Humans; Laxatives; Liver Cirrhosis; Neuralgia; Pain Management; Pain, Intractable; Pregabalin

Neuropathic pain associated with postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN) can be intractable and may not respond to commonly used treatments, such as tricyclic antidepressants (TCAs) and opioids. This long-term, open-label study was a preliminary evaluation of pregabalin for patients whose pain had been judged refractory to other treatments for neuropathic pain.. Patients had previously participated in double-blind, placebo-controlled, randomized trials of pregabalin in DPN and PHN. They had moderate to severe neuropathic pain despite treatment with gabapentin, a TCA, and a third medication (e.g., other anticonvulsants, opioid, selective serotonin reuptake inhibitor, tramadol). Flexible-dosage pregabalin 150-600 mg/day was taken for 3-month periods followed by 3- to 28-day pregabalin "drug holidays," with an analysis up to 15 months (five treatment cycles). Pain intensity was measured using the visual analog scale of the Short-Form McGill Pain Questionnaire.. In total, 81 patients were included in this analysis. Pregabalin 150-600 mg/day was associated with clinically meaningful and sustained pain reduction during each treatment cycle. During pregabalin "drug holidays," pain quickly returned to baseline levels; it was reduced again when pregabalin was reinstated.. These results suggest that pregabalin may be beneficial in patients with neuropathic pain who have had an unsatisfactory response to treatment with other medications.

Topics: Analgesics; Diabetic Neuropathies; Double-Blind Method; gamma-Aminobutyric Acid; Humans; Neuralgia; Neuralgia, Postherpetic; Pain Measurement; Pain, Intractable; Placebos; Pregabalin; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Treatment Outcome

To evaluate pregabalin in central neuropathic pain associated with spinal cord injury.. A 12-week, multicenter study of patients randomized to either flexible-dose pregabalin 150 to 600 mg/day (n = 70) or placebo (n = 67), administered BID. Patients were allowed to remain on existing, stable pain therapy. The primary efficacy variable was the endpoint mean pain score, derived from patients' last 7 days daily pain diary entries. Key secondary endpoints included pain responder rates, the SF-MPQ, sleep interference, mood, and the patient global measure of change.. The mean baseline pain score was 6.54 in the pregabalin group and 6.73 in the placebo group. The mean endpoint pain score was lower in the pregabalin group (4.62) than the placebo group (6.27; p < 0.001), with efficacy observed as early as week 1 and maintained for the duration of the study. The average pregabalin dose after the 3-week stabilization phase was 460 mg/day. Pregabalin was significantly superior to placebo in endpoint assessments on the SF-MPQ. The > or =30% and > or =50% pain responder rates were higher with pregabalin than placebo (p < 0.05). Pregabalin was associated with improvements in disturbed sleep (p < 0.001) and anxiety (p < 0.05), and more patients reported global improvement at endpoint in the pregabalin group (p < 0.001). Mild or moderate, typically transient, somnolence and dizziness were the most common adverse events.. Pregabalin 150 to 600 mg/day was effective in relieving central neuropathic pain, improving sleep, anxiety, and overall patient status in patients with spinal cord injury.

Topics: Adult; Affect; Aged; Aged, 80 and over; Analgesics; Anxiety; Disability Evaluation; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Pain Threshold; Pain, Intractable; Placebos; Pregabalin; Sleep Initiation and Maintenance Disorders; Spinal Cord Injuries; Treatment Outcome

Systemic amyloidosis is a disease that often involves multiple organ systems, including the peripheral nervous system. Patients may present with severe, refractory neuropathic pain; however, the optimal treatment approach for pain for these patients remains unclear.. A man with severe, refractory neuropathic pain in his bilateral upper and lower extremities and the trunk secondary to amyloid neuropathy is presented. Multiple medication trials, including neuropathic and opioid agents, produced considerable adverse effects and minimal relief. Scrambler therapy, a novel electrical stimulation modality, was used and was associated with substantial short-term but nonsustained benefit. Spinal cord stimulation was considered, but given his diffuse symptoms, it was deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery system was placed with infusion of hydromorphone, resulting in substantial pain reduction in all involved areas and with an improved adverse effect profile. This intervention resulted in immense improvement in the patient's quality of life, despite progression of his systemic amyloidosis.. Severe pain in the setting of amyloid neuropathy is often difficult to treat. To our knowledge, this represents the first report of Scrambler therapy or an implanted intrathecal drug delivery system used for a patient with refractory amyloidosis-related neuropathic pain, resulting in substantial analgesic benefit and improved quality of life.

Topics: Amyloid Neuropathies; Analgesics; Humans; Infusion Pumps, Implantable; Injections, Spinal; Male; Middle Aged; Neuralgia; Pain Management; Pain Measurement; Pain, Intractable; Pregabalin

Topics: Aged; Calcium Channel Blockers; Depressive Disorder; Duloxetine Hydrochloride; Female; Humans; Pain, Intractable; Pregabalin; Psychiatric Status Rating Scales; Tramadol; Treatment Outcome

To describe clinical and resource utilization patterns in patients with refractory neuropathic pain (NeP) who were prescribed pregabalin for the first time in routine medical practice in primary care settings.. Post-hoc analysis of a 12-week prospective observational study including pregabalin naïve adult patients with refractory chronic NeP of at least 6-months duration. Self-reported pain intensity, disability, sleep disturbances, symptoms of anxiety and depression, disability, health-related quality of life (HRQoL), health care resource utilization, and corresponding costs were assessed in this post-hoc analysis.. One thousand three hundred fifty-four patients were enrolled in the study, and three treatment groups were identified: (1) 598 patients replaced prior pain treatments with pregabalin as monotherapy; (2) 589 added pregabalin to their existing pain treatments; and (3) 167 other pain treatments were prescribed according with physician routine medical practice. Statistically significant differences were reported at baseline for intensity of pain, patient disability, severity of depressive symptoms, and HRQoL (P < 0.01 in all cases). No statistically significant differences were reported among the three treatment groups for anxiety severity or sleep disturbances. Subjects who received add-on pregabalin had greater use of direct and indirect resources vs the other groups, resulting in significantly higher quarterly overall costs per patient: €2,397 (2,308), €2,470 (1,857), and €3,110 (2,496), respectively (P < 0.001).. These findings suggest that primary care physicians chose pregabalin as an option for treating refractory patients who tended to have much more severe NeP profiles, costing society more than when they chose other therapeutic strategies not including pregabalin.

Topics: Adult; Aged; Analgesics; Female; gamma-Aminobutyric Acid; Health Care Costs; Humans; Male; Middle Aged; Neuralgia; Pain, Intractable; Practice Patterns, Physicians'; Pregabalin; Primary Health Care; Spain; Surveys and Questionnaires

A small but significant proportion of patients with peripheral neuropathic pain (NeP) are refractory to the typical treatments applied in clinical practice, including amitriptyline and gabapentin. Thus, they continue to suffer the debilitating effects of NeP. This study aimed to evaluate the cost-effectiveness of pregabalin in comparison to usual care, in patients with refractory NeP, from a third party payer's perspective (NHS).. A stochastic simulation model was constructed, using clinical data from four non-randomized studies, to generate pain pathways of patients receiving usual care and pregabalin. Treatment effect (pain reduction) was converted to quality-of-life (QoL) data, using a regression analysis based on new utility data, collected from a survey of refractory NeP patients presenting to pain clinics in Cardiff, Wales. All relevant direct costs were estimated using resource use from the survey data (where available) and unit costs from the British National Formulary (BNF). The analysis was run over a 5-year time horizon, with costs and benefits discounted at 3.5%.. The use of non-randomized (observational) data to characterize the effectiveness of treatments for NeP. Exclusion of productivity costs and consequences from the analysis.. In the base case analysis, an incremental cost-effectiveness ratio (ICER) of £10,803 per quality adjusted life year (QALY) was attained. This result was found to be reasonably insensitive to variations in the key input parameters, with ICERs ranging from £8505 to £22,845 per QALY gained.. The analysis shows that pregabalin is a cost-effective alternative to usual care in patients with refractory NeP, with an ICER well below the threshold typically adopted by UK health technology assessment groups, such as NICE.

Topics: Analgesics; Cost-Benefit Analysis; Female; gamma-Aminobutyric Acid; Humans; Male; Neuralgia; Pain, Intractable; Pregabalin; Quality-Adjusted Life Years; State Medicine; Stochastic Processes; United Kingdom

Spinal cord injury (SCI) pain in humans is difficult to treat, and the lack of valid methods to measure behavior comparable to the complex human pain experience preclinically represents an important obstacle to finding better treatments for this type of central pain. The place escape/avoidance paradigm (PEAP) relies on the active choice of an animal between its natural preference for a dark environment or pain relief, and it has been suggested to measure the affective-motivational component of pain. We have modified the method to a T10 spinal cord contusion model (SCC) of at-level central neuropathic pain in Sprague-Dawley rats. In order to demonstrate sensitivity to change in escape/avoidance behavior and thus the applicability of the PEAP method to predict drug efficacy, we investigated the effect of pregabalin (30 mg/kg) treatment in a randomized design. SCC animals displayed increased escape/avoidance behavior postinjury, indicating at-level mechanical hypersensitivity. Second, we found no correlation between state anxiety levels in SCC animals (elevated plus maze) and PEAP behavior, suggesting that the PEAP measurement is not biased by differences in anxiety levels. Third, we demonstrated a decrease in escape/avoidance behavior in response to treatment with the analgesic drug pregabalin. Thus, the PEAP may be applicable as a surrogate correlate of human pain. In conclusion, the primary finding in this study was a sensitivity to change in escape/avoidance behavior induced by pharmacological modulation with analgesics, supporting the use of the PEAP as a central outcome measure in preclinical SCI pain research.

Topics: Analgesics; Animals; Anxiety; Avoidance Learning; Behavior, Animal; Disease Models, Animal; Fear; Female; gamma-Aminobutyric Acid; Neuropsychological Tests; Outcome Assessment, Health Care; Pain, Intractable; Pregabalin; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

Conventional approaches to the management of neuropathic pain (NeP) often yield unsatisfactory results. We aimed to investigate pregabalin, a gamma-aminobutyric acid (GABA)-analogue, in a wide range of pregabalin naive patients with treatment refractory NeP.. Investigator-initiated, 4-week, open, prospective multicentre study in tertiary care. Pregabalin was prescribed at physicians' discretion based on patients' individual responses and tolerability, with or without concomitant analgesics. Consecutive patients were requested to fill in questionnaires at baseline and after 14 and 28 days with numerical pain rating scales (0, none; 10, worst possible), sleep rating scales, parts of the Brief Pain Inventory, Pain Experience Scale, Short Questionnaire on Current Burden and the SF-12 health-related quality of life scale.. In 55 patients, the mean pregabalin dose was 142 +/- 26 mg at day 1 and 348 +/- 161 mg at day 28. The mean pain score decreased from 6.5 +/- 1.7 to 5.5 +/- 1.9 at day 14 and to 4.9 +/- 1.8 at day 28 (-24.6%, p < 0.0001). Significant and rapid improvements were noted in the sleep interference score (p < 0.00001), Short Questionnaire on Current Burden (p < 0.01) and SF-12 (somatic score p < 0.001; psychological score p < 0.01). Pregabalin was well tolerated, and only three patients (5%) discontinued treatment prematurely.. Our findings suggest that pregabalin is an effective and well-tolerated drug in difficult-to-treat NeP patients under daily clinical practice conditions. A flexible dosing approach appears appropriate to ensure patient compliance and treatment success.

Topics: Adult; Aged; Analgesics; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain Measurement; Pain, Intractable; Peripheral Nervous System Diseases; Pregabalin; Quality of Life; Treatment Outcome