pregabalin and Edema

Pregabalin is used in the treatment of postherpetic neuralgia, diabetic neuropathic pain, partial seizures, anxiety disorders and fibromyalgia. Recognized adverse effects associated with its use include cognitive impairment, somnolence and dizziness. Heart failure associated with pregabalin has been described, however the strength of this association has not been well characterized. To examine this further, we will conduct a systematic review of the risk of heart failure and edema associated with use of pregabalin.. We will include all studies (experimental, quasi-experimental, observational, case series/reports, drug regulatory reports) that examine the use of pregabalin compared to placebo, gabapentin or conventional care. Our primary outcome is heart failure and the secondary outcomes include edema and weight gain. We will search electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), and grey literature sources (trial registries, conference abstracts) to identify relevant studies. To ensure literature saturation, we will contact drug manufacturers, conduct forward citation searching, and scan the reference lists of key articles and included studies. We will not restrict inclusion by language or publication status.Two reviewers will screen citations (titles and abstracts) and full-text articles, conduct data abstraction, and appraise risk of bias. Random-effects meta-analysis will be conducted if the studies are deemed heterogeneous in terms of clinical, statistical and methodological factors but still suitable for meta-analysis.. The results of this review will assist physicians to better appreciate pregabalin's risk for edema or congestive heart failure and will be pertinent to the thousands of patients worldwide who are administered this medication.Our protocol was registered in the PROSPERO database (CRD42012002948).

Topics: Edema; gamma-Aminobutyric Acid; Heart Failure; Humans; Outcome Assessment, Health Care; Pregabalin; Research Design; Review Literature as Topic; Risk; Weight Gain

We assessed the efficacy and safety of a flexible-dose pregabalin regimen in patients with diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN) under clinical practice conditions. Further, the trial investigated the correlation of unspecific measures of change (patient and physician global impression of change, PGIC and CGIC) and specific measures of morbidity. The primary outcomes of this prospective, open-label, non-controlled study were the correlation between global status (PGIC and CGIC) and changes in pain, sleep, and anxiety scores as assessed on numerical or visual rating scales. A total of 217 outpatients were included in 53 centres. The most frequently used dosing regimen involved a starting dose of 150mg/d and dose escalation to 300mg/d after one week (mean: 301mg/d, administered in two doses). The significant changes on pain, sleep and anxiety scales (-40%, -43%, -42%) between baseline and study end after 4-week pregabalin treatment were paralleled by the changes in ratings in both the PGIC and CGIC. The correlation with both PGIC and CGIC was 0.60 for pain, 0.51 for sleep and 0.20 or 0.13 for the correlation of anxiety with PGIC and CGIC, respectively. All correlations with exception of the pair CGIC/anxiety reached statistical significance. In conclusion, pregabalin in a flexible-dose regimen improved pain, sleep, anxiety and general state, and was well tolerated. The efficacy and safety profile of pregabalin was consistent with the data from the controlled clinical trials. The PGIC and CGIC and the specific pain and sleep scores, but not the anxiety score were generally well correlated but not synonymous.

Topics: Adolescent; Adult; Aged; Anxiety; Diabetic Neuropathies; Dizziness; Dose-Response Relationship, Drug; Drug Administration Schedule; Edema; Fatigue; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Neuralgia, Postherpetic; Pain Measurement; Patient Satisfaction; Pregabalin; Prospective Studies; Sleep Disorders, Intrinsic; Weight Gain

To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN).. The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement.. Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with >or=30% and >or=50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo (p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo (p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity.. Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.

Topics: Adult; Affect; Aged; Analgesics, Non-Narcotic; Dizziness; Double-Blind Method; Edema; Female; gamma-Aminobutyric Acid; Herpes Zoster; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Pregabalin; Quality of Life; Safety; Sleep Initiation and Maintenance Disorders; Sleep Stages; Treatment Outcome

Topics: Analgesics; Edema; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pregabalin

Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac.. All cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between January 1, 1994 and April 30, 2020 were included to describe their onset patterns (e.g., time to onset). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries and on the electrophysiological properties of rat ventricular cardiomyocytes.. A total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57-85, range 32-95). The median time to onset were 23 days (IQR 10-54) and 17 days (IQR 3-30) for non-cardiogenic edema and acute heart failure, respectively. Cardiogenic and non-cardiogenic peripheral edema occurred frequently after a dose escalation (27/45, 60%), and the course was rapidly favorable after discontinuation of gabapentinoid (median 7 days, IQR 5-13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Acute application of gabapentinoids had no significant effect on Ca. Gabapentinoids can cause concentration-dependent peripheral edema of early onset. The primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Ca

Topics: Aged; Aged, 80 and over; Animal Experimentation; Animals; Edema; Female; Gabapentin; Heart Failure; Humans; Male; Middle Aged; Pharmacovigilance; Pregabalin; Rats

Novel 2,5-dioxoimidazolidine-based conformationally constrained analogues of KN62 (1) were developed as P2X7 receptor (P2X7R) antagonists using a rigidification strategy of the tyrosine backbone of 1. SAR analysis of the 2,5-dioxoimidazolidine scaffold indicated that piperidine substitution at the N3 position and no substitution at N1 position were preferable. Further optimization of the substituents at the piperidine nitrogen and the spacer around the skeleton resulted in several superior antagonists to 1, including 1-adamantanecarbonyl analogue 21i (IC50 = 23 nM in ethidium uptake assay; IC50 = 14 nM in IL-1β ELISA assay) and (3-CF3-4-Cl)benzoyl analogue (-)-21w (54 nM in ethidium uptake assay; 9 nM in IL-1β ELISA assay), which was more potent than the corresponding (+) isomer. Compound 21w displayed potent inhibitory activity in an ex vivo model of LTP-induced pain signaling in the spinal cord and significant anti-inflammatory activity in in vivo models of carrageenan-induced paw edema and type II collagen-induced joint arthritis.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Arthritis, Experimental; Carrageenan; Cattle; Collagen Type II; Drug Discovery; Edema; Enzyme-Linked Immunosorbent Assay; HEK293 Cells; Humans; Hydantoins; Immunoblotting; Inflammation; Interleukin-1beta; Long-Term Potentiation; Macrophages; Male; Mice, Inbred DBA; Molecular Structure; Monocytes; Neuralgia; Purinergic P2X Receptor Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2X7; Structure-Activity Relationship; Sulfonic Acids; Tissue Distribution

Pregabalin is a commonly used therapy currently recommended as first-line treatment for a number of neuropathic pain (NeP) conditions. Since licensure, a number of clinical trials of pregabalin in different NeP conditions have been completed from which additional data on safety and tolerability can be drawn. In this analysis, patient-level data from 31 randomized clinical trials of pregabalin in peripheral NeP sponsored by Pfizer were pooled and assessed for incidence of adverse events (AEs). Incidence by age, disease condition, and race, together with risk differences and time to onset and resolution of AEs, was assessed. In total, 7,510 patients were included: 4,884 on pregabalin (representing 805 patient-years treatment) and 2,626 on placebo. Pregabalin vs. placebo risk analysis identified 9 AEs with a risk difference, for which the lower limit of the 95% confidence interval (CI) was > 1%: dizziness (risk difference [95% CI]: (17.0 [15.4 to 18.6]), somnolence (10.8 [9.5 to 12.1]), peripheral edema (5.4 [4.3 to 6.4]), weight increase (4.7 [3.9 to 5.5]), dry mouth (2.9 [2.1 to 3.8]), constipation (2.3 [1.5 to 3.2]), blurred vision (2.2 [1.6 to 2.9]), balance disorder (2.0 [1.5 to 2.5]), and euphoric mood (1.6 [1.2 to 2.0]). The most common AEs, dizziness and somnolence, typically emerged within the first 1 to 2 weeks of treatment and resolved 1 to 2 weeks later, without resulting in cessation of treatment. The data from this review provide information, indicating which AEs may be expected in patients treated with pregabalin, and suggest that careful dose titration to the highest tolerable dose is the most appropriate approach in clinical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Case-Control Studies; Constipation; Disorders of Excessive Somnolence; Dizziness; Edema; Female; Humans; Male; Middle Aged; Mood Disorders; Neuralgia; Postural Balance; Pregabalin; Sensation Disorders; Vision Disorders; Weight Gain; Young Adult

In this study we aimed to explore the effects of pregabalin on a traumatic brain injury model in rats.. This study included 40 adult male Sprague-Dawley rats randomized into 4 groups, each of which contained equal numbers of animals. The control group had no head trauma and thus was not treated. The trauma group had head trauma but was not treated. The pregabalin group had no head trauma but was treated by pregabalin. The trauma + pregabalin group had head trauma treated with pregabalin. The biopsy samples taken from the study animals were histopathologically examined for the presence of edema, inflammation, and neuronal damage.. All animals in the trauma group had edema, inflammation, and neuronal damage. Four subjects in the control group, 6 in the pregabalin group, and 4 in the trauma + pregabalin group had edema; inflammation was present in 1 subject in the control group, 3 subjects in the pregabalin group, and 3 subjects in the trauma + pregabalin group; neuronal damage existed in 1 subject in the control group, 1 subject in the pregabalin group, and 6 subjects in the trauma+pregabalin group. The trauma group had significantly higher edema and neuronal damage scores than the other groups. Similarly, inflammation was significantly more prevalent in the trauma group than the control and trauma+pregabalin groups.. The results of the present study indicated anti-edema, anti-inflammatory, and neuroprotective effects of pregabalin in an experimental head trauma model in rats. Pregabalin may thus be beneficial in humans with acute TBI by relieving concomitant edema and inflammation.

Topics: Animals; Brain Injuries; Edema; Inflammation; Male; Pregabalin; Rats, Sprague-Dawley

This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund's Adjuvant (CFA). Male Swiss mice received an intraplantar (i.pl.) injection of CFA (50 µl/paw) or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks), and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST) or forced-swimming (FST) depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg), fluoxetine (20 mg/kg) and bupropion (30 mg/kg) significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg), indomethacin (10 mg/kg) and celecoxib (30 mg/kg) markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg) or pregabalin (30 mg/kg) significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg) did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg) was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg), and depression behaviour was prevented by celecoxib (30 mg/kg). The co-treatment with bupropion and celecoxib (3 mg/kg each) significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and anti-inflammatory agents bupropion and celecoxib might represent an attractive therapeutic strategy for depression.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antidepressive Agents; Behavior, Animal; Brain-Derived Neurotrophic Factor; Bupropion; Celecoxib; Cerebral Cortex; Cyclooxygenase 2; Depression; Dipyrone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Edema; Freund's Adjuvant; gamma-Aminobutyric Acid; Inflammation; Interleukin-1beta; Male; Mice; Nociception; Pregabalin; Pyrazoles; Sulfonamides

Topics: Aged; Analgesics; Diagnosis, Differential; Edema; Female; gamma-Aminobutyric Acid; Humans; Neuralgia; Pain Management; Pregabalin

Case report.. To report a case of paraplegia with limb edema caused by pregabalin.. Turkish Armed Forces Rehabilitation Center, Ankara, Turkey.. A 40-year-old male patient with T11 paraplegia had the complaint of swelling in both the lower limbs. He had been given pregabalin because of the neuropathic pain in both the lower limbs. At 10 months, the patient has experienced edema in lower limbs. There was severe edema in both legs, ankles and feet, more evident on the left. Venous Doppler ultrasound was normal on both sides. Blood tests for possible etiologies were normal. No other etiology could be found. The edema was considered to be caused by pregabalin and the medicine was ceased gradually. The edema resolved completely in 2 weeks.. Pregabalin, which is one of medications used for neuropathic pain, might cause limb edema, that is, a condition needs differential diagnosis. This is particularly important for patients with spinal cord injuries (SCIs). Such adverse effect of pregabalin should be kept in mind as an etiology of limb edema in SCI management.

Topics: Adult; Analgesics; Edema; gamma-Aminobutyric Acid; Humans; Lower Extremity; Male; Neuralgia; Paraplegia; Pregabalin; Spinal Cord Injuries

Pregabalin and gabapentin are widely used analgesic, anticonvulsant and anxiolytic agents as they are relatively reliable and easily tolerated. However, they may cause some side effects such as dizziness, somnolence, dose-dependent peripheral edema, and weight gain, which may cause patients to abandon their use. Furthermore, there are a few reports in the literature addressing elderly patients with serious chronic disease and cardiac history, who develop heart failure during pregabalin application. In this report, we present a patient with no cardiac history treated with 300 mg/kg pregabalin due to neuropathic pain, who developed peripheral and then central edema, which were determined after advanced investigations. After stopping pregabalin, the situation regressed. Then, peripheral edema developed associated with the recommended dose of gabapentin, which was used in place of pregabalin. Despite the lack of any published evidence, the New York Heart Association issued a warning about using caution when prescribing pregabalin to type III-IV heart failure patients. Though the effect mechanisms of pregabalin and gabapentin are not well known, the calcium channel relationship may lead to these side effects. In summary, we believe that pregabalin and gabapentin, which is mostly used nowadays, should be administered with care not only in patients with advanced cardiac pathology but also in all patients, due to the potential side effects.

Topics: Amines; Analgesics; Back Pain; Cyclohexanecarboxylic Acids; Diagnosis, Differential; Edema; Female; Gabapentin; gamma-Aminobutyric Acid; Heart Failure; Humans; Middle Aged; Neuralgia; Pregabalin; Tramadol

Topics: Adult; Analgesics; Anxiety Disorders; Edema; Female; gamma-Aminobutyric Acid; Humans; Pregabalin; Premenstrual Syndrome; Young Adult

Topics: Alcoholism; Anticonvulsants; Edema; Female; gamma-Aminobutyric Acid; Humans; Middle Aged; Pregabalin; Substance Withdrawal Syndrome

Cyclooxygenase (COX) contributes to neuropathic pain after peripheral nerve injury, yet COX inhibitors are generally ineffective against mechanical allodynia and hyperalgesia in neuropathic pain patients and animal models. In the present study, we investigated the effects of etodolac, a selective COX-2 inhibitor, on mechanical allodynia in mice after partial sciatic nerve ligation (PSNL) compared to indomethacin (a nonselective COX inhibitor) or celecoxib (a selective COX-2 inhibitor). PSNL decreased the paw-withdrawal threshold (PWT) as assessed by the von Frey hair test, and etodolac, but not indomethacin or celecoxib, administered daily for two weeks, partially or wholly reversed the decrease. The efficacy of etodolac gradually increased throughout the administration period, and the higher dosages restored preligation PWT values by day 21. The positive control pregabalin also partially or wholly reversed the decrease in PWT, but in contrast to etodolac, it showed no increase in efficacy throughout the administration period. In normal mice, etodolac did not affect the PWT, whereas pregabalin increased it. These findings suggest that the mechanisms of inhibition of mechanical allodynia by etodolac and pregabalin are different and demonstrate that in contrast to other COX inhibitors, etodolac is effective against mechanical allodynia in a mouse neuropathic pain model.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Celecoxib; Cyclooxygenase 2 Inhibitors; Edema; Etodolac; gamma-Aminobutyric Acid; Indicators and Reagents; Ligation; Male; Mice; Pain; Pain Measurement; Pregabalin; Pyrazoles; Sciatic Neuropathy; Sulfonamides

We report two patients with refractory epilepsy who developed unilateral painful gynecomastia and lower extremity pain (one of them localized and the other one diffuse), shortly after receiving Pregabalin (PGB). Neither of them had previous endocrinologic problems or complaints about pain on their medical history. PGB was stopped in one patient and reduced in the other one, with complete disparition of the symptoms in the following weeks in both patients. This supports the hypothesis that gynecomastia could be a drug-induced and easy to manage secondary effect of PGB, with a higher incidence than observed on previous clinical trials.

Topics: Adolescent; Anticonvulsants; Edema; Epilepsy; gamma-Aminobutyric Acid; Gynecomastia; Humans; Ilium; Lower Extremity; Magnetic Resonance Imaging; Male; Pain; Pregabalin