[Interventional effect and inflammatory regulation mechanism of dihydroartemisinin combined with pregabalin on neuropathic pain mice].

This study aims to clarify the effects of dihydroartemisinin(DHA) combined with pregabalin(PGB) on neuropathic pain(NP) in mice and explore the neuroinflammatory regulatory mechanism. NP mice model was established using spinal nerve ligation, whereas the sham group exposed the spinal nerve without ligation. The mice were randomly divided into sham group, model group, PGB groups of low, medium, and high doses(PGB-L, PGB-M, and PGB-H, with 22, 45, and 91 mg·kg~(-1)), DHA group(16 mg·kg~(-1)), and DHA combined with PGB groups of low, medium, and high doses(DHA + PGB-L, DHA + PGB-M, and DHA + PGB-H). Administration by gavage 18 days after modeling. Von Frey and cold plate were used to detect mechanical pain threshold and cold pain sensitivity in mice. The tail suspension test and forced swimming test were used to investigate depressive behavior, and the open field test was used to estimate anxiety behavior. The Morris water maze was used to evaluate cognitive function. Liquid suspension chip technology was used to quantitatively analyze immune inflammation-related factors. Immunofluorescence was used to detect the expression of CC chemokine ligand 3(CCL3) and transmembrane protein 119(TMEM119). The results showed that compared with the sham group, the mechanical pain and cold pain sensitivity thresholds of the model group were significantly reduced, and the struggle time was significantly increased in the tail suspension test and forced swimming test. The activity time in the central area was significantly reduced in the open field test. The residence time in the second/fourth quadrant was significantly longer than that in other quadrants, and the latency time of platform climbing significantly increased after platform withdrawal in the Morris water maze experiment. The expression of CCL3 was significantly increased; the number of TMEM119 positive cells and the cell body area were significantly increased. Compared with the model group, the DHA + PGB-M group showed a significant increase in mechanical pain and cold pain sensitivity thresholds, as well as a significant increase in struggle time in the tail suspension test and forced swimming test. The activity time in the central area of the open field test was significantly reduced. The residence time in the second/fourth quadrant was significantly shorter than that in other quadrants, and the latency time of platform climbing after platform withdrawal was significantly reduced. Compared with the PGB-M group, the mechanical pain threshold of D14-17 in the DHA + PGB-M group was significantly increased, and the struggle time during forced swimming was significantly increased. The residence time in the second/fourth quadrant of the Morris water maze was significantly shorter than that in other quadrants. Compared with the model group, the expression of CCL3, the number of TMEM119 positive cells, and the cell body area in the DHA + PGB-M group were significantly decreased. This study indicates that DHA + PGB can enhance the analgesic effect of PGB on NP mice, break through the limitations of PGB tolerance, and make up for the shortcomings of PGB in antidepressant and cognitive improvement. Its mechanism may be related to regulating neuroinflammation by inhibiting the activation of microglial cells and expression of CCL3.

Pregabalin-induced delayed cutaneous hypersensitivity reaction occurring after 40 days of use: a case report.

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia. A drug provocation test for pregabalin was positive. The time interval between initiating medication and the onset of the patient's rash was the longest and he also had the largest area of skin affected compared with patients with a similar condition in previous related reports. Remaining vigilant for possible adverse cutaneous hypersensitivity reactions during treatment is important because of the long-term course of pregabalin treatment for neuropathic pain.

Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

Diabetic Peripheral Neuropathy: Prevention and Treatment.

Diabetic peripheral neuropathy occurs in up to 50% of patients with diabetes mellitus and increases the risk of diabetic foot ulcers and infections. Consistent screening and clear communication are essential to decrease disparities in assessment of neuropathic symptoms and diagnosis. Physicians should address underlying risk factors such as poor glycemic control, vitamin B12 deficiency, elevated blood pressure, and obesity to reduce the likelihood of developing neuropathy. First-line drug therapy for painful diabetic peripheral neuropathy includes duloxetine, gabapentin, amitriptyline, and pregabalin; however, these medications do not restore sensation to affected extremities. Evidence for long-term benefit and safety of first-line treatment options is lacking. Second-line drug therapy includes nortriptyline, imipramine, venlafaxine, carbamazepine, oxcarbazepine, topical lidocaine, and topical capsaicin. Periodic, objective monitoring of medication response is critical because patients may not obtain desired pain reduction, adverse effects are common, and serious adverse effects can occur. Opioids should generally be avoided. Nondrug therapies with low- to moderate-quality evidence include exercise and neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation. Peripheral transcutaneous electrical nerve stimulation is well tolerated and inexpensive, but benefits are modest. Other treatments, such as acupuncture, alpha-lipoic acid, acetyl-L-carnitine, cannabidiol, and onabotulinumtoxinA need further study in patients with diabetic peripheral neuropathy.

Pregabalina preoperatoria previene las fasciculaciones y mialgias inducidas por succinilcolina: metaanálisis de ensayos aleatorizados / Preoperative pregabalin prevents succinylcholine-induced fasciculations and myalgias: A meta-analysis of randomized trials

La succinilcolina es el bloqueador neuromuscular de referencia para la inducción de secuencia rápida. Sin embargo, su uso se asocia a fasciculaciones y mialgias. Se realizó una revisión sistemática y un metaanálisis. Se incluyeron ensayos clínicos controlados aleatorizados comparando gabapentinoides frente a placebo, para la prevención de fasciculaciones y mialgias inducidas por succinilcolina. Se incluyeron seis estudios clínicos aleatorizados. El número total de pacientes fue de 481, de los cuales 241 se incluyeron en el grupo de intervención y 240 en el grupo de placebo. Los gabapentinoides redujeron la incidencia de mialgia inducida por succinilcolina (RR=0,69; IC95%: 0,56-0,84; p<0,001), que siguió siendo estadísticamente significativa para pregabalina (RR=0,71; IC95%: 0,54-0,93; p=0,013) y gabapentina (RR=0,61; IC95%: 0,45-0,82; p=0,001) por separado. No hubo diferencia entre los grupos en cuanto a fasciculaciones (RR=0,92; IC95%: 0,82-1,03; p=0,148). El uso preoperatorio de gabapentinoides se asocia a una menor incidencia de mialgias inducidas por succinilcolina dentro de las primeras 24horas posteriores al procedimiento. (AU)

Succinylcholine is the gold standard neuromuscular blocker for rapid sequence induction, however, its use is associated with fasciculations and myalgias. A systematic review and meta-analysis including randomized controlled clinical trials was performed comparing gabapentinoids versus placebo for the prevention of fasciculations and succinylcholine-induced myalgias. Six randomized clinical studies were included. The total number of patients was 481, of which 241 were in the intervention group and 240 in the placebo group. Gabapentinoids reduced the incidence of succinylcholine-induced myalgia (RR=.69; 95%CI: .56-.84; P<.001), which remained statistically significant for pregabalin (RR=.71; 95%CI: .54-.93; P=.013) and gabapentin (RR=.61; 95%CI: .45-.82; P=.001) separately. There was no difference between the groups in fasciculations (RR=.92; 95%CI: .82-1.03; P=.148). Preoperative use of gabapentinoids is associated with lower incidence of succinylcholine-induced myalgias within the first 24hours after the procedure. (AU)

Pregabalin Adjuventia Helped Risperidone-Induced Extrapyramidal Syndrome and Augmented Antipsychotic Response in an Adolescent with Schizophrenia.

Here, authors report on an interesting case of early-onset of schizophrenia where adjunctive pregabalin alleviated risperidone-induced pseudoparkinsonism, helped with insomnia and agitation and boosted antipsychotic response with great tolerability. We wager that gabapentenoids can be a viable option in the niche of psychopharmacotherapy of schizophrenia in CAP population.

Influence of the calcium voltage-gated channel auxiliary subunit (CACNA2D1) absence on intraocular pressure in mice.

The etiology of elevated intraocular pressure (IOP), a major risk factor for glaucoma (optic nerve atrophy), is poorly understood despite continued efforts. Although the gene variant of CACNA2D1 (encoding α2δ1), a calcium voltage-gated channel auxiliary subunit, has been reported to be associated with primary open-angle glaucoma, and the pharmacological mitigation of α2δ1 activity by pregabalin lowers IOP, the cellular basis for α2δ1 role in the modulation of IOP remains unclear. Our recent findings reveled readily detectable levels of α2δ1 and its ligand thrombospondin in the cytoskeletome fraction of human trabecular meshwork (TM) cells. To understand the direct role of α2δ1 in the modulation of IOP, we evaluated α2δ1 null mice for changes in IOP and found a moderate (∼10%) but significant decrease in IOP compared to littermate wild type control mice. Additionally, to gain cellular insights into α2δ1 antagonist (pregabalin) induced IOP changes, we assessed pregabalin's effects on human TM cell actin cytoskeletal organization and cell adhesive interactions in comparison with a Rho kinase inhibitor (Y27632), a known ocular hypotensive agent. Unlike Y27632, pregabalin did not have overt effects on cell morphology, actin cytoskeletal organization, or cell adhesion in human TM cells. These results reveal a modest but significant decrease in IOP in α2δ1 deficient mice, and this response appears to be not associated with the contractile and cell adhesive characteristics of TM cells based on the findings of pregabalin effects on isolated TM cells. Therefore, the mechanism by which pregabalin lowers IOP remains elusive.

Stellate Ganglion Destruction With Alcohol Versus Thermal Ablation for Chronic Post-Mastectomy Pain: A Randomized Trial.

BACKGROUND: Post-mastectomy pain syndrome (PMPS) is a persistent post-surgical neuropathic pain. Stellate ganglion (SG) block is used for diagnosis, prognosis, and treatment of pain syndrome. OBJECTIVES: We aimed to evaluate the efficacy of SG destruction with alcohol versus thermal ablation for PMPS management. STUDY DESIGN: Randomized, double-blind clinical trial. SETTING: National Cancer Institute, Cairo University, Egypt. METHODS: Female patients aged 20-65 years who underwent breast cancer surgery and suffered moderate to severe pain for more than 6 months were categorized equally into 2 groups. SG destruction was with ultrasound (US) guidance and C7 level confirmation by fluoroscopy either by alcohol injection in Group A or thermal ablation with a time of 60 seconds at 80ºC repeated twice in Group B. Follow-up was at 1, 4, 8, and 12 weeks. RESULTS: Visual analog scale (VAS) measurements after 1, 4, 8, and 12 weeks were significantly lower than pre-procedure measurements in both groups (P value < 0.001). There was a significant reduction in VAS score after 4 and 8 weeks in Group A than in Group B (P value = 0.003 and 0.018). Oxycodone and pregabalin consumption after 4 and 8 weeks were significantly lower in Group A than in Group B. Physical health, mental health, and satisfaction scores were comparable. There were no significant complications in both groups. LIMITATIONS: The relatively small sample size and short follow-up period are limitations to our study. CONCLUSION: US-guided SG destruction with alcohol was more effective than thermal radiofrequency for managing acute postoperative pain by decreasing pain score, oxycodone, and pregabalin consumption, which were consumed before the block.

Methamphetamine as the most common concomitant substance used with pregabalin misuse.

BACKGROUND AND AIM: Non-medical use of Pregabalin (PGB) is a growing concern in many countries because of the serious consequences associated with their abuse. Judicial cases within the probation system, multiple drug users, and patients in treatment programs administered PGB at higher doses than suggested, commonly without prescription. For this reason, it is important to analyze PGB by adding it to the routine analysis scale in determining whether PGB is used for medical purposes or abuse. In this study, PGB analyzed (single or multiple substance use, concomitant substances) in urine samples of forensic and clinical cases by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition to the sociodemographic and clinical characteristics of pregabalin-positive cases, the results were evaluated separately from a clinical and forensic perspective. METHODS: All urine samples which was admitted to Addiction Toxicology Laboratory from 'drug abuse probation system' (forensic cases, n = 640) and from various departments of our hospital (clinical cases, n = 371) between December 2022 and April 2023. Screening analysis were carried out by immunoassay in total 1011 cases. LC-MS/MS method simultaneously analyzed amphetamine, benzoilecgonine, cocaine, codeine, metamphetamine, morphine, 3,4-metilenedioksi-N-metilamfetamin (MDMA), 11-nor-9-karboksi-Δ9-tetrahidrokannabinol and pregabalin in urine samples. PGB was added to the our routine substance screening analysis scale in December 2022 to detect pregabalin use. RESULTS: PGB was detected in 12.3% of probabition cases and 13.2% of clinical cases. The mean age of PGB positive cases was 26.55 ± 7,52 years old, predominantly males (%85,9). Single PGB was detected in 53.2% of forensic cases (n = 42), and 38.7% of clinical cases (n = 19). The most common substance detected concomitantly with PGB was amphetamine type stimulants (ATSs:amphetamine, methamphetamine, ecstasy/MDMA etc.) (22.8% of forensic cases and 46.9% of clinical cases), followed by concomitant cannabis use (24.1% of forensic cases and 26.5% of clinical cases). Concomitant opioid use was rare (1.3% of forensic cases and 4.1% of clinical cases). Detection of PGB was significantly different across months on which the samples were collected (x2 = 82.8, df=4, p < 0.001). CONCLUSION: Inconsistently with previous studies suggesting opioids as the most prevalant substances concominant with PGB, our results showed that stimulants (especially ATSs) were the most prevelant substances concominant with PGB, followed by cannabis. High proportion of PGB detection in probabition cases, frequently as a single substance abuse takes attention. These results suggest that PGB, may be used to avoid legal consequences. It is important for laboratories to be aware that they need to make changes as addition of newly abused substances in their analysis panels, when necessary, as differences between regions and cultures affect substance use patterns.

Edema related to treatment with psychotropic drugs.

Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries ("Arzneimittelsicherheit in der Psychiatrie", AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46‰ of patients treated with pregabalin, followed by mirtazapine (0.8‰). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.

Trends in Pregabalin Use and Prescribing Patterns in the Adult Population: A 10-Year Pharmacoepidemiologic Study.

BACKGROUND AND OBJECTIVE: Pregabalin is steadily gaining popularity worldwide, with epidemiological studies indicating an increase in labeled, off-labeled, and recreational uses. In Israel, pregabalin prescriptions are not regulated by the controlled substances legislations, prompting a need to examine its usage trends for potential policy adjustments. The objective of this study was to assess trends in pregabalin prescribing during a 10-year period, to characterize demographic and clinical characteristics of individuals prescribed pregabalin, and to identify risk factors associated with high-intensity pregabalin use. METHODS: This retrospective, longitudinal study examined trends in pregabalin prescribing from 2010 to 2019 based on data extracted from the Clalit Health Services (CHS) electronic database. Annual pregabalin prescribing rate was calculated individually for each reporting year. A univariable analysis was conducted to compare the demographic and clinical characteristics of pregabalin users in 2019 with those in 2010. Multivariable regression analysis was performed to assess dose-related patterns by specific demographic and clinical characteristics. RESULTS: Pregabalin prescription rate more than doubled over 10 years [odds ratio (OR) 2.3, p = 0.001], reaching 7.2 [95% confidence interval (CI) 7.18-7.28] prescriptions per 100 CHS members in 2019. The highest prescription rates were observed among the elderly population (13.2 and 24.1 prescriptions per 100 CHS members for those aged 55-74 and over 75 years old, respectively). Same-year administration of pregabalin with opioids, benzodiazepines, and Z-drugs was common; however, the percentage of patients using these drugs together declined in 2019 compared with 2010 (p < 0.001). Males, patients with low socioeconomic status, patients aged 35-54 years, and those who consumed opioids, benzodiazepines, and Z-drugs received higher pregabalin doses. CONCLUSION: Pregabalin use has increased significantly in the Israeli adult-based CHS population, consistent with worldwide data. A growing use over time may indicate overprescription. More studies are needed on misuse patterns to identify populations most susceptible to high-dose and high-intensity pregabalin use.

The efficacy of pregabalin for pain control after thoracic surgery: a meta-analysis.

BACKGROUND: Pregabalin may have some potential in alleviating pain after thoracic surgery, and this meta-analysis aims to explore the impact of pregabalin on pain intensity for patients undergoing thoracic surgery. METHODS: PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of pregabalin on pain intensity after thoracic surgery. RESULTS: Five RCTs were finally included in the meta-analysis. Overall, compared with control intervention for thoracic surgery, pregabalin was associated with significantly reduced pain scores at 0 h (mean difference [MD]=-0.70; 95% confidence interval [CI]=-1.10 to -0.30; P = 0.0005), pain scores at 24 h (MD=-0.47; 95% CI=-0.75 to -0.18; P = 0.001) and neuropathic pain (odd ratio [OR] = 0.24; 95% CI = 0.12 to 0.47; P < 0.0001), but demonstrated no obvious impact on the incidence of dizziness (OR = 1.07; 95% CI = 0.15 to 7.46; P = 0.95), headache (OR = 1.00; 95% CI = 0.30 to 3.35; P = 1.00) or nausea (OR = 1.24; 95% CI = 0.46 to 3.35; P = 0.68). CONCLUSIONS: Pregabalin may be effective to alleviate the pain after thoracic surgery.

Efficacy and safety of pregabalin vs carbamazepine in patients with central post-stroke pain.

OBJECTIVE: To compare the efficacy and safety of pregabalin and carbamazepine in patients with central post-stroke pain (CPSP). METHODS: Patients included in the study were randomly assigned to either flexible-dose pregabalin treatment group or carbamazepine treatment group. The primary efficacy variable was face visual analog scale (F-VAS), the second efficacy assessment was used to assess the effect of treatment on mental health by Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD). RESULTS: The mean baseline pain score F-VAS was 6.47 in the pregabalin group and 6.58 in carbamazepine treatment group. F-VAS was significantly lower in the pregabalin group (1.64) than (3.94) carbamazepine treatment group after treatment. Pregabalin was significantly superior to carbamazepine in endpoint assessments on the HAMA and HAMD after treatment. F-VAS and HAMD were showed efficacy as early as week 2 and maintained for whole duration of the study. The average pregabalin dose in the 12-week study was 214.6 (150-375) mg/day. The mean dose (range) of carbamazepine received by the patients was 275.0 (200-400) mg/day. Mild or moderate, typically transient, somnolence and dizziness were the most common adverse events (AES). The differences of the side effects between the two groups were not significant. CONCLUSIONS: Pregabalin, but not carbamazepine, may be effective in improving F-VAS, HAMA and HAMD in patients with CPSP.

Gabapentinoids and lactation: Review of the literature.

Gabapentin and pregabalin, which belong to the gabapentinoid drug family, are widely used, especially in neuropathic pain treatment, due to their effectiveness in pain management. Although many of the comorbidities and symptoms that limit the use of gabapentinoids are clearly described in the literature, there is limited data on their use during lactation. A 33-year-old female patient was admitted to our clinic with neuropathic pain and muscle weakness in her left lower extremity following spinal anesthesia for a cesarean section. We aimed to present the gabapentin treatment of a breastfeeding patient with persistent neuropathic pain in light of a literature review.

Pregabalin Does Not Increase Risk of Heart Failure Exacerbation in Patients With Pre-existing Heart Failure.

BACKGROUND: Through actions of calcium channel trafficking inhibition and sodium/water retention, pregabalin may increase the risk of acute heart failure (AHF). OBJECTIVE: The objective of this study was to determine the prevalence of heart failure (HF) acute exacerbations, measured by a composite of emergency department (ED) visits, per-patient per-year (PPPY) hospitalizations, time-to first ED admission, and time-to hospitalizations in pre-existing HF patients taking pregabalin compared with those who were pregabalin-naive. METHODS: A retrospective cohort study of pregabalin users with HF were propensity score-matched to pregabalin-naïve patients with HF to evaluate the composite of ED admissions or PPPY hospitalizations, time-to first ED admission, and time-to hospitalizations during the 365 days post-index. Doubly robust generalized linear regression and Cox-proportional hazard regression modeling were undertaken for analysis of differences between groups. RESULTS: The matched cohort of 385 pregabalin users and 3460 pregabalin nonusers were principally middle-aged, equally gender distributed, and primary Caucasian. Most patients were on guideline-directed HF medical therapy. The estimated cumulative incidence of the primary outcome was a hazard ratio of 1.099 (95% CI: 0.789-1.530; P = 0.58). CONCLUSION AND RELEVANCE: This large, single-center, cohort study shows pregabalin is not associated with an increased risk of AHF events in patients with pre-existing HF.

Perioperative Implementation of Low-Dose Pregabalin in an Enhanced Recovery After Cardiac Surgery Protocol: A Pre-Post Observational Study.

OBJECTIVES: Determine the effect of low-dose pregabalin in the perioperative enhanced recovery after cardiac surgery protocol. DESIGN: Pre-post observational study. SETTING: Tertiary care hospital. PARTICIPANTS: Patients undergoing off-pump coronary artery bypass graft procedures. INTERVENTIONS: Pregabalin 75 mg BID for 48 hours postoperatively versus no pregabalin in a perioperative setting. MEASUREMENTS AND MAIN RESULTS: Perioperative opioid use, pain scores, length of stay, time to extubation, and mortality were all measured. Descriptive data were presented as mean (SD), median (IQR), or N (%). Ordinal and continuous data used the t-test or Kruskal-Wallis test. Categorical data were compared between groups using the chi-square test or Fisher's exact test, as appropriate. Low-dose pregabalin administration (75 mg twice daily for 48 hours after surgery) was associated with a clinically significant reduction in opioid consumption on postoperative day 0 by 30.6%, with a median requirement of 318 (233, 397) morphine milligram equivalents (MME) in the pregabalin group compared with 458 (375, 526) MME in the control group (p < 0.001). There was no significant difference in pain scores between the groups with the exception at 0-to-12 hours, during which the pregabalin group had greater pain scores (median 3.32 [1.65, 4.36] v 2.0 [0, 3.25], p = 0.013) (Table 3). Moreover, there was no significant difference in pain scores on postoperative day 1 (p = 0.492), day 2 (p = 0.442), day 3 (p = 0.237), and day 4 (p = 0.649). The difference in average Richmond Agitation Sedation Score scores was also not statistically significant between groups at 12 hours (p = 0.954) and at 24 hours (p = 0.301). The pregabalin group had no increased incidence of adverse events or any significant differences in intensive care unit length of stay, time to extubation, or mortality. CONCLUSIONS: In this evaluation of perioperative pregabalin administration for patients requiring cardiac surgery, pregabalin reduced postoperative opioid use, with significant reductions on postoperative day 0, and without any significant increase in adverse reactions. However, no differences in intensive care unit length of stay, time to extubation, or mortality were noted. The implementation of low-dose perioperative pregabalin within an Enhanced Recovery After Cardiac Surgery protocol may be effective at reducing postoperative opioid use in the immediate postoperative period, and may be safe with regard to adverse events. Ideal dosing strategies have not been determined; thus, further randomized control trials with an emphasis on limiting confounding factors need to be conducted.

Managing delayed or missed pregabalin doses in patients with focal epilepsy: a Monte Carlo simulation study.

BACKGROUND: Delayed or missed doses are inevitable in epilepsy pharmacotherapy. The current remedial measures recommended by the United States Food and Drug Administration (FDA) for non-adherence are generic and lack clinical evidence. AIM: To assess remedial strategies for delayed or missed pregabalin doses in patients with epilepsy using Monte Carlo simulations. METHOD: Monte Carlo simulations were performed using a published population pharmacokinetic model for pregabalin. The applicability of five proposed remedial regimens as well as FDA recommendations was evaluated by simulating various poor adherence scenarios in eight populations, including those with renal dysfunction. RESULTS: All proposed remedial strategies were associated with delay duration and renal function. When delays are relatively short, an immediate regular dose is advised. The cut-off time points for taking the regular dose as a remedial regimen were 1, 2, 4, and 12 h for patients with mild renal impairment and normal renal function, moderate renal impairment, severe renal impairment, and end-stage renal disease, respectively. However, when delay aligns closely with a dosing interval, a regular dose combined with a partial dose proves effective. Generally, supplementing 1.3-fold the regular dose at the next scheduled time adequately compensates for the missed dose. CONCLUSION: Model-based simulations provided quantitative evidence for the effectiveness and feasibility of remedial strategies for missed or delayed pregabalin doses.

Randomized, double-blind, controlled trial of a combination of alpha-lipoic acid and pregabalin for neuropathic pain: the PAIN-CARE trial.

ABSTRACT: We compared a combination of the nonsedating antioxidant, alpha-lipoic acid (ALA), with the sedating anticonvulsant, pregabalin, vs each monotherapy to treat neuropathic pain due to peripheral neuropathies. In this randomized, double-blind, 3-period crossover trial, participants received oral ALA, pregabalin, and their combination-each for 6 weeks. The primary outcome was mean daily pain intensity at maximal tolerated doses (MTD); secondary outcomes included quality of life (SF-36), sleep (Medical Outcomes Study-Sleep Scale), adverse effects, drug doses, and other measures. Of 55 participants randomized (20-diabetic neuropathy, 19-small fiber neuropathy, and 16-other neuropathies), 46 completed 2 periods, and 44 completed 3. At MTD, the primary outcome of mean pain intensity (0-10) was 5.32 (standard error, SE = 0.18), 3.96 (0.25), 3.25 (0.25), and 3.16 (0.25) at baseline, ALA, pregabalin, and combination, respectively ( P < 0.01 for ALA vs combination and pregabalin). Treatment differences were similar in subgroups with diabetic neuropathy and with other neuropathies. SF-36 total scores (higher number indicates better quality of life) were 66.6 (1.88), 70.1 (1.88), and 69.4 (1.87) with ALA, pregabalin, and combination ( P < 0.05 for ALA vs combination and pregabalin). At MTD, there were no statistically significant treatment differences in adverse effects or drug doses. This trial demonstrates superiority of pregabalin vs ALA but provides no evidence to suggest added benefit of combining ALA with pregabalin to treat neuropathic pain.

Protective effect of pregabalin on renal and renal endothelial damage in sepsis induced by lipopolysaccharide.

OBJECTIVE: We investigated the protective effects of pregabalin (PRG) on kidney and renal endothelial damage in sepsis induced by Lipopolysaccharide (LPS). MATERIALS AND METHODS: Rats were randomly divided into three groups as control, LPS and LPS+PRG. Saline solution was administered 30 mg/kg orally and 5 mg/kg intraperitoneally (i.p.) to the control group. LPS was applied as 5 mg/kg, i.p. to the LPS group. In the LPS+PRG group, PRG at 30 mg/kg orally and one hour before LPS administration, one hour later 5 mg/kg i.p. LPS was applied. Rats were sacrificed 6 hours after LPS administration. RESULTS: White Blood Cell (WBC), granulocyte, Blood Urea Nitrogen (BUN), creatinine, uric asid, Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) significantly increased (p<0.05); platelets (PLT), activated partial thromboplastin time (aPTT) and Total Antioxidant Status (TAS) significantly decreased in the LPS group compared to the control group (p<0.05). In the LPS+PRG group WBC, granulocyte, BUN, creatinine, uric asid, TOS and OSI significantly decreased (p<0.05); PLT, aPTT and TAS significantly increased compared to the LPS group(p<0.05). Histopathological examinations showed that kidney and renal endothelial damage in the LPS group decreased in the LPS+PRG group. Immunohistochemically IL1-ß, IL-6, IL-10, TNF-α expressions in kidney tissue and Toll-Like Receptors-4 (TLR-4) and NF-κB expressions in the renal endothelial tissue significantly increased in the LPS group compared to the control group and significantly decreased in the LPS+PRG group compared to the LPS group (p<0.001). CONCLUSIONS: Sepsis causes kidney and renal endothelial damage and PRG reduces this damage. Therefore PRG can be used in prophylactic treatment in sepsis, supported by more studies.

In this study, kidney and renal endothelial damage in sepsis was investigated. The effect of pregabalin on kidney and renal endothelial damage in sepsis was evaluated.