Pregabalin Research Papers - Academia.edu (original) (raw)

Pregabalin is a new generation antiepileptic that exerts its effect by decreasing the release of such neurotransmitters as glutamate, noradrenaline, and substance P. Pregabalin can be prescribed in Turkey at 150-600 mg to treat neuropathic pain, generalized anxiety disorder, fibromyalgia, and as concomitant therapy in adult patients with partial epilepsy. Experimental studies have shown that pregabalin could be beneficial in the treatment of benzodiazepine dependence and withdrawal, as well as for relapse prevention in patients with alcohol dependence. Nonetheless, the number of case reports on the abuse potential of pregabalin has increased. Herein we present a patient with pregabalin dependence. The patient's underlying alcohol and polysubstance dependence, and symptoms of generalized anxiety were thought to contribute to the development of pregabalin dependence. The patient reported that he had experienced severe withdrawal symptoms when he tried to stop using pregabalin. Bupropion and low-dose quetiapine were added to his paroxetine treatment, and pregabalin was discontinued gradually. Following this treatment the patient had not exhibited any signs of pregabalin dependence for one month. Although pregabalin is a promising drug for various psychiatric disorders, it should be used carefully in patients with a history of substance dependence.

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- Psychology, Complementary and Alternative Medicine, Medicine, Differential Diagnosis

The pharmacokinetic properties of the immediate-release (IR) and the recently developed controlled-release (CR) formulation of pregabalin are dose proportional. Pregabalin IR can be taken with or without food. This analysis characterizes the effect of food on pregabalin CR. The objectives of this analysis were: (1) to evaluate the effect of administration time and fat or caloric content of an accompanying meal on the pharmacokinetic properties of a single dose of pregabalin CR (330 mg) relative to a single dose of pregabalin IR (300 mg); (2) to evaluate the pharmacokinetic properties of a single dose of pregabalin CR administered fasted relative to a single dose of pregabalin CR administered immediately after food; and (3) to determine the safety and tolerability of single-dose administration of pregabalin CR and IR with and without food. The effect of food on the pharmacokinetic properties of pregabalin CR was determined in five phase I, open-label, single-dose, crossover studies (...

- by Tanja Alebic-Kolbah
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- Young Adult, Time Factors, Pregabalin, Biological Availability

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. &

- by Rainer Freynhagen
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- Adolescent, Safety, Constipation, Adverse Events

Statement of the Problem: A prospective, randomized clinical trial (case study) over patients undergoing surgical procedures (40 Pts). All patients chosen for preemptive multimodal analgesia treatment group (40 patients). Methodology & Theoretical Orientation: To give Pregabalin (Lyrica) 75mg 2hrs or more before surgery then 75 mg QHS for 3days postoperative, to be reassessed by APS team if extension needed. No valium with lyrica. To add Celecoxib (if not contraindicated) 200-400mg tablet 1hour before surgery then 200 mg BID for 3 days only. Ranitidine 150mg BID could be added. Surgical site-specific regional analgesia whenever possible. PCA morphine can be used if indicated and as a backup plan for breakthrough pain. Then post.op, Pregabalin, Celecoxib, Solpadeine 2 tablets Q6hrs or TID.
Findings: 30 patients came calm pre-op., smooth for GA, RA blocks, other 10 patients little anxious. All patients examined second day; 30 patients had smooth sleep, no pain after regional blocks, needed PCA morphine 1-5 mg (10 patients). Other 10 patients continued only on oral tablets. Conclusion & Significance: The new preemptive multimodal analgesic combination is safe and effective postoperative, may reduce severity of adverse effects of the opioid. Review; follow up of patients postoperative by APS team for 4 days.

BACKGROUND: Many clinical trials have demonstrated the effectiveness of gabapentin and pregabalin administration in the perioperative period as an adjunct to reduce acute postoperative pain. However, very few clinical trials have examined the use of gabapentin and pregabalin for the prevention of chronic postsurgical pain (CPSP). We (1) systematically reviewed the published literature pertaining to the prevention of CPSP (Ն2 months after surgery) after perioperative administration of gabapentin and pregabalin and (2) performed a meta-analysis using studies that report sufficient data. A search of electronic databases (Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, IPA, and CINAHL) for relevant English-language trials to June 2011 was conducted. METHODS: The following inclusion criteria for identified clinical trials were used for entry into the present systematic review: randomization; double-blind assessments of pain and analgesic use; report of pain using a reliable and valid measure; report of analgesic consumption; and an absence of design flaws, methodological problems or confounders that render interpretation of the results ambiguous. Trials that did not fit the definition of preventive analgesia and did not assess chronic pain at 2 or more months after surgery were excluded. RESULTS: The database search yielded 474 citations. Eleven studies met the inclusion criteria. Of the 11 trials, 8 studied gabapentin, 4 of which (i.e., 50%) found that perioperative administration of gabapentin decreased the incidence of chronic pain more than 2 months after surgery. The 3 trials that used pregabalin demonstrated a significant reduction in the incidence of CPSP, and 2 of the 3 trials also found an improvement in postsurgical patient function. Eight studies were included in a meta-analysis, 6 of the gabapentin trials demonstrated a moderateto-large reduction in the development of CPSP (pooled odds ratio [OR] 0.52; 95% confidence interval [CI], 0.27 to 0.98; P ϭ 0.04), and the 2 pregabalin trials found a very large reduction in the development of CPSP (pooled OR 0.09; 95% CI, 0.02 to 0.79; P ϭ 0.007). CONCLUSIONS: The present review supports the view that perioperative administration of gabapentin and pregabalin are effective in reducing the incidence of CPSP. Better-designed and appropriately powered clinical trials are needed to confirm these early findings.

- by Hance Clarke and +1
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- Evidence Based Medicine, Chronic Pain, Treatment Outcome, Adolescent

Pregabalin (148553-50-8) is a drug that is mostly sold under the brand name Lyrica in various regions in the world. It is used to treat pain caused by nerve damage due to diabetes or to shingles (herpes zoster) infection. It may also be used to treat nerve pain caused by spinal cord injury. This medication is also used to treat pain in people with fibromyalgia.Pregabalin is also used with other medications to treat certain types of seizures (partial onset seizures).

- by AAS RAW
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- Lifestyle, Pregabalin

Post herpetic neuralgia is a most common complication of herpes zoster which is difficult to treat. Significant beneficial effects found when treated with antiviral, tricyclic antidepressant, anticonvulsive like gabapentine and pregabalin, opioid and non opioid analgesic etc. Primary prevention can also be done with vaccine. The aim of this randomized comparative study was to establish clinical efficacy with amitriptyline and pregabalin.

- by Samiran Bisai
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- Clinical Trial, Herpes Zoster, Pregabalin

- by Marina Englesakis and +1
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- Chronic Pain, Systematic Reviews, Pregabalin, Gabapentin

Pregabalin is a new generation antiepileptic that exerts its effects through decreasing the release of neurotransmitters such as glutamate, noradrenaline, and substance P. It is a gamma-aminobutyricacid (GABA) analogue utilized in the treatment of neuropathic pain and generalized anxiety disorder in addition to epilepsy. There are studies conducted in recent years showing that it is effective in the treatment of benzodiazepine and alcohol dependence. However, cases in which pregabalin dependence has developed have also been reported. As such, pregabalin should be used carefully. This article presents a case report of a 27-year-old man who abused pregabalin, and had withdrawal symptoms, after starting to take pregabalin to stop taking synthetic marijuana (Jamaica). The patient had been taking 2100 mg/day of pregabalin, and stated that he had withdrawal symptoms which included irritability, shaking, heartburn, inertia, depression, and an inability to work. The daily dose of pregabalin was decreased, and a chart was introduced to help him. He was started on paroxetine 20 mg/day, and quetiapine XR 50 mg/day. After this intervention, the patient managed to quit pregabaline in 60 days.

- by Gülay Oğuz and +1
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- Psychiatry, Psychopharmacology, Substance Misuse, Substance Abuse Treatment

Резюме. Прегабалин является новым анксиолитиком, механизм действия которого связан со снижением повышенного выброса возбуждающих нейромедиаторов, в том числе глутамата. Вместе с тем нарушения глутаматергической нейро-трансмиссии в настоящее время рассматриваются в качестве основного патогенетического механизма шизофрении. Эти данные наряду с тем, что феномен тревоги занимает видное место в клинической картине формирующихся психозов, поз-волили сформулировать гипотезу о перспективности применения при них прегабалина в комбинации с антипсихотика-ми. В качестве иллюстрации приведен доклад о серии случаев успешного усиления прегабалином стабильной антипсихо-тической терапии на ранних этапах экзацербаций шизофренического процесса. Ключевые слова: прегабалин, атипичные антипсихотики, шизофрения. Summary. Pregabalin is the novel anxiolytic drug which mechanism of action associated with normalization of increased release of exciting neuromediators including glutamate. At the same time disturbances of glutamatergic neurotransmission nowadays are thought as the major pathogenetic mechanism of schizophrenia. These considerations along with that anxiety phenomenon is prominent in the clinical picture of early phases of psychotic exacerbations allowed to hypothesize the effectiveness of combination of antipsychotics with pregabalin in the treatment of such states. This hypothesis is illustrated by report of a case series of successful augmentation of stable antipsychotic treatment with pregabalin in the treatment of early stages of schizophrenic exacerbations.

- by Timur Syunyakov and +1
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- Schizophrenia, Acute Psychosis, Antipsychotics, Pregabalin

SUMMARY The most common complication of herpes zoster in immunocompetent
patients is postherpetic neuralgia, which is very diﬃcult to treat. Signiﬁcant
beneﬁcial eﬀects have been found for amitriptyline, gabapentin, pregabalin,
carbamazepine, sodium valproate, oxycodone, corticosteroid, topical capsaicin,
tramadol, etc. The aim of this open randomized comparative study was to demonstrate
clinical eﬃcacy of amitriptyline and pregabalin. The study included 50
patients, 32 (64%) male and 18 (36%) female, randomized to receive either amitriptyline
or pregabalin (n=25 each). Amitriptyline was administered in a dose of
25 mg once daily and pregabalin in a dose of 75 mg twice daily. Inclusion criteria
were as follows: postherpetic neuralgia of more than 1 month duration; pain of
at least moderate severity; and patient age 40 years or older and no pregnancy.
Patients with a history of any serious diseases (renal, cardiac, hepatic or seizure)
were excluded. Total treatment period spanned 8 weeks, with patient follow up
visits at 2, 4 and 8 weeks to assess the degree of improvement in pain perception
and any adverse reaction. Patients with four herpes zoster types were included in
this study, of which thoracic type predominated (54%). Other types were cervical
in 12 (24%), trigeminal in 8 (16%) and lumbosacral in 3 (6%) patients. Prodromal
symptoms before herpes zoster were reported by 66% of study patients. Satisfactory
improvements of pain perception at the end of 8 weeks (>75%) were noticed
in pregabalin group, which was statistically signiﬁcant (χ2=10.08; P<0.05).
Dry mouth was the commonest complication in amitriptyline group and dizziness
in pregabalin group. More importantly, none of the patients stopped treatment
due to adverse reaction. In conclusion, therapy with pregabalin is better
compared to amitriptyline in postherpetic neuralgia patients. However, a similar
study in a larger sample is required to validate the present ﬁndings.

- by Samiran Bisai
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- Clinical Trials, Dermatology, Pregabalin, Postherpetic Neuralgia

Pregabalin is a medication that can decrease neuronal hyperexcitability, relieve neuropathic pain, and reach stable plasma levels after a titration period of only a few days.Its use during oxaliplatin infusions was not able to decrease the incidence of chronic, oxalipaltin-related neuropathic pain, compared with placebo. Patients with colorectal cancer (CRC) receiving oxaliplatin (OXA) develop acute and chronic painful oxaliplatin-induced peripheral neuropathy (OXAIPN). Acute and chronic OXA-related neuropathies have different pathophysiological bases, but both lead to a common phenomenon: central sensitization (CS) of nociceptive neuronal networks, leading to increased sensitivity (hyperlgesia, allodynia) in the somatosensory system, the common ground of chronic neuropathic pain. Because CS is related to increased risk of painful OXAIPN, we hypothesized that preemptive use of the anti-hyperalgesic drug pregabaline (known to decrease CS) during OXA infusions would decrease the incid...

- by Mario Brotto
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- Pain, Pregabalin

Editor's key points † Meta-analysis of perioperative pregabalin and postoperative analgesia identified 11 studies. † Pregabalin produced a dose-related reduction in postoperative opioid use. † Pregabalin reduced postoperative nausea and vomiting, but the incidence of visual disturbance was increased. † The diverse nature of the surgery and anaesthetic techniques included suggest that large randomized, controlled trials are still needed.

- by Ho Yuen
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- Postoperative Pain Management and Measurement, Pregabalin

Background: Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by patients. The optimal treatments for uremic pruritus are not well defined. Study Design: Systematic review. Setting & Population: Adult patients with advanced CKD (stage $ 3) or receiving any form of dialysis. Selection Criteria for Studies: PubMed, CINAHL, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and ClinicalTrials.gov from their inception to March 6, 2017, were systematically searched for randomized controlled trials (RCTs) of uremic pruritus treatments in patients with advanced CKD (stage $ 3) or receiving any form of dialysis. 2 reviewers extracted data independently. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. Intervention: Any intervention for the treatment of uremic pruritus was included. Outcomes: A quantitative change in pruritus intensity on a visual analogue, verbal rating, or numerical rating scale. Results: 44 RCTs examining 39 different treatments were included in the review. These treatments included gabapentin, pregabalin, mast cell stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments. The largest body of evidence was found for the effectiveness of gabapentin. Due to the limited number of trials for the other treatments included, we are unable to comment on their efficacy. Risk of bias in most studies was high. Limitations: Heterogeneity in design, treatments, and outcome measures rendered comparisons difficult and precluded meta-analysis. Conclusions: Despite the acknowledged importance of uremic pruritus to patients, with the exception of gabapentin, the current evidence for treatments is weak. Large, simple, rigorous, multiarm RCTs of promising therapies are urgently needed.

- by Claudio Rigatto
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- Medicine, Phototherapy, Amines, Capsaicin

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.

- by Francesco D'Amico and +2
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- Immunology, Quality of life, Treatment Outcome, Fibromyalgia

Background: Synedrella nodiflora is used by traditional healers in Ghana for the management of epilepsy and pain. The hydro-ethanolic extract of the whole plant has demonstrated antinociceptive effect in various animal models of pain. This study investigated the potential benefit of the hydro-ethanolic extract in a rat model of paclitaxel-induced neuropathic pain. Methods: Neuropathy was induced in rats by a continuous intraperitoneal administration of paclitaxel (2 mg/kg) for 5 days. Baseline latencies to thermal pain were recorded before the first injection of paclitaxel and during the 5 day induction period. Following the induction, the rats in designated treatment group were treated with the hydro-ethanolic extract (100, 300 and 1000 mg/kg, p.o) or pregabalin (10, 30 and 100 mg/kg) or vehicle (distilled water) and their responses to thermal hyperalgesia measured every 30 for a total period of 3 h. Results: There was a significant difference between the baseline reaction latency and what was observed on the 5th day of the induction of neuropathy. Two days after the induction of neuropathy, the extract and pregabalin significantly and dose-dependently produced antinociceptive effect during the 3-h test period. Conclusion: The hydro-ethanolic extract of the whole plant of Synedrella nodiflora possess analgesic effect in paclitaxel-induced neuropathy in rats.

- by Patrick Amoateng (PhD)
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- Pharmacology, Medicine, Neuropathic pain, Ethanol

More patient-specific medical care is expected as more is learned about variations in patient responses to medical treatments. Analytical tools enable insights by linking treatment responses from different types of studies, such as randomized controlled trials (RCTs) and observational studies. Given the importance of evidence from both types of studies, our goal was to integrate these types of data into a single predictive platform to help predict response to pregabalin in individual patients with painful diabetic peripheral neuropathy (pDPN). We utilized three pivotal RCTs of pregabalin (398 North American patients) and the largest observational study of pregabalin (3159 German patients). We implemented a hierarchical cluster analysis to identify patient clusters in the Observational Study to which RCT patients could be matched using the coarsened exact matching (CEM) technique, thereby creating a matched dataset. We then developed autoregressive moving average models (ARMAXs) to e...

- by Roger Edwards
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- Medicine, Cluster Analysis, Aged, Public health systems and services research

Pregabalin is an antagonist of voltage gated Ca 2+ channels and specifically binds to alpha-2-delta subunit to produce antiepileptic and analgesic actions. It successfully alleviates the symptoms of various types of neuropathic pain and presents itself as a first line therapeutic agent with remarkable safety and efficacy. Preclinical studies in various animal models of neuropathic pain have shown its effectiveness in treating the symptoms like allodynia and hyperalgesia. Clinical studies in different age groups and in different types of neuropathic pain (peripheral diabetic neuropathy, fibromyalgia, post-herpetic neuralgia, cancer chemotherapy-induced neuropathic pain) have projected it as the most effective agent either as monotherapy or in combined regimens in terms of cost effectiveness, tolerability and overall improvement in neuropathic pain states. Preclinical studies employing pregabalin in different neuropathic pain models have explored various molecular targets and the signaling systems including Ca 2+ channel-mediated neurotransmitter release, activation of excitatory amino acid transporters (EAATs), potassium channels and inhibition of pathways involving inflammatory mediators. The present review summarizes the important aspects of pregabalin as analgesic in preclinical and clinical studies as well as focuses on the possible mechanisms.

- by nirmal singh
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- Medicine, Neuropathic pain, Diabetic Neuropathy, Current Neuropharmacology
- by Eleftheria KARAMPLI
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- Bioinformatics, Cognitive Science, Life Sciences, Medicine

Prediction of final clinical outcomes based on early weeks of treatment can enable more effective patient care for chronic pain. Our goal was to predict, with at least 90% accuracy, 12- to 13-week outcomes for pregabalin-treated painful diabetic peripheral neuropathy (pDPN) patients based on 4 weeks of pain and pain-related sleep interference data. We utilized active treatment data from six placebo-controlled randomized controlled trials (n = 939) designed to evaluate efficacy of pregabalin for reducing pain in patients with pDPN. We implemented a three-step, trajectory-focused analytics approach based upon patient responses collected during the first 4 weeks using monotonicity, path length, frequency domain (FD), and k-nearest neighbor (kNN) methods. The first two steps were based on combinations of baseline pain, pain at 4 weeks, weekly monotonicity and path length during the first 4 weeks, and assignment of patients to one of four responder groups (based on presence/absence of 50...

- by Roger Edwards
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- Medicine, Therapy, Pregabalin, Pharmacology and pharmaceutical sciences

Radon inhalation brings pain relief for chronic constriction injury- (CCI-) induced neuropathic pain in mice due to the activation of antioxidative functions, which is different from the mechanism of the pregabalin effect. In this study, we assessed whether a combination of radon inhalation and pregabalin administration is more effective against neuropathic pain than radon or pregabalin only. Mice were treated with inhaled radon at a concentration of 1,000 Bq/m(3) for 24 hours and pregabalin administration after CCI surgery. In mice treated with pregabalin at a dose of 3 mg/kg weight, the 50% paw withdrawal threshold of mice treated with pregabalin or radon and pregabalin was significantly increased, suggesting pain relief. The therapeutic effects of radon inhalation or the combined effects of radon and pregabalin (3 mg/kg weight) were almost equivalent to treatment with pregabalin at a dose of 1.4 mg/kg weight or 4.1 mg/kg weight, respectively. Radon inhalation and the combination ...

- by Takahiro Kataoka
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- Antioxidants, Radon, Pregabalin, Constriction

The aim of this study was to analyze the cost utility of a group-based form of acceptance and commitment therapy (GACT) in patients with fibromyalgia (FM) compared with patients receiving recommended pharmacological treatment (RPT) or on a waiting list (WL). The data were derived from a previously published study, a randomized controlled trial that focused on clinical outcomes. Health economic outcomes included health-related quality of life and health care use at baseline and at 6-month follow-up using the EuroQoL and the Client Service Receipt Inventory, respectively. Analyses included quality-adjusted life years, direct and indirect cost differences, and incremental cost effectiveness ratios. A total of 156 FM patients were randomized (51 GACT, 52 RPT, 53 WL). GACT was related to significantly less direct costs over the 6-month study period compared with both control arms (GACT €824.2 ± 1,062.7 vs RPT €1,730.7 ± 1,656.8 vs WL €2,462.7 ± 2,822.0). Lower direct costs for GACT compa...

- by Antoni Serrano-Blanco
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- Group Psychotherapy, Acceptance and Commitment Therapy, Spain, Fibromyalgia

Aim/Introduction: Acute ischemia reperfusion (IR) injury observed in the lower extremities occurs especially when a temporary cross-clamp is applied to the abdominal aorta during aortic surgery. Preoperative pregabalin has been used as a part of multimodal analgesia in postoperative pain treatment in recent years. Pregabalin has become one of the increasingly common agents in postoperative analgesia. In this study, we aimed to investigate the effect of pregabalin on erythrocyte deformability in rats undergoing IR.
Materials and Methods: 24 male Wistar albino rats weighing between 200-250 g were used in the study. Rats were randomly divided into 4 groups of 6 rats each (Control, Ischemia-Reperfusion (IR), IR-Pregabalin 50 mg (50 mg.kg-1), IRPregabalin 200 mg (200 mg.kg-1). Pregabalin was administered intraperitoneally 30 min before the procedure. An atraumatic microvascular clamp was placed across the infrarenal abdominal aorta in the IR groups. Following 120 min of ischemia,
the clamp was removed and reperfusion was continued for 120 min. All rats were euthanized by intraperitoneal administration of ketamine (100 mg•kg−1) and taking blood from the abdominal aorta. Erythrocytes were seperated from heparinized whole blood samples. Deformability measurements were made in erythrocyte suspensions in phosphate buffered saline. A constant flow filtrometer system was used to measure erythrocyte deformability and relative resistance was calculated.
Results: It was found that the formation of ischemia reperfusion increases the relative resistance according to the control group (p < 0.0001). It was determined that application of pregabalin 50 or 200 mg did not change erythrocyte deformability in ischemia reperfusion-induced rats (p = 0.632, p = 0.811).
Conclusion: The administration of 50 or 200 mg of pregabalin has no negative effect on the erythrocyte deformability in ischemia reperfusion-induced rats. We think that pregabalin can be safely used for analgesia in the cases of IR. However, these findings should be supported by clinical and experimental studies carried out in more detailed and broader series.

Discontinuation effects following cessation of 12 and 24 wk of pregabalin treatment for generalized anxiety disorder (GAD) were evaluated in a placebo-and lorazepam-controlled, randomized, double-blind, multicentre trial conducted in 16 countries. The study design consisted of two 12-wk treatment periods (periods 1 and 2), each followed by a 1-wk taper and two post-discontinuation assessments, one immediately following the taper and one 1-wk post-taper. Patients were assigned to receive an initially flexible dose of pregabalin 450-600 mg/d, pregabalin 150-300 mg/d, or lorazepam 3-4 mg/d for 6 wk; responders continued fixed-dose therapy for 6 additional weeks. Patients entering period 2 continued on the same fixed dose or switched to placebo. Discontinuation effects were evaluated with the Physician Withdrawal Checklist (PWC) and reported discontinuation-emergent signs and symptoms. Rebound anxiety was measured with the Hamilton Anxiety Rating Scale. GAD symptoms improved with all treatments and improvements were maintained over 12 and 24 wk. Low levels of discontinuation symptoms were evident in all treatment groups. For patients who received active treatment during both periods, mean (95% confidence interval) increases on the PWC from last visit on active treatment to the second post-discontinuation assessment were: pregabalin 450-600 mg/d: 2.8 (1.6-3.9), pregabalin 150-300 mg/d: 1.7 (0.7-2.8), lorazepam 3-4 mg/d: 2.2 (1.0-3.5). Rates of rebound anxiety were also low at both 12 and 24 wk (0-6%). This suggests that risk of discontinuation symptoms and rebound anxiety are low for pregabalin after 12 and 24 wk of treatment.

- by Celso Iglesias
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- Anxiety Disorders, Neuropsychopharmacology, Adolescent, Medicine

A facile, rapid, and highly sensitive microchip-based electrokinetic chromatographic method was developed for the simultaneous analysis of two gabapentinoid drugs, gabapentin (GPN) and pregabalin (PGN). Both drugs were first reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) via nucleophilic substitution reactions to yield highly fluorescent products with λex/em 470/540nm. Analyses of both fluorescently labeled compounds were achieved within 200s in a poly(methyl methacrylate) (PMMA) microchip with a 30mm separation channel. Optimum separation was achieved using a borate buffer (pH 9.0) solution containing methylcellulose and β-cyclodextrin (β-CD) as buffer additives. Methylcellulose acted as a dynamic coating to prevent adsorption of the studied compounds on the inner surfaces of the microchannels, while β-CD acted as a pseudo-stationary phase to improve the separation efficiency between the labeled drugs with high resolution (Rs>7). The fluorescence intensities of the l...

- by Jenny Jeehan Nasr
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- Engineering, Chemistry, Technology, Chromatography

Pregabalin (Lyrica(®)) is approved as an immediate-release (IR) formulation for administration twice (BID) or three times (TID) a day depending on indication. Once daily (QD) dosing may be appropriate for ease of clinical use and patient convenience. The objectives of this analysis were: (1) to evaluate the pharmacokinetics of pregabalin controlled-release (CR) administered with food relative to the pregabalin IR formulation administered fasted; (2) to evaluate the pharmacokinetics of a two-tablet dose of pregabalin CR compared with the equivalent one-tablet dose of pregabalin CR; and (3) to determine the safety and tolerability of multiple-dose administration of pregabalin CR and IR. The pharmacokinetic properties of pregabalin CR were determined in four phase I, open-label, multiple-dose crossover studies (18-24 participants/study). Pregabalin CR (82.5, 165, 330 or 660 mg/day) administered QD was compared with pregabalin IR (75, 150, 300 or 600 mg/day, respectively) administered e...

- by Tanja Alebic-Kolbah
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- Food, Young Adult, Tablets, Pregabalin

Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcu...

- by Lawrence Gibbs
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- Amines, Tramadol, Capsaicin, Phenols

- by Karine Ferreira
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- Pain, Pregabalin

AIm: To evaluate the effect of pregabalin pre-treatment on spinal cord ischemia-reperfusion (I/R) injury and compare with methylprednisolone (MP). mATERIAl and mEThODS: Thirty-two rats were randomly divided into four groups as follow: Group 1 (sham)(n=8), group 2 (ischemia only)(n=8), group 3 (30 mg/kg pregabalin)(n=8), and group 4 (30 mg/kg methylprednisolone)(n=8). Laparotomy was performed without aortic clamp in the sham group. All animals were sacrificed 24 hours after surgery. The spinal cord tissue samples were harvested and caspase-3 activity, tumor necrosis factor-alpha (TNF-α) and Interleukin-1 Beta (IL-1β) levels, catalase (CAT) activity, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) levels malondialdehyde (MDA) levels and nitric oxide (NO) levels were analyzed to investigate the effects of different excitatory and inflammatory pathways in mechanism of I/R injury. Ultrastructural and histopathological examinations were carried out. Neurological recovery was measured by Basso, Beattie, Bresnahan (BBB) test and Inclined Plane Test. RESUlTS: Decresead caspase-3 activity and decreased inflammatory markers like TNF-α, IL-1β, and decresaed excitotatory pathways like CAT, GPx, MDA, NO and SOD were observed in both pregabalin pre-treatment and MP treatment groups. Pregabalin pre-treatment produced better ultrastructural results compared to MP treatment, as with histopathological examination. Pregabalin group showed better recovery compared to MP treament group according to BBB scoring system. CONClUSION: Pregabalin pre-treatmet and MP treatment both has neuroprotective effect on I/R injury by decreasing caspase dependant apoptosis, and inflammatory and oxidative stress markers. In addition, pregabalin pre-treatment had better clinical effects compared to MP treatment.

- by emre cemal Gokce
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- Oxidative Stress, Apoptosis, Rats, Reperfusion injury

- by Toni Serrano Blanco
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- Group Psychotherapy, Acceptance and Commitment Therapy, Spain, Fibromyalgia

Please cite this article in press as: Srivastava VK, et al. Prophylactic use of pregabalin for prevention of succinylcholineinduced fasciculation and myalgia: a randomized, double-blinded, placebo-controlled study. Rev Bras Anestesiol.... more

- by ABHISHEK Mishra
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- Spine, Prospective studies, Young Adult, Incidence

Pregabalin, a synthetic derivate of the inhibitory neurotransmitter
γ-aminobutyric acid, shows antiepileptic, analgesic,
anticonvulsant, anxiolytic, and sleep-modulating
activities. The major advantage of pregabalin is its relative
reliability, easy use, high tolerance, and lack of negative
interaction with other drugs. A 65-year-old woman with
medical histories of diabetes mellitus, lumbar spondylosis,
diabetic nephropathy, chronic renal failure, and anemia of
chronic disease was admitted with the complaint of dizziness
and syncope. She had been taking pregabalin 300 mg daily
for 8 months. Electrocardiogram revealed complete atrioventricular
(AV) block and right bundle-brunch block with a
heart rate of 39 per minute. Her creatinine was 1.8 mg/dL,
and creatinine clearance was 50 mL/min. Pregabalin
treatment was discontinued. Four days later, the complete
AV block resolved spontaneously to Mobitz type II block
and to sinus rhythm with right bundle-brunch block on the
seventh day. To our knowledge, this is the first case of
complete AV block associated with pregabalin. We believe
that AV block occurred as a result of pregabalin's effect on
L-type Ca++ channels in the heart. Pregabalin's different
effects on electrocardiogram and on the heart in different
individuals may have an association with the patterns of
distribution of the L-type calcium channels in myocardium.

- by Mucahit Emet
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- Cardiology, Emergency Medicine, Side Effects, Heart Disease

The combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration. This retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of ove...

- by Rabia Atayee
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- Pain, Patient Safety, Medicine, Pain Management

Introduction: Neuropathic pain is the pain that arises as a direct consequence of a lesion or disease affecting the somatosensory system. It could be central (postraumatic pain, multiple sclerosis, pain due to spinal cord injury, pain related to acquired immune deficiency syndrome, AIDS) or peripheral (post-herpetic neuralgia or diabetic peripheral neuropathy). Classical analgesic drugs have failed to show good efficacy for the treatment of neuropathic pain. For that reason, antiepileptic drugs such as pregabalin have been introduced for the treatment of this pain. Over the last years, pregabalin has been used to relieve neuropathic pain due to all causes leading to its over prescription. Objective: The aim of this research was to analyse the efficacy of pregabalin for the treatment of different types of neuropathic pain. Methodology: Randomized placebo controlled clinical trials were analysed following systematic methodological procedure. Results: In clinical trials that include pa...

- by Aitziber Mendiguren
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- Medicine, Pregabalin

Background: L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results: A seven-day treatment with L-acetylcarnitine (100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain. L-Acetylcarnitine-induced analgesia persisted for at least 14 days after drug withdrawal. In contrast, the analgesic effect of pregabalin, amitryptiline, ceftriaxone, and N-acetylcysteine disappeared seven days after drug withdrawal. L-acetylcarnitine treatment enhanced mGlu2/3 receptor protein levels in the dorsal region of the spinal cord. This effect also persisted for two weeks after drug withdrawal and was associated with increased levels of acetylated histone H3 bound to the Grm2 gene promoter in the dorsal root ganglia. A long-lasting analgesic effect of L-acetylcarnitine was also observed in mice subjected to chronic constriction injury of the sciatic nerve. In these animals, a 14-day treatment with pregabalin, amitryptiline, tramadol, or L-acetylcarnitine produced a significant antiallodynic effect, with pregabalin displaying the greatest efficacy. In mice treated with pregabalin, tramadol or L-acetylcarnitine the analgesic effect was still visible 15 days after the end of drug treatment. However, only in mice treated with L-acetylcarnitine analgesia persisted 37 days after drug withdrawal. This effect was associated with an increase in mGlu2/3 receptor protein levels in the dorsal horns of the spinal cord. Conclusions: Our findings suggest that L-acetylcarnitine has the unique property to cause a long-lasting analgesic effect that might reduce relapses in patients suffering from chronic pain.

- by Matteo Bernabucci
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- Inflammation, Medicine, Pain Management, Neuropathic pain

- by Lawrence Gibbs
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- Medicine, Amines, Tramadol, Capsaicin

Objective;-Pregabalin (PGB) is an α2β calcium channel subunit ligand that has previously been shown to reduce chronic pain in multiple conditions. Preclinical studies indicate that PGB may down-regulate brain glutamate release while also inhibiting astrocyte induction of glutamatergic synapse formation. Recent clinical research supports PGB modulating glutamatergic activity and functional brain connectivity in order to produce analgesia. However, no studies have examined concurrent changes in brain gray matter volume (GMV) or evoked-pain connectivity in humans receiving PGB. Methods-Sixteen female fibromyalgia patients completed a randomized double-blind twoperiod cross-over study of PGB versus placebo (PBO). Before and after each period, patients had high-resolution structural and evoked pressure-pain functional brain imaging. GMV was analyzed using voxel-based morphometry, and functional connectivity during evoked pressure-pain was also assessed. Results-PGB administration significantly reduced GMV within the posterior insula bilaterally, whereas there were no significant changes in insular GMV following PBO treatment. GMV reductions were also observed when comparing PGB versus PBO treatment in the medial frontal gyrus, which were associated with reduced clinical pain. These reductions in insular GMV were associated with concomitant reductions in connectivity to the default mode network (DMN), which was also associated with reduced clinical pain.

- by Daniel Clauw
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- Chronic Pain, Fibromyalgia, Pregabalin, Cross-Over Studies

Solid state studies of C-butyl-resorcin[4]arene with pregabalin (Lyrica, Nervalin) in nitrobenzene yielded a cocrystal of C-butyl-resorcin[4]arene with 4-isobutylpyrrolidone-2. A combined experimental and quantum chemical investigation... more

Background: Anxiety disorders are among the most common psychiatric illnesses, with generalized anxiety disorder (GAD) being one of the most common. Sleep disturbances are highly prevalent in GAD patients. While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials, mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin. Thus, the objective of this study was to model the longitudinal latent effect of pregabalin or usual care (UC) therapies on changes in sleep in outpatients with GAD under routine clinical practice. Methods: Male and female GAD outpatients, aged 18 years or above, from a 6-month prospective noninterventional trial were analyzed. Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms (assessed with Hamilton Anxiety Scale) and sleep disturbances (assessed with Medical Outcomes Study-Sleep Scale [MOS-S]) were estimated by a conditional latent curve model applying structural equation modeling. Results: A total of 1,546 pregabalin-naïve patients were analyzed, 984 receiving pregabalin and 562 UC. Both symptoms of anxiety and sleep disturbances were significantly improved in both groups, with higher mean (95% confidence interval) score reductions in subjects receiving pregabalin:-15.9 (-15.2;-16.6) vs-14.5 (-13.5;-15.5), P=0.027, in Hamilton Anxiety Scale; and-29.7 (-28.1;-31.3) vs-24.0 (-21.6;-26.4), P0.001, in MOSS. The conditional latent curve model showed that the pregabalin effect on sleep disturbances was significant (γ =-3.99, P0.001), after discounting the effect on reduction in anxiety symptoms. A mediation model showed that 70% of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement. Conclusion: A substantial proportion of the incremental improvements in anxiety-related sleep disturbances with pregabalin vs UC were explained by its direct effect, not mediated by improvements in anxiety symptoms.

- by Jose Olivares
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- Anxiety Disorders, Treatment Outcome, Prospective studies, Longitudinal Studies

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.... more

- by Javier García Campayo
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- Immunology, Quality of life, Treatment Outcome, Fibromyalgia

- by alberto mello
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- Pain, Pregabalin

The Brugada electrocardiogram pattern is characterized by coved-type ST-elevation... more

The Brugada electrocardiogram pattern is characterized by coved-type ST-elevation (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2 mm) in the right precordial leads. We report the case of a 62-year-old man, with bipolar disorder, admitted to the emergency department because of dyspnea and chest discomfort. The patient was on treatment with pregabalin and quetiapine. Unexpectedly, electrocardiogram at admission showed diffuse ST-elevation, more evident in inferior leads, where a Brugada-like pattern was present. The patient underwent coronary angiography with a diagnosis of suspected acute coronary syndrome. Coronary angiography, however, showed mild coronary artery disease not requiring coronary angioplasty. Echocardiography did not reveal left ventricular dysfunction or pericardial effusion. Troponin levels remained normal over serial controls. Eventually, chest radiography showed lung opacities and consolidation suggestive for pneumonia. To the best of our knowledge, this is one of the first cases showing a transient Brugada-like electrocardiogram pattern in inferior leads, probably amplified by the administration of pregabalin and quetiapine.

- by Antonio Gaglione
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- Bipolar Disorder, Electrocardiography, Echocardiography, Coronary Angiography

The first two alpha2delta ligands - gabapentin (GBP) and pregabalin (PGB) - were initially synthesized as antiepileptics; however, they were later also found to be useful for the treatment of additional conditions. Relevant publications describing potential underlying mechanisms, clinical pharmacokinetics/pharmacokinetics, and clinical efficacy and safety of these drugs in various disease conditions were searched in PubMed and Scopus and included in this review. Expert commentary: GBP and PGB are effective for the treatment neuropathic pain, fibromyalgia and epilepsy; in addition, they may be useful for the reduction of postoperative pain. PGB is also effective for the treatment of generalized anxiety disorder and GBP for the treatment of restless legs syndrome. GBP may be considered a treatment option for pain associated with Guillain-Barré Syndrome and phantom limb and for the management of uremic pruritus. Mirogabalin (MGB), recently developed, is being investigated for the treatment of peripheral neuropathic pain and fibromyalgia, showing promising results in patients with diabetic peripheral neuropathy. Their most frequent adverse reactions are of neuropsychiatric nature and include fatigue, dizziness, sedation, somnolence, and ataxia; peripheral edema and weight gain are also frequently described. Pharmacokinetic interactions are scarce; however, pharmacodynamic interactions have been described in association with drugs with CNS-depressant effects.

- by Elena Calandre
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- Amines, Pregabalin, Ligands, Neurosciences

Background: Anticipating and controlling drug-drug interactions (DDIs) in older patients with painful diabetic peripheral neuropaty (pDPN) presents a significant challenge to providers. The purpose of this study was to examine the impact of newly initiated pregabalin or duloxetine treatment on Medicare Advantage Prescription Drug (MAPD) plan pDPN patients' encounters with potential drug-drug interactions, the healthcare cost and utilization consequences of those interactions, and opioid utilization. Methods: Study subjects required a pregabalin or duloxetine pharmacy claim between 07/01/2008-06/30/2012 (index event), ≥1 inpatient or ≥2 outpatient medical claims with pDPN diagnosis between 01/01/2008-12/31/ 2012, and ≥12 months pre-and ≥6 post-index enrollment. Propensity score matching was used to balance the pregabalin and duloxetine cohorts on pre-index demographics and comorbidities. Potential DDIs were defined by Micromedex 2.0 and identified by prescription claims. Six-month post-index healthcare utilization (HCU) and costs were calculated using pharmacy and medical claims. Results: No significant differences in pre-index demographics or comorbidities were found between pregabalin subjects (n = 446) and duloxetine subjects (n = 446). Potential DDI prevalence was significantly greater (p < 0.0001) among duoxetine subjects (56.7%) than among pregabalin subjects (2.9%). There were no significant differences in HCU or costs between pregablin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($13,908 vs. $9,830; p = 0.001), more subjects with ≥1 inpatient visits (35.6% vs 25.4%; p = 0.02), and more subjects with ≥1 emergency room visits (32.8% vs. 20.7%; p = 0.005) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a difference between pregabalin and duloxetine subjects in their respective pre-versus-post differences in milligrams (mg) of morphine equivalents/ 30 days used (60.2 mg and 176.9 mg, respectively; p = 0.058). Conclusion: The significantly higher prevalence of potential DDIs and potential cost impact found in pDPN duloxetine users, relative to pregabalin users, underscore the importance of considering DDIs when selecting a treatment.

- by Joseph Cappelleri
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- Pain, Drug interactions, Adolescent, Library and Information Studies

Diabetic neuropathy is the most common complication of diabetes mellitus, and the different drug combinations available do not provide effective pain relief. The present study was performed to observe the effect of amitripyline, duloxetine, sitagliptin, and pregabalin, and their combinations on streptozotocin (STZ)-induced diabetic neuropathy. Diabetic neuropathy was induced by STZ, and the tail-flick test was used to assess thermal hyperalgesia before and after (at 30, 60, and 120 min) drug administration. One week after STZ administration, the blood glucose level was observed to be in the diabetic range. Administration of all the drugs except sitagliptin increased the tail-flick latency significantly as compared to control. Further, the drugs amitriptyline, duloxetine, and pregabalin showed significant pain-relieving effect, when either two of them were administered in combination, although the different combinations had varied degree of pain relief. However, sitagliptin was obser...

- by Amol Yadav
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- Rats, Wistar Rats, Combination drug therapy, Pregabalin

Background:Diabetic neuropathy is the most common complication of diabetes mellitus, and the different drug combinations available do not provide effective pain relief. The present study was performed to observe the effect of amitripyline, duloxetine, sitagliptin, and pregabalin, and their combinations on streptozotocin (STZ)-induced diabetic neuropathy.Methods:Diabetic neuropathy was induced by STZ, and the tail-flick test was used to assess thermal hyperalgesia before and after (at 30, 60, and 120 min) drug administration. One week after STZ administration, the blood glucose level was observed to be in the diabetic range.Results:Administration of all the drugs except sitagliptin increased the tail-flick latency significantly as compared to control. Further, the drugs amitriptyline, duloxetine, and pregabalin showed significant pain-relieving effect, when either two of them were administered in combination, although the different combinations had varied degree of pain relief. Howev...

- by Amol Yadav
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- Rats, Wistar Rats, Combination drug therapy, Pregabalin

- by Camila Dale
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- Pain, Pregabalin

- by Mick Serpell
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- Adolescent, Safety, Constipation, Adverse Events

- by Alberto Savoldelli
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- Cluster Analysis, Aged, Public health systems and services research, Prognosis