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The Cochrane Database of Systematic... Mar 2022This is an updated version of the Cochrane Review last published in Issue 7, 2019; it includes two additional studies. Epilepsy is a common neurological disease that... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review last published in Issue 7, 2019; it includes two additional studies. Epilepsy is a common neurological disease that affects approximately 1% of the UK population. Approximately one-third of these people continue to have seizures despite drug treatment. Pregabalin is one of the newer antiepileptic drugs that has been developed to improve outcomes. In this review we summarised the current evidence regarding pregabalin when used as an add-on treatment for drug-resistant focal epilepsy.
OBJECTIVES
To assess the efficacy and tolerability of pregabalin when used as an add-on treatment for drug-resistant focal epilepsy.
SEARCH METHODS
For the latest update we searched the following databases on 16 November 2020: Cochrane Register of Studies (CRS Web), and MEDLINE (Ovid, 1946 to 16 November 2020). CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organisation International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups, including Epilepsy. We imposed no language restrictions. We contacted the manufacturers of pregabalin and authors in the field to identify any relevant unpublished studies.
SELECTION CRITERIA
We included randomised controlled trials comparing pregabalin with placebo or an alternative antiepileptic drug as an add-on for people of any age with drug-resistant focal epilepsy. Double-blind and single-blind trials were eligible for inclusion. The primary outcome was 50% or greater reduction in seizure frequency; secondary outcomes were seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse effects, and proportion of individuals experiencing adverse effects.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and extracted the relevant data. Primary analyses were intention-to-treat (ITT). We presented summary risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs). We evaluated dose response in regression models. We carried out a risk of bias assessment for each included study using the Cochrane risk of bias tool and assessed the overall certainty of evidence using the GRADE approach.
MAIN RESULTS
We included 11 randomised controlled trials (3949 participants). Nine trials compared pregabalin to placebo. For the primary outcome, participants randomised to pregabalin were significantly more likely to attain a 50% or greater reduction in seizure frequency compared to placebo (RR 1.95, 95% CI 1.40 to 2.72, 9 trials, 2663 participants, low-certainty evidence). The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 1.99, 95% CI 1.74 to 2.28), indicating a dose-response relationship. Pregabalin was significantly associated with seizure freedom (RR 3.94, 95% CI 1.50 to 10.37, 4 trials, 1125 participants, moderate-certainty evidence). Participants were significantly more likely to withdraw from pregabalin treatment than placebo for any reason (RR 1.33, 95% CI 1.10 to 1.60; 9 trials, 2663 participants; moderate-certainty evidence) and for adverse effects (RR 2.60, 95% CI 1.86 to 3.64; 9 trials, 2663 participants; moderate-certainty evidence). Three trials compared pregabalin to three active-control drugs: lamotrigine, eventrate and gabapentin. Participants allocated to pregabalin were significantly more likely to achieve a 50% or greater reduction in seizure frequency than those allocated to lamotrigine (RR 1.47, 95% CI 1.03 to 2.12; 1 trial, 293 participants) but not those allocated to eventrate (RR 0.94, 95% CI 0.80 to 1.11; 1 trial, 509 participants) or gabapentin (RR 0.96, 95% CI 0.82 to 1.12; 1 trial, 484 participants). We found no significant differences between pregabalin and lamotrigine for seizure freedom (RR 1.39, 95% CI 0.40 to 4.83). However, significantly fewer participants achieved seizure freedom with add-on pregabalin compared to eventrate (RR 0.50, 95% CI 0.30 to 0.85). No data were reported for this outcome for pregabalin versus gabapentin. We detected no significant differences in treatment withdrawal rate for any reason or due to adverse effects, specifically, during either pooled analysis or subgroup analysis. Ataxia, dizziness, somnolence, weight gain, headache and fatigue were significantly associated with pregabalin than in active control. We rated the overall risk of bias in the included studies as low or unclear due to the possibility of publication bias and lack of methodological details provided. We assessed all the studies to be at a high risk of funding bias as they were all sponsored by Pfizer. We rated the certainty of the evidence as very low to moderate using the GRADE approach.
AUTHORS' CONCLUSIONS
For people with drug-resistant focal epilepsy, pregabalin when used as an add-on treatment was significantly more effective than placebo at producing a 50% or greater seizure reduction and seizure freedom. Results demonstrated efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses, although there were issues with tolerability at higher doses. However, the trials included in this review were of short duration, and longer-term trials are needed to inform clinical decision-making. This review focused on the use of pregabalin in drug-resistant focal epilepsy, and the results cannot be generalised to add-on treatment for generalised epilepsies. Likewise, no inference can be made about the effects of pregabalin when used as monotherapy.
Topics: Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Humans; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 35349176
DOI: 10.1002/14651858.CD005612.pub5 -
Journal of the American Society of... Jul 2018Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially...
Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking. From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0-100, >100-200, >200-300, and >300 mg) and pregabalin (>0-100 and >100 mg). In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%-41%) and fall (26%-30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively. Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.
Topics: Accidental Falls; Aged; Analgesics; Emergency Service, Hospital; Female; Fractures, Bone; Gabapentin; Hospitalization; Humans; Male; Medicare; Mental Disorders; Middle Aged; Pregabalin; Proportional Hazards Models; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; United States
PubMed: 29871945
DOI: 10.1681/ASN.2018010096 -
Current Osteoporosis Reports Dec 2022In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system. (Review)
Review
PURPOSE OF REVIEW
In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system.
RECENT FINDINGS
Gabapentinoids, such as gabapentin (GBP) and pregabalin (PGB) were designed as antiepileptic reagents and are now commonly used as first-line treatment for neuropathic pain and increasingly prescribed off-label for other pain disorders such as migraines and back pain. GBP and PGB exert their analgesic actions by selectively binding the αδ auxiliary subunit of voltage-sensitive calcium channels, thereby inhibiting channel function. Numerous tissues express the αδ subunit where GBP and PGB can alter calcium-mediated signaling events. In tissues such as bone, muscle, and cartilage, αδ has important roles in skeletal formation, mechanosensation, and normal tissue function/repair that may be affected by chronic use of gabapentinoids. Long-term use of gabapentinoids is associated with detrimental musculoskeletal outcomes, including increased fracture risk. Therefore, understanding potential complications is essential for clinicians to guide appropriate treatments.
Topics: Humans; Calcium; Gabapentin; gamma-Aminobutyric Acid; Homeostasis; Pregabalin
PubMed: 36149592
DOI: 10.1007/s11914-022-00750-x -
Anesthesiology Aug 2020
Topics: Analgesics; Ataxia; Dizziness; Gabapentin; Humans; Pain, Postoperative; Pregabalin; Preoperative Care
PubMed: 32667153
DOI: 10.1097/ALN.0000000000003394 -
Drug Safety Jul 2023Pregabalin is an antiepileptic drug frequently prescribed to pregnant women. Risks of adverse birth and postnatal neurodevelopmental outcomes following prenatal exposure... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pregabalin is an antiepileptic drug frequently prescribed to pregnant women. Risks of adverse birth and postnatal neurodevelopmental outcomes following prenatal exposure to pregabalin are uncertain.
OBJECTIVE
To investigate the association between prenatal exposure to pregabalin and the risks of adverse birth and postnatal neurodevelopmental outcomes.
METHODS
This study was conducted using population-based registries in Denmark, Finland, Norway, and Sweden (2005-2016). We compared pregabalin exposure against no exposure to antiepileptics and against active comparators lamotrigine and duloxetine. We obtained pooled propensity score-adjusted estimates of association using fixed-effect and Mantel-Haenszel (MH) meta-analyses.
RESULTS
The total number of pregabalin-exposed births was 325/666,139 (0.05%) in Denmark, 965/643,088 (0.15%) in Finland, 307/657,451 (0.05%) in Norway, and 1275/1,152,002 (0.11%) in Sweden. The adjusted prevalence ratios (aPRs) with 95% confidence interval (CI) following pregabalin exposure versus no exposure were 1.14 (0.98-1.34) for major congenital malformations and 1.72 (1.02-2.91) for stillbirth, which attenuated to 1.25 (0.74-2.11) in MH meta-analysis. For the remaining birth outcomes, the aPRs were close to or attenuated toward unity in analyses using active comparators. Adjusted hazard ratios (95% CI) contrasting prenatal pregabalin exposure versus no exposure were 1.29 (1.03-1.63) for ADHD and attenuated when using active comparators, 0.98 (0.67-1.42) for autism spectrum disorders, and 1.00 (0.78-1.29) for intellectual disability.
CONCLUSIONS
Prenatal exposure to pregabalin was not associated with low birth weight, preterm birth, small for gestational age, low Apgar score, microcephaly, autism spectrum disorders, or intellectual disability. On the basis of the upper value of the 95% confidence interval, increased risks greater than 1.8 were unlikely for any major congenital malformation and ADHD. For stillbirth and most groups of specific major congenital malformations, the estimates attenuated in MH meta-analysis.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Stillbirth; Pregabalin; Cohort Studies; Premature Birth; Prenatal Exposure Delayed Effects; Intellectual Disability; Scandinavian and Nordic Countries; Anticonvulsants
PubMed: 37099261
DOI: 10.1007/s40264-023-01307-2 -
Drug Design, Development and Therapy 2023Perioperative multimodal analgesia can prevent chronic pain after breast cancer surgery. This study aimed to investigate the efficacy of combined perioperative oral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Perioperative multimodal analgesia can prevent chronic pain after breast cancer surgery. This study aimed to investigate the efficacy of combined perioperative oral pregabalin and postoperative esketamine in preventing chronic pain after breast cancer surgery.
METHODS
Ninety patients undergoing elective breast cancer surgery were randomized into the combined pregabalin and esketamine group (EP group) and the general anesthesia alone group (Control group). The EP group received 150 mg of oral pregabalin 1 h before surgery and twice daily for seven days postoperatively, and a patient-controlled analgesia pump after surgery that delivered 100 μg sufentanil + 1.25 mg/kg esketamine + 4 mg tropisetron in 100 mL saline solution intravenously. The Control group received placebo capsules before and after the surgery and routine postoperative analgesia (100 μg sufentanil + 4 mg tropisetron in 100 mL saline solution). The primary outcome was the incidence of chronic pain three and six months after surgery. Secondary outcomes included acute postoperative pain, postoperative opioid consumption, and incidence of adverse events.
RESULTS
The incidence of chronic pain in the EP group was significantly lower than in the Control group three (14.3% vs 46.3%, = 0.005) and six (7.1% vs 31.7%, = 0.009) months postoperatively. The rest numerical rating scale (NRS) pain scores 1-3 days postoperatively and coughing NRS pain scores 1-7 days postoperatively in the EP group were significantly lower than in the Control group (all ˂ 0.05). The cumulative sufentanil consumption in the EP group during postoperative 0-12, 12-24, and 24-48, 0-24, and 0-48 hours were significantly lower than in the Control group (all ˂ 0.05).
CONCLUSION
Combined perioperative oral pregabalin and postoperative esketamine effectively prevented chronic pain after breast cancer surgery, improved acute postoperative pain, and reduced postoperative opioid consumption.
Topics: Humans; Female; Breast Neoplasms; Pregabalin; Analgesics, Opioid; Chronic Pain; Saline Solution; Sufentanil; Tropisetron; Pain, Postoperative
PubMed: 37313456
DOI: 10.2147/DDDT.S413273 -
Scientific Reports Jun 2023We aimed to evaluate the potential anxiolytic effects of premedication with pregabalin, compared with diazepam and placebo. We conducted this non-inferiority,... (Randomized Controlled Trial)
Randomized Controlled Trial
We aimed to evaluate the potential anxiolytic effects of premedication with pregabalin, compared with diazepam and placebo. We conducted this non-inferiority, double-blind, randomized controlled trial in ASA classification I-II patients aged 18-70 years, scheduled for elective surgery under general anesthesia. They were allocated to receive pregabalin (75 mg the night before surgery and 150 mg 2 h before surgery), diazepam (5 and 10 mg in the same manner) or placebo. Preoperative anxiety was evaluated using verbal numerical rating scale (VNRS) and Amsterdam Preoperative Anxiety and Information Scale (APAIS) before and after premedication. Sleep quality, sedation level, and adverse effects were assessed as secondary outcomes. A total of 231 patients were screened and 224 completed the trial. The mean change (95%CI) in anxiety scores from before to after medication in pregabalin, diazepam, and placebo groups for VNRS were - 0.87 (- 1.43, - 0.30), - 1.17 (- 1.74, - 0.60), and - 0.99 (- 1.56, - 0.41), and for APAIS were - 0.38 (- 1.04, 0.28), - 0.83 (- 1.49, - 0.16), and - 0.27 (- 0.95, 0.40). The difference in change for pregabalin versus diazepam was 0.30 (- 0.50, 1.11) for VNRS and 0.45 (- 0.49, 1.38) for APAIS, exceeding the limit of inferiority for APAIS of 1.3. Sleep quality was statistically different between pregabalin and placebo groups (p = 0.048). Sedation in pregabalin and diazepam groups were significantly higher than placebo group (p = 0.008). No significant differences of other side effects, except dry mouth was higher in placebo group compared with diazepam (p = 0.006). The study filed to provide evidence at non-inferiority of pregabalin compared to diazepam. Furthermore, premedication with either pregabalin or diazepam did not significantly reduce the preoperative anxiety in comparison to placebo, despite the fact that both resulted in higher levels of sedation. Clinicians should weigh the benefits and risks of premedication with these 2 drugs.Thai Clinical Trials Registry: TCTR20190424001 (24/04/2019) Registry URL: https://www.thaiclinicaltrials.org/ .
Topics: Humans; Anti-Anxiety Agents; Pregabalin; Diazepam; Anxiety; Drug-Related Side Effects and Adverse Reactions; Anesthesia, General; Double-Blind Method
PubMed: 37322140
DOI: 10.1038/s41598-023-36616-0 -
The Journal of Clinical Psychiatry Oct 2018In different parts of the world, pregabalin is an approved treatment for neuropathic pain syndromes, fibromyalgia, partial-onset seizures, and generalized anxiety... (Review)
Review
In different parts of the world, pregabalin is an approved treatment for neuropathic pain syndromes, fibromyalgia, partial-onset seizures, and generalized anxiety disorder. Few studies have examined the safety of pregabalin exposure during pregnancy. Among 4 studies identified through a PubMed search conducted in September 2018, one small study (exposed n = 30) recorded a major malformation rate of 3.3%, which was similar to that in unexposed controls. Another small study (exposed n = 30) recorded increased rates of spontaneous abortion (23.3%), preterm birth (25.0%), and major malformations (7.7%), none of which reached statistical significance even in unadjusted analyses. A third study (exposed n = 116) identified a significantly increased rate of major malformations (6.0%) but no increase in the rates of other adverse birth outcomes. The fourth and largest study (exposed n = 477 and n = 174; 2 datasets), which also presented the best statistical analysis, found no increase in the major malformation risk associated with pregabalin exposure. A subjective conclusion is that there is no clear signal that pregabalin exposure during pregnancy is associated with adverse gestational outcomes; however, this conclusion is limited by the consideration that all analyses were underpowered. Pregabalin use in pregnancy is therefore best restricted to circumstances in which the risk-benefit ratio is clearly favorable, and then, only after shared decision-making.
Topics: Female; Humans; Pregabalin; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 30289631
DOI: 10.4088/JCP.18f12568 -
Daru : Journal of Faculty of Pharmacy,... Dec 2020Herpes zoster is an acute, painful, herpes skin disease caused by varicella-zoster virus, which may cause viral meningitis. Pregabalin has been shown to be efficacious... (Review)
Review
Herpes zoster is an acute, painful, herpes skin disease caused by varicella-zoster virus, which may cause viral meningitis. Pregabalin has been shown to be efficacious in the treatment of pain in patients with herpes zoster. However, it has the side effects of neurotoxicity. We describe a 68-year-old female patient with herpes zoster, and she was treated with pregabalin. The patient presented with stuttering and frequent blepharospasm after 3 days of pregabalin treatment. Pregabalin was discontinued, the symptoms of stuttering and frequent blepharospasm completely resolved without any special treatment after one week. In this case, the etiology of stuttering and frequent blepharospasm may be related to pregabalin. Clinicians should be alert to the rare symptoms associated with the use of pregabalin. Graphical abstract .
Topics: Aged; Blepharospasm; Female; Herpes Zoster; Humans; Pregabalin; Stuttering; Treatment Outcome
PubMed: 32632575
DOI: 10.1007/s40199-020-00354-9 -
Revista Da Associacao Medica Brasileira... Mar 2022This study aimed to investigate the effects of duloxetine and pregabalin primarily on pain and functional status in patients with knee osteoarthritis and secondarily on... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This study aimed to investigate the effects of duloxetine and pregabalin primarily on pain and functional status in patients with knee osteoarthritis and secondarily on quality of life, depression, anxiety, and sleep disturbance.
METHODS
A total of 66 patients with knee osteoarthritis were randomized to use duloxetine or pregabalin. Patients were evaluated by Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36, Beck Depression Inventory, Beck Anxiety Inventory, and Pittsburg Sleep Quality Index before the treatment and after 4 and 12 weeks of treatment.
RESULTS
Improvements occurred in Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36 (with an exception of the mental health subgroup scores in duloxetine-treated group), Beck Depression Inventory, and Beck Anxiety Inventory scores in both groups from 4 weeks after baseline. Pittsburg Sleep Quality Index total scores and SF-36 mental health subgroup scores started to improve on the 4th and 12th weeks in pregabalin- and duloxetine-treated groups, respectively.
CONCLUSION
Osteoarthritis pain, a complex outcome with nociceptive and neuropathic components, leads to central sensitization in a chronic phase. Using centrally acting drugs in the control of pain and associated symptoms would increase the probability of treatment success.
Topics: Duloxetine Hydrochloride; Humans; Neuralgia; Osteoarthritis, Knee; Pregabalin; Quality of Life; Treatment Outcome
PubMed: 35442367
DOI: 10.1590/1806-9282.20211047