Efficacy and safety of pregabalin in eye pain: A systematic review.

To evaluate the effects of adjunctive pregabalin 300 mg/day versus placebo on polysomnographic (PSG) variables in patients with well controlled partial seizures and subjectively reported sleep disturbance. An exploratory, 4-week, double-blind, randomized study in patients with well controlled partial seizures on AED monotherapy and subjective sleep disturbance over the previous 6 months. Mean changes from baseline to endpoint in PSG and subjective sleep variables (MOS Sleep Scale, Groningen Sleep Questionnaire) in patients on adjunctive pregabalin 300 mg/day (n=8) were compared with patients on placebo (n=7). Baseline PSGs showed sleep fragmentation. Mean sleep efficiency improved significantly in both treatment groups in the mean baseline to endpoint change; there was no significant between-group difference. Pregabalin treatment was associated with a significant reduction in number of awakenings (p = 0.02), and improvement in wake time after sleep onset approached significance (p = 0.055), suggesting improvement in sleep continuity that was not observed in the placebo group. Pregabalin was also associated with significant improvements in the MOS sleep disturbance and sleep quantity subscales compared with placebo (p < or =0.03). There were no changes in self-reported seizure control. This exploratory pilot study suggests that pregabalin may improve sleep continuity in patients with clinically relevant sleep disturbance. The effect on disturbed sleep appears independent of seizure control. The effects of pregabalin on disturbed sleep and seizures and their interrelationships warrant further study.

Safety and efficacy of pregabalin in patients with central post-stroke pain

Pregabalin is a novel compound that has been shown to have efficacy in the treatment of generalised anxiety disorder and is licensed for the treatment of the disorder in the European Union. The current study was designed to evaluate the safety and efficacy of pregabalin, an alpha(2)delta-ligand, in the treatment of generalised anxiety disorder in people 65 years and older. This was a double-blind, randomised (2:1), placebo-controlled, 8-week trial of pregabalin, in flexible doses of 150-600 mg/day, in the treatment of DSM-IV generalised anxiety disorder with a baseline Hamilton Rating Scale for Anxiety (HRSA) total score >/=20. The primary outcome was end-point (week 8 or last visit, with last observation carried forward (LOCF)) change in HRSA total score. A total of 273 patients (women, 78%; mean age, 72 years (s.d.=6); mean baseline HRSA total score, 26 (s.d.=4.6)) were randomised and received study treatment. On the primary intent-to-treat LOCF analysis, pregabalin was associated with a 2-point greater reduction in HRSA total score than placebo (12.87 v. 10.7; P<0.05). In a post hoc repeated measures mixed-effect model analysis, pregabalin was associated with significantly greater improvement than placebo in the HRSA total score from week 2 (-9.8 (s.d.=0.6) v. -7.2 (s.d.=0.8); P=0.0052) through week 8 (-14.4 (s.d.=0.6) v. -11.6 (s.d.=0.8); P=0.0070). Significant improvement was observed in the pregabalin group on both the HRSA psychic and somatic anxiety factors. There was a significantly greater decrease from baseline in mean Hamilton Rating Scale for Depression (HRSD) score with pregabalin compared with placebo (-5.48 (s.d.=0.46) v. -4.02 (s.d.=0.59); P=0.041). Pregabalin was well-tolerated, with almost all adverse events in the mild-to-moderate range, and self-limiting (median duration of 4-16 days). Discontinuations due to adverse events were similar for pregabalin (10.7%) and placebo (9.4%). Pregabalin, in doses of 150-600 mg/day, was a safe and effective treatment of generalised anxiety disorder in patients 65 years and older. The anxiolytic efficacy of pregabalin had an early onset (by 2 weeks) and significantly improved both psychic and somatic symptoms of anxiety.

To study the efficacy of pregabalin for relapse prevention and reduction of drinking in patients with alcohol dependence. One hundred recently detoxified out-patients with alcohol dependence were randomly assigned to one of two treatment groups. Patients of the first group (n=50; 38 men, 12 women, age 43.0±1.27) received pregabalin (150 mg once a day at night time) for 3 months, while patients of the second group (n=50; 45 men, 5 women, age 45.92±1.4) received identically looking placebo. All patients received standardized manualized weekly counseling (medical management). Drinking was measured on the weekly basis with Time Line Follow Back technique and GGT enzyme activity. Also, craving for alcohol, depression, and anxiety were measured weekly with the number of scales. Kaplan-Meier survival analysis demonstrated significantly higher retention in treatment and in remission in the pregabalin group (lower drop out and relapse rate) mediana (CL)-12 (10.4-13.6) weeks in the pregabalin group vs. 6 (4.5-7.5) in the placebo group, Log Rank Mantel-Cox test = 0.005). Proportion of patients, who completed treatment in the pregabalin group, was significantly higher compared to the placebo group: 50% vs. 24%. Mean duration of participation in the treatment program was also higher in the pregabalin group: 9.1±0.5 weeks vs. 7.1±0.5 in the placebo group. General linear model demonstrated the significant treatment group effect on: (1) total alcohol consumption (TAC) (mean grams of alcohol per day) with lower TAC in the pregabalin group and (2) on the number of heavy drinking days (NHDD) with lower NHDD in the pregabalin group. Mean NHDD per patient for the period of participation in the study was lower in the pregabalin group (3.6±0.7 vs. 6.4±0.8; p=0.009), while the mean number of abstinent (sober) days was higher (55.9±3.6 vs. 40.0±3.3; p=0.001). No significant differences between the two groups were found in the scores on craving for alcohol, depression and anxiety scales. GGT activity was also similar in both groups throughout the study with no significant between group differences. The rate of adverse events (sleepiness, dizziness, and headache) was insignificantly higher in the pregabalin group compared with the placebo group. All adverse events were mild, gradually disappeared, and did not require any medication. Results of this study provide evidence that pregabalin in a low dose of 150 mg per day is an effective and safe medication for relapse prevention and reduction of drinking in patients with alcohol dependence.

Objective To examine the efficacy and safety of pregabalin in patients with neuropathic cancer pain (NCP). Methods A prospective randomized control multicenter trial was conducted in five hospitals; from January 2015 to January 2016, one hundred and twenty two eligible inpatients and outpatients were divided into pregablin treatment group (n=60) and control group (n=62). Patients in the pregablin group added pregablin to opiod background analgesia, while those in the control group raised opioid dose instead. The Numerical Pain Rating Scale (NRS) scores, paraesthesia scale scores, Hamilton's Depression (HAMD) scale scores, analgesia dose, patiends satisfaction, and adverse events were recorded 14 d after each treatment. Results After each treatment, the NRS scores were decreased by (2.3±1.1) and (1.3±1.5), the paraesthesia scale scores were decreased by (1.6±0.6) and (0.4±0.3), and the HAMD scale scores were decreased by (4.4±1.2) and (2.4±1.0) in thepregablin treatment group and control group, respectively, with significant differences (P<0.05). Morphine dose for breakthrough pain in pregabalin group was statistically less than that in control group ([30.6±3.5] mg/d vs. [70.9±12.3] mg/d, P<0.05). Patients satisfaction in the pregablin treatment group was significantly higher than that in the control group (P<0.05). Pregabalin treatment group had less severe adverse effects (3/56, 5%) as compared with control group (10/59, 16.1%, P<0.05). Conclusion Pregabalin has positive roles in patients with NCP already receiving opioid; pregabalin has better pain-control and mood improvement. Key words: Neuropathic cancer pain; Pregabalin; Opioid

We evaluated the efficacy of perioperative pregabalin on acute and chronic post-operative pain after off-pump coronary artery bypass (OPCAB) surgery. Forty patients undergoing elective OPCAB surgery were randomized to pregabalin and control groups. Pregabalin group received 150 mg pregabalin 2 h prior to induction of anesthesia and 75 mg twice daily for 2 post-operative days whereas the control group received placebo at similar timings; pregabalin and placebo were administered by an anesthesiologist blinded to the drugs. Pain scores (visual analogue scale [VAS]) and sedation scores were observed at 0, 4, 6, 12, 24, 36 and 48 h after extubation. Time to extubation, tramadol consumption and side-effects were noted. VAS score was analyzed by Mann-Whitney U test. The analysis of variance test for repeated measures was used for comparison of the means of continuous variables. Group comparisons were made using the Chi-square-test. Pain-scores at 6, 12, 24 and 36 h from extubation at rest and at deep breath were less in pregabalin treated patients ( P < 0.05). Tramadol consumption was reduced by 60% in pregabalin group ( P < 0.001). Extent of sedation, extubation times and incidence of nausea were comparable. The effect on chronic post-operative pain was not significant. Perioperative pregabalin reduced pain scores at rest and deep breath and reduced consumption of tramadol in the post-operative period without delaying extubation and causing excessive sedation.

ObjectiveTo examine the association between clinical trial registration and risk of bias in clinical trials that have been included in systematic reviews. As a secondary objective, we evaluated the risk of bias among trials registered prospectively vs. retrospectively. MethodClinical trials published in 2005 or after included in a sample of 100 Cochrane systematic reviews published from 2014-2019. ResultsOf 1,177 clinical trials identified, we verified 368 (31%) had been registered, of which 135 (36.7%) were registered prospectively (i.e., before or up to 1 month after enrollment of the first participant). Across the bias domains (one bias assessment for each domain per trial), the percentage of trials at low risk ranged from 29% to 58%; unclear risk ranged from to 26% to 61% and high risk ranged from 2% to 38%. Trials that had been registered had less high or unclear risk of bias in five domains: random sequence generation (univariate risk ratio [RR] 0.69, 95% confidence interval [95% CI] 0.58-0.81), allocation concealment (RR 0.64, 95% CI 0.57-0.72), performance bias (RR 0.65, 95% CI 0.58-0.72), detection bias (RR 0.70, 95% CI 0.62-0.78), and reporting bias (RR 0.62, 95% CI 0.53-0.73). An association between clinical trial registration and high or unclear risk of attrition bias could not be demonstrated nor refuted (RR 1.02, 95% CI 0.89-1.17). It also was observed in terms of overall risk of bias, that registered trials had less high or unclear overall risk of bias than trials that had not been registered (univariate RR 0.29, 95% CI 0.19-0.46). Prospective clinical trial registration was associated with low risks of selection bias due to inadequate allocation concealment, performance bias, and detection bias compared with retrospective clinical trial registration. ConclusionIn a large sample of clinical trials included in recently published systematic reviews of interventions, clinical trial registration was associated with low risk of bias for five of the six domains examined.

Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for acute lumbar radicular pain accompanying lumbar disc herniation (LDH), but their effects are minimal. The purpose of this study was to evaluate the efficacy and safety of pregabalin (PGB) as an alternative therapy for this condition. Methods Patients with acute lumbar radicular pain accompanying LDH were randomly administered either NSAIDs plus PGB (30 patients) or NSAIDs alone (30 patients) for up to 4 weeks. The primary outcome was leg pain at 2 and 4 weeks. Secondary outcomes were reduction in sleep disturbances and patient global impressions of change (PGIC) at 2 and 4 weeks. Results Four patients in the NSAIDs plus PGB group were deemed ineligible and excluded from the study. Fewer sleep disturbances were reported by patients administered NSAIDs plus PGB compared with the NSAID monotherapy group at both 2 and 4 weeks. Additionally, the NSAIDs plus PGB group showed greater improvement in pain than the NSAID monotherapy group at 4 weeks, although this difference was not significant. PGIC was also significantly better in the NSAIDs plus PGB group than in the NSAID monotherapy group at 4 weeks. The incidence of adverse events was significantly greater in the NSAIDs plus PGB group than in the NSAID monotherapy group. Conclusions The combination of NSAIDs plus PGB is more effective against sleep disturbance than NSAIDs alone in patients with acute LDH, although the control of sciatic pain is minimal. Patients reported satisfactory recoveries could also be obtained, and thus, this combination therapy could be a good option for the conservative treatment of acute lumbar radicular pain, including LDH.

Efficacy and safety of pregabalin in patients with neuropathic pain due to spinal cord injury: a pooled analysis

Objective To examine how poor reporting and inadequate methods for key methodological features in randomised controlled trials (RCTs) have changed over the past three decades.Design Mapping of trials included in...

Objective:To evaluate the efficacy and safety of carbamazepine, pregabalin, and venlafaxine in patients with painful diabetic neuropathy (PDN).Methods:Our study was performed as a randomized, double-blind, parallel-group clinical trial between December 2012 and December 2013 at Kermanshah University of Medical Sciences, Kermanshah, Iran. Two hundred and fifty-seven patients with clinically definite PDN were randomized to receive, carbamazepine, venlafaxine, or pregabalin. The primary outcome was subjective pain as assessed by the visual analogue scale (VAS). Secondary outcomes consisted of sleep, mood, and work interference assessments, and a percentage of patients achieving at least 50% reduction in pain intensity.Results:Means of VAS scores for carbamazepine, pregabalin, and venlafaxine treatment groups at the baseline (74.5, 82.3, and 74.5) and endpoint (39.6, 33.4, and 46.6) revealed significant reduction, although pregabalin was more efficacious than carbamazepine, and venlafaxine. Improvements in means scores of sleep, mood, and work interferences were identified in all treatment groups.Conclusion:This study showed the efficacy of venlafaxine, pregabalin, and carbamazepine in pain reduction in patients with diabetic neuropathy, although pregabalin was shown to be superior to carbamazepine, and venlafaxine in relieving pain, no significant superiority was shown between carbamazepine, and venlafaxine.

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.

The growing need for symptomatic treatment of post-traumatic neuropathic pain (PTNP) continues to be unmet. Studies evaluating the efficacy of pregabalin for reducing neuropathic pain following trauma and surgery yielded positive results over ≤ 8-week treatment. To assess the efficacy and tolerability of pregabalin over 3 months in patients with PTNP, a randomized, double-blind, placebo-controlled, parallel-group trial evaluated patients with PTNP at 101 centers in 11 countries—the longest, largest such trial. Adults diagnosed with PTNP were randomly assigned (1:1) to 15 weeks of pregabalin (flexibly dosed 150–600 mg/day) or matching placebo. Primary efficacy analysis was by mixed-model repeated measures comparing change from baseline to week 15 in weekly mean pain scores between active and placebo groups. Evaluable patients included 274 in the pregabalin group and 265 in the placebo group. Trauma was surgical in 49.6% of patients, non-surgical in the remainder. The primary efficacy analysis showed no statistically significant difference between pregabalin and placebo groups in the change from baseline to week 15 [mean difference, − 0.22 points (95% confidence interval, 0.54–0.10); p = 0.1823]. However, comparisons for key secondary outcome measures yielded p values < 0.05 favoring pregabalin. Consistent with the known safety profile of pregabalin, the most common adverse events were dizziness and somnolence (14.6 and 9.9% of patients, respectively) with pregabalin (vs 4.2 and 3.4% with placebo). These findings demonstrate the feasibility of conducting a large, phase 3 registration trial in the heterogeneous PTNP study population.ClinicalTrials.gov NCT01701362.

BackgroundOlder patients are typically underrepresented in clinical trials of medications for chronic pain. A post hoc analysis of multiple clinical studies of pregabalin in patients with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN) was conducted to evaluate the efficacy and safety of pregabalin in older patients.MethodsData from 11 double-blind, randomized, placebo-controlled clinical studies of pregabalin in patients with DPN or PHN were pooled. Efficacy outcomes included change in Daily Pain Rating Scale score, ≥30% and ≥50% responders, and endpoint pain score ≤3. Safety was based on adverse events (AEs). Primary efficacy was analyzed by analysis of covariance with terms for treatment, age category, protocol, baseline pain, and treatment-by-age category interaction.Results2516 patients (white, n = 2344 [93.2%]; men, n = 1347 [53.5%]; PHN, n = 1003 [39.9%]; pregabalin, n = 1595) were included in the analysis. Patients were grouped by age: 18 to 64 years (n = 1236), 65 to 74 years (n = 766), and ≥75 years (n = 514). Baseline mean pain and sleep interference scores were comparable across treatment and age groups. Significant improvements in endpoint mean pain were observed for all pregabalin dosages versus placebo in all age groups (p ≤ 0.0009), except for the lowest dosage (150 mg/day) in the youngest age group. Clinically meaningful pain relief, defined as ≥30% and ≥50% pain response, was observed in all age groups. The most common AEs were dizziness, somnolence, peripheral edema, asthenia, dry mouth, weight gain, and infections. The relative risks for these AEs increased with pregabalin dose, but did not appear related to older age or type of neuropathic pain.ConclusionsPregabalin (150-600 mg/day) significantly reduced pain in older patients (age ≥65 years) with neuropathic pain and improvements in pain were comparable to those observed in younger patients. Titration of pregabalin to the lowest effective dose should allow for effective pain relief while minimizing AEs in older patients with neuropathic pain. Given the common use of polypharmacy in older patients, the absence of known drug-drug interactions makes pregabalin an important treatment option for older patients with pain of neuropathic origin.

Pregabalin has been considered to be a safe treatment for neuropathic pain. Owing to the lack of research regarding the use of pregabalin in the management of pain in under-resourced settings, our study aimed to deduce the effectiveness of a pre-emptive single dose of pregabalin pre-operatively to provide pain relief after laparoscopic cholecystectomy. Treating acute pain is essential to avoid an increased hospital stay. There is a need for non-opioid drugs with lower risks to avoid using opioids, which lead to many side effects.MethodologyPatients diagnosed with cholelithiasis and scheduled to undergo laparoscopic cholecystectomy at the Abbasi Shaheed Hospital were included in this study. The study aimed to determine whether the effect of pregabalin in combination with patient-controlled analgesia can decrease pain scores. This was a double-blind study where patients, caregivers, and analysts were blinded to group allocation and drugs administered until the data was recorded and sealed. The patients were divided into pregabalin and placebo groups through a web-based model; blocks of four were used and stratification was employed at the center. A confidence interval of 95% was considered significant.ResultsIn our study, a total number of 60 patients were included. They were randomly divided by a computer-based model into two groups, the pregabalin group, and the control group. The placebo group had 33 patients while the pregabalin group had 27 patients. The pregabalin group was given a pregabalin tablet of 150 mg before surgery while the placebo group was given an identical-looking placebo. Patient-controlled analgesia was started in both groups and the visual analog scale (VAS) scoring was observed postoperatively. The pregabalin group had a decreased incidence of pain as compared to the placebo group. There were no significant side effects during the trial; episodes of vomiting were managed using intravenous ondansetron.ConclusionPregabalin is effective in reducing pain in an acute postoperative period when compared with a placebo. Patients who were pre-emptively administered pregabalin reported decreased VAS as compared to the placebo. However, both were inefficient in reducing postoperative nausea and vomiting.