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Refractory chronic cough causes substantial symptoms and quality-of-life impairment. Similarities between central reflex sensitisation in refractory chronic cough and neuropathic pain suggest that neuromodulators such as gabapentin might be effective for refractory chronic cough. We established the efficacy of gabapentin in patients with refractory chronic cough. This randomised, double-blind, placebo-controlled trial was undertaken at an outpatient clinic in Australia. Adults with refractory chronic cough (>8 weeks' duration) without active respiratory disease or infection were randomly assigned to receive gabapentin (maximum tolerable daily dose of 1800 mg) or matching placebo for 10 weeks. Block randomisation was done with randomisation generator software, stratified by sex. Patients and investigators were masked to assigned treatment. The primary endpoint was change in cough-specific quality of life (Leicester cough questionnaire [LCQ] score) from baseline to 8 weeks of treatment, analysed by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12608000248369. 62 patients were randomly assigned to gabepentin (n=32) or placebo (n=30) and ten patients withdrew before the study end. Gabapentin significantly improved cough-specific quality of life compared with placebo (between-group difference in LCQ score during treatment period 1·80, 95% CI 0·56–3·04; p=0·004; number needed to treat of 3·58). Side-effects occurred in ten patients (31%) given gabapentin (the most common being nausea and fatigue) and three (10%) given placebo. The treatment of refractory chronic cough with gabapentin is both effective and well tolerated. These positive effects suggest that central reflex sensitisation is a relevant mechanism in refractory chronic cough. National Health and Medical Research Council of Australia and Hunter Medical Research Institute, Newcastle, Australia.

Sevoflurane causes emergence agitation (EA) in up to 80% of pediatric patients. Using midazolam, dexmedetomidine (DEX), and gabapentin, this work aimed to assess the prophylactic effect of oral premedication on EA incidence experienced by pediatric patients during recovery from sevoflurane anesthesia. Randomized controlled trial. Kafrelsheikh University, Kafrelsheikh, Egypt. This study was performed on 240 men and women aged 3 to 10 years who were scheduled for adenotonsillectomy. Patients were randomized into 4 equal-sized groups. Thirty minutes before general anesthesia, oral premedication was applied in the form an apple-flavored sugary fluid plus 0.5 mg/kg of midazolam in Group M, 4 µg/kg of DEX in Group D, 10 mg/kg of gabapentin in Group G, or no drugs whatsoever in Group P (placebo). The incidence of EA was reduced more greatly in the M, D, and G groups than in the P group, and the D group's incidence of EA was lower than that of the M or G groups. The severity of EA exhibited a more significant reduction in the M, D, and G groups than in Group P. Similarly, the time until extubation was more prolonged in the M, D, and G groups than it was in the P group. Hemodynamics measurements were significantly lower in Groups M, D, and G than in Group P, and the D group had a lower hemodynamics measurement than did the M or G groups. Sedation scores were greater in the D and G groups than in the P group, and the D group had a higher sedation score than did Group M. This study used a small sample, took place at a single center, and had a short follow-up period. Premedication using oral midazolam, DEX, or gabapentin reduced the incidence of EA, and DEX provided the best sedation and hemodynamics of all.

Background Pruritus is a common skin symptom manifesting with an unpleasant sensation and desire to itch and scratch. Pruritis can be a hallmark of many skin diseases as well as other non cuatneous diseases. Aim of the study To compare the efficacy of gabapentin versus narrow band UVB versus combination of both in treatment of uremic pruritus. Methods This study that included 60 patients diagnosed with uremic pruritus, randomly allocated into one of three groups. Group A received oral gabapentin 300 mg OD for six weeks, group B received NB-UVB phototherapy three times per week in nonconsecutive days for a total of 18 sessions (6 weeks) and group C received combination of both therapies for 6 weeks. Efficacy was assessed by visual analogue scale (VAS) and 5-D itch scale before and after the end of therapy. Results Significant difference of VAS score between groups A & C ( P  = 0.029) and between group B & C ( P  = 0.027) was demonstrated. Complete responders represented 55% of group C (combination treatment group), 20% of group A & only 15% of group B. The highest frequency of no response was detected for group A (30%) followed by group B (15%) and lowest for group C (5%). Conclusion Combination of both gabapentin and NB-UVB is a promising medication for the treatment of uremic pruritus. Further well-designed clinical and experimental studies are needed to clarify the relationship between the frequency of NB-UVB phototherapy sessions and gabapentin dosing for an optimal response.

Summary Background MK-5108 is a potent/highly selective Aurora A kinase inhibitor. Methods A randomized Phase I study of MK-5108, administered p.o. BID Q12h on days 1–2 in 14–21 day cycles either alone (MT; Panel1/ n  = 18; 200 to 1800 mg) or in combination (CT; Panel2/ n  = 17; 100 to 225 mg) with IV docetaxel 60 mg/m 2 , determined the maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (Panel1, only) and tumor response in patients with advanced solid tumors. This study was terminated early due to toxicities in Panel2 at MK-5108 doses below the anticipated PK exposure target. Results 35 patients enrolled (33 evaluable for tumor response). No dose-limiting toxicities (DLTs) were observed in Panel1; three patients had 3 DLTs in Panel2 (G3 and G4 febrile neutropenia at 200 and 450 mg/day, respectively; G3 infection at 450 mg/day). In Panel1, AUC 0-12hr and C max increased less than dose proportionally following the first MT dose but increased roughly dose proportionally across 200 to 3600 mg/day after 4th dose. The t 1/2 ranged from 6.6 to 13.5 h across both panels. No clear effects on immunohistochemistry markers were observed; however, significant dose-related increases in gene expression were seen pre-/post-treatment. Best responses were 9/17 stable disease (SD) (Panel1) as well as 1/16 PR and 7/16 SD (Panel2) (450 mg/day). Conclusions MK-5108 MT was well tolerated at doses up to 3600 mg/day with plasma levels exceeding the minimum daily exposure target (83 μM*hr). The MTD for MK-5108 + docetaxel (CT) was established at 300 mg/day, below the exposure target. Use of pharmacodynamic gene expression assays to determine target engagement was validated.

Purpose Gabapentin was investigated as a single-dose adjunct to morphine for postoperative pain management. The primary objective was to determine if gabapentin given preoperatively and for two days postoperatively as part of multimodal analgesia would decrease postoperative morphine consumption in patients undergoing primary total hip arthroplasty (THA). Methods The study group included 102 patients aged 19-90 years who were undergoing primary THA in a single joint with no contraindications to the study medications, no chronic pain syndrome, and no chronic opioid use. Intervention group patients ( n  = 48) received gabapentin 600 mg po preoperatively and 200 mg postoperatively on the day of surgery. They were continued on gabapentin at 200 mg three times daily for two days. Control group patients ( n  = 54) received placebo in a similar fashion. Preoperatively, all patients were given 30 mg of ketorolac intravenously and acetaminophen 1000 mg po . Postoperatively, they received intravenous patient-controlled analgesia with morphine, along with ketorolac 15 mg iv and acetaminophen 1000 mg po every six hours. Results The primary outcome was mean (SD) postoperative morphine consumption at 72 hr which was 55.8 (39.2) mg in the gabapentin groups vs 60.7 (37.2) mg for the control group (mean difference, −4.91 mg, 95% confidence intervals [CI]: −21.2 to 11.35; P  = 0.550). There were no significant differences between the groups regarding secondary outcomes: pain scores, side effects, range of motion. Patient satisfaction on day 3 was more favourable in the placebo group. Length of hospitalization was marginally shorter in the placebo group. Conclusions This trial indicated that gabapentin treatment had no clinically important reduction in postoperative morphine consumption at 72 hr in patients undergoing THA. Multimodal analgesia may account for the similar primary and secondary outcomes found in the groups. This trial was registered at ClinicalTrials.gov, number: NCT01307202.

Purpose This study assessed whether gabapentin given preoperatively and for two days postoperatively (in addition to patient-controlled analgesia [PCA] morphine, acetaminophen, and ketorolac) is effective in reducing morphine requirements and moderating pain scores when compared with placebo for primary total knee arthroplasty. Methods This single-centre double-blind randomized controlled trial was undertaken in patients who underwent primary total knee arthroplasty. All subjects received acetaminophen 1,000 mg and ketorolac 15 mg po preoperatively. Postoperatively, subjects received PCA morphine, acetaminophen 1,000 mg every six hours, and ketorolac 15 mg po every six hours. Subjects received either gabapentin 600 mg po preoperatively followed by 200 mg po every eight hours for two days or matching placebo. The primary outcome was cumulative morphine consumption at 72 hr following surgery. Secondary outcome measures included pain scores and patient satisfaction. Results There were 52 subjects in the gabapentin group and 49 subjects in the placebo group. The average cumulative morphine consumption at 72 hr postoperatively was 66.3 mg in the gabapentin group and 72.5 mg in the placebo group (difference −6.2 mg; 95% confidence interval −29.1 to 16.8 mg; P  = 0.59). Mean pain scores at rest, with passive movement, or with weight bearing were similar in both groups at corresponding time periods for the first three days following surgery. In addition, mean patient satisfaction scores and hospital length of stay were similar in the two groups. Conclusion Gabapentin 600 mg po given preoperatively followed by 200 mg po every eight hours for two days has no effect on postoperative morphine consumption, pain scores, patient satisfaction, or length of hospital stay. This trial is registered at ClinicalTrials.gov NCT01307202.

Rationale Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. Objectives This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. Methods Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. Results There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. Conclusions These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.

Introduction. Painful diabetic neuropathy (PDN) is a prevalent and impairing disorder. The objective of this study was to show the efficacy and safety of gabapentin (GBP) plus complex B vitamins: thiamine (B1) and cyanocobalamine (B12) compared to pregabalin in patients with moderate to severe intensity PDN. Method. Multicenter, randomized, blind study. Two hundred and seventy patients were evaluated, 147 with GBP/B1/B12 and 123 with PGB, with a 7/10 pain intensity on the Visual Analog Scale (VAS). Five visits (12 weeks) were scheduled. The GBP/B1 (100 mg)/B12 (20 mg) group started with 300 mg at visit 1 to 3600 mg at visit 5. The PGB group started with 75 mg/d at visit 1 to 600 mg/d at visit 5. Different safety and efficacy scales were applied, as well as adverse event assessment. Results. Both drugs showed reduction of pain intensity, without significant statistical difference (P=0.900). In the GBP/B1/B12 group, an improvement of at least 30% on VAS correlated to a 900 mg/d dose, compared with PGB 300 mg/d. Likewise, occurrence of vertigo was lower in the GBP/B1-B12 group, with a significant statistical difference, P=0.014. Conclusions. Our study shows that GPB/B1-B12 combination is as effective as PGB. Nonetheless, pain intensity reduction is achieved with 50% of the minimum required gabapentin dose alone (800 to 1600 mg/d) in classic NDD trials. Less vertigo and dizziness occurrence was also observed in the GBP/B1/B12 group. This trial is registered with ClinicalTrials.gov NCT01364298.

Background: Severe, intractable, chronic pain is a significant management problem for those involved in the long-term care of spinal cord injury (SCI) patients . Gabapentin, an anticonvulsant, is widely used for treating chronic pain. Ketamine, an NMDA receptor antagonist, has been available in clinical practice for 35 years. Its usefulness in pathological pain states is known. Despite this, no formal research on its effectiveness in treating neuropathic SCI pain exists. Objectives: This double-blind study sought to determine the safety and efficacy of adding a multi-day low dose ketamine infusion to oral gabapentin for treating chronic pain related to post spinal cord injury. Study Design: Randomized, controlled, double blind trial Setting: Hospital, in-patient setting. Methods: Forty patients diagnosed with neuropathic pain secondary to spinal cord injury were randomized into 2 equal groups. Group I received an 80 mg intravenous ketamine infusion diluted in 500 cc normal saline over a 5 hour period daily for one week and 300 mg of gabapentin 3 times daily. Group II received a placebo infusion and 300 mg of gabapentin 3 times daily (continued) after 300 mg of gabapentin 3 times daily. Using the visual analogue scale, pain was assessed prior to treatment, daily following ketamine or placebo infusions for 7 days, and then weekly for one month after infusion termination. Side effects, specifically those related to ketamine or gabapentin, were reported. Results: Both groups demonstrated significantly reduced pain scores compared with pretreatment values (P < 0.05). Group I showed significant pain score improvements over Group II at all measurements (P < 0.0001) during infusion and 2 weeks after infusion termination. There was no statistical difference between the groups at 3 weeks and 4 weeks after infusion termination (P = 0.54 and P = 0.25 respectively). Both drugs were tolerated by all patients; no side effects required intervention. Conclusion: Multi-day low dose ketamine infusion as adjuvant to gabapentin in post-spinal cord injury related chronic pain is safe and efficacious in reducing pain, but the effect compared to placebo ceased 2 weeks after infusion termination. Limitations: Study size limited to 40 patients. Key words: Ketamine, Gabapentin, Spinal, Pain, injury, chronic

Background Treatment of postherpetic neuralgia (PHN) is more complicated in elderly patients, and multiple daily dosing, complex titration, and high incidences of adverse events can be limiting for many pharmacological treatment options. Objective The aim of this study was to determine whether the efficacy and tolerability of once-daily gastroretentive gabapentin (G-GR) is similar between elderly patients (≥75 years) and younger patients (<75 years). Methods Data from two phase III, placebo-controlled studies of 1,800 mg G-GR once daily with dinner in patients with PHN were integrated and analyzed by age subgroups (<75 years, n  = 527; ≥75 years, n  = 192). Efficacy assessments at endpoint (week 10) included baseline-adjusted change in average daily pain (ADP) and average daily sleep interference (SIS) scores, the proportion of responders (≥30 % pain reduction), and the proportion of patients feeling “Much” or “Very Much” improved on the Patient Global Impression of Change (PGIC). Results Compared with placebo, patients in both age subgroups treated with G-GR (placebo/G-GR) had greater reductions in mean ADP (≥75: −21.9/−34.2 %, p  = 0.0348; <75: −29.9/−38.3 %, p  = 0.0079) and SIS (≥75: −1.3/−2.4, p  = 0.0017; <75: −1.8/−2.7, p  < 0.0001), more patients were responders (≥75: 30.4/52.0 %, p  = 0.0025; <75: 45.0/54.7 %, p  = 0.0265), and more felt “Much” or “Very Much” improved on the PGIC (≥75: 20.7/35.0 %, p  = 0.0272; <75: 33.6/44.9 %, p  = 0.0077). The most common (placebo/G-GR) adverse events (AEs) were dizziness (≥75: 3.3/12.0 %; <75: 1.8/10.4 %), nausea (≥75: 1.0/5.4 %; <75: 2.9/4.2 %), and somnolence (≥75: 0/5.0 %; <75: 3.7/4.2 %). For all patients, AEs rapidly decreased to low steady levels after 4–5 weeks of treatment. The incidence of serious AEs was low and they were reported more frequently in the placebo than in the G-GR group. Conclusions Therapy with once-daily G-GR was as effective for treating pain associated with PHN in elderly patients as it was in younger patients. G-GR was well tolerated, and the incidence of the most common AEs did not appear to be age related.