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How to treat neuropathic pain
"How to treat neuropathic pain and tingling (parasthesias). A lecture by D. Campagnolo, MD."
A comparison of initial duloxetine dosing strategies in patients with major depressive disorder.
A comparison of initial duloxetine dosing strategies in patients with major depressive disorder. J Clin Psychiatry. 2007 Dec;68(12):1921-30 Authors: Whitmyer VG, Dunner DL, Kornstein SG, Meyers AL, Mallinckrodt CH, Wohlreich MM, Gonzales JS, Greist JH OBJECTIVE: To compare the effects of starting doses of duloxetine taken with or without food on tolerability and efficacy in patients with major depressive disorder (MDD). METHOD: This double-blind, concurrent-dose-controlled, parallel-design trial contained a variable expected-duration placebo lead-in period and was conducted in adult outpatients with DSM-IV-TR-defined MDD at psychiatric outpatient sites between October 2004 and January 2006. In actuality, patients received placebo for 1 week and then were randomly assigned to duloxetine 30 mg once daily in the morning (q.a.m.) (N = 219), 30 mg twice daily (b.i.d.) (N = 213), or 60 mg q.a.m. (N = 215) for 1 week along with 1 of 2 instructions about food: take study drug with food or do not take within 1 hour of eating. For the remaining 5 weeks of acute treatment, all patients received 60 mg once daily. The primary objective was to compare incidence of treatment-emergent nausea at 30 mg q.a.m. versus 60 mg q.a.m. using item 112 (nausea) of the Association for Methodology and Documentation in Psychiatry adverse event scale (AMDP-5). Secondary outcome measures included mean change on AMDP-5 item 112, discontinuations due to adverse events, mean changes in AMDP-5 items and subscales, spontaneously reported treatment-emergent adverse events, and vital signs. Efficacy was evaluated by the 17-item Hamilton Rating Scale for Depression (HAM-D-17). RESULTS: The primary analysis, which combined data from both food groups, showed no significant difference in the incidence of nausea between starting doses of 30 mg q.a.m. and 60 mg q.a.m. (23% vs. 29%, respectively; p = .207). However, mean changes on the AMDP-5 nausea item revealed a significant main effect of food (p = .010) and a significant interaction between food and starting dose (p = .033). The food-by-dose interaction indicated that the benefit from taking drug with food was greatest in patients started at 60 mg q.a.m., and the benefit of starting at 30 mg q.a.m. was greatest in patients taking drug without food. In patients who took study drug without food, there was a significant difference across initial-dose groups for discontinuation due to adverse events (30 mg q.a.m. = 3.6%, 30 mg b.i.d. = 14.0%, 60 mg q.a.m. = 10.2%; 30 mg q.a.m. vs. 30 mg b.i.d., p = .008; 30 mg q.a.m. vs. 60 mg q.a.m., p = .066); however, in patients who took study drug with food, discontinuations due to adverse events did not significantly differ (30 mg q.a.m. = 5.4%, 30 mg b.i.d. = 7.5%, 60 mg q.a.m. = 7.4%; all p values > .50). Patients who started at 30 mg b.i.d. or 60 mg q.a.m. without food did not differ regarding mean changes (i.e., increases) in the common adverse events score after 1 week of treatment but had significantly greater mean changes than patients who started at 30 mg q.a.m. without food (0.87, 0.82, and 0, respectively; p < .05 vs. 30 mg b.i.d. and 60 mg q.a.m.). No significant differences were found between initial-dose groups in vital signs. CONCLUSIONS: These data imply that starting dulox-etine at 30 mg q.a.m. for 1 week with or without food or starting duloxetine at the therapeutic dose of 60 mg q.a.m. with food can improve the initial tolerability of the medication. Adding this information to existing knowledge of duloxetine will enable the clinician to tailor therapy most appropriately for the individual patient. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT 00191061.
Treat neuropathic pain PMID: 18162024 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Gabapentin for painful legs and moving toes syndrome. Intern Med. 2007;46(23):1937 Authors: Aizawa H
Treat neuropathic pain PMID: 18057770 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Efficacy and safety of duloxetine 60 mg once daily in the treatment of pain in patients with major depressive disorder and at least moderate pain of unknown etiology: a randomized controlled trial. J Clin Psychiatry. 2007 Nov;68(11):1707-16 Authors: Brecht S, Courtecuisse C, Debieuvre C, Croenlein J, Desaiah D, Raskin J, Petit C, Demyttenaere K OBJECTIVE: Experience of pain in major depressive disorder (MDD) can complicate diagnosis and impair treatment outcomes. This study evaluated the efficacy and safety of duloxetine in the treatment of patients with moderate pain associated with depression. METHOD: In this double-blind, placebo-controlled, 8-week study, conducted from May 2005 to May 2006, outpatients 18 years of age or older, presenting with major depressive disorder (DSM-IV criteria; Montgomery-Asberg Depression Rating Scale [MADRS] score >or= 20), moderate pain (Brief Pain Inventory-Short Form [BPI-SF] average pain score >or= 3), and Clinical Global Impressions-Severity of Illness scale (CGI-S) score >or= 4 were randomly assigned to either placebo (N = 165) or duloxetine 60 mg (N = 162) once daily. Primary outcome was change in item 5 score (average pain in the last 24 hours) of the BPI-SF from baseline. Secondary measures were MADRS total score, other BPI-SF items, CGI-S, CGI-Improvement scale, Patient Global Impressions-Improvement scale, Symptom Checklist-90-Revised, response and remission rates, safety, and tolerability. RESULTS: Duloxetine, compared with placebo, significantly reduced pain and improved depression with significant mean changes at endpoint in both BPI-SF average pain scores (-2.57 vs. -1.64, p < .001) and in MADRS total scores (-16.69 vs. -11.31, p < .001). Remission of MDD and response rates in pain and MDD were significantly (p <or= .001) higher in duloxetine-treated patients. Duloxetine separated from placebo on most secondary outcome measures including the BPI-SF interference with daily life due to pain. Treatment-emergent adverse events (>or= 10%) in duloxetine-treated patients were nausea, hyperhidrosis, and dry mouth. CONCLUSION: These results support duloxetine's efficacy and tolerability in the treatment of pain and depression in patients with at least moderate pain associated with depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00191919 (http://www.clinicaltrials.gov).
Treat neuropathic pain PMID: 18052564 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007 Nov;68(11):1691-700 Authors: Furieri FA, Nakamura-Palacios EM OBJECTIVE: This study examined the efficacy of a 28-day gabapentin treatment in reducing alcohol consumption and craving. METHOD: A randomized, double-blind, placebo-controlled trial was performed in a Brazilian public outpatient drug treatment center, with 60 male alcohol-dependent subjects with a mean age of 44 years and an average of 27 years of alcohol use, who consumed 17 drinks per day (165-170 g/day) over the past 90 days before baseline and had no other significant medical or psychiatric condition. Subjects were recruited between July 8, 2004, and February 24, 2005. Following screening, 60 subjects were selected and received diazepam and vitamins as treatment for acute withdrawal for at least 7 days. After the detoxification treatment, 30 subjects were randomly assigned to receive gabapentin (300 mg twice daily) for 4 weeks, and 30 subjects, with similar baseline characteristics, were randomly assigned to receive matching placebo tablets for the same period. RESULTS: After 28 days of treatment, the gabapentin group showed a significant reduction in both number of drinks per day and mean percentage of heavy drinking days (p = .02 for both), and an increase in the percentage of days of abstinence (p = .008), compared to the placebo group. Additionally, some improvement in obsessive-compulsive symptoms was noted in both groups after the treatment, but it resulted in a more pronounced decrease in automaticity of drinking and aspects of craving in the gabapentin group than in the placebo group. CONCLUSION: Gabapentin reduces alcohol consumption and craving, which may help patients to maintain abstinence. These results, together with the virtual absence of side effects and a favorable safety profile, support gabapentin as a potential drug for the treatment of alcohol withdrawal and dependence.
Treat neuropathic pain PMID: 18052562 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury. Arch Phys Med Rehabil. 2007 Dec;88(12):1547-60 Authors: Rintala DH, Holmes SA, Courtade D, Fiess RN, Tastard LV, Loubser PG OBJECTIVE: To test the hypotheses that both amitriptyline and gabapentin are more effective in relieving neuropathic pain than an active placebo, diphenhydramine. DESIGN: Randomized, controlled, double blind, triple crossover 8-week trial. SETTING: Veterans Affairs medical center. PARTICIPANTS: Community dwelling adults with spinal cord injury (N=38) were recruited by telephone, letters, and flyers. INTERVENTION: Eight-week trial each of amitriptyline, gabapentin, and diphenhydramine. MAIN OUTCOME MEASURES: Pain intensity measured with a 10-cm visual analog scale (VAS) and an 11-point (0-10) numeric rating scale (NRS) and depressive symptomatology measured with the Center for Epidemiologic Studies Depression Scale-Short Form (CESD-SF). RESULTS: Baseline VAS scores for participants with low (< 10) CESD-SF scores was 4.61 and for those with high scores (> or = 10) it was 7.41. At week 8, in participants with high baseline CESD-SF scores, amitriptyline (mean, 4.21) was more effective than diphenhydramine (mean, 6.67; P=.035), and there was a nonsignificant trend suggesting that amitriptyline may be more effective than gabapentin (mean, 6.68; P=.061). Gabapentin was no more effective than diphenhydramine (P=.97). There was no significant difference among the medications for those with lower CESD-SF scores. Results could not be attributed to dropout rates, order or dose of medications, amount of medication taken for breakthrough pain, or side effects. CONCLUSIONS: Amitriptyline is more efficacious in relieving neuropathic pain than diphenhydramine at or below the level of spinal cord injury in people who have considerable depressive symptomatology.
Treat neuropathic pain PMID: 18047869 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pregabalin: its pharmacology and use in pain management. Anesth Analg. 2007 Dec;105(6):1805-15 Authors: Gajraj NM Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid. It is an alpha2-delta (alpha2-delta) ligand that has analgesic, anticonvulsant, anxiolytic, and sleep-modulating activities. Pregabalin binds potently to the alpha2-delta subunit of calcium channels, resulting in a reduction in the release of several neurotransmitters, including glutamate, noradrenaline, serotonin, dopamine, and substance P. In this review, I will discuss the pharmacology of pregabalin and available efficacy studies in pain management. This review will focus on the advances in pregabalin pharmacology since my previous review in 2005.
Treat neuropathic pain PMID: 18042886 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pregabalin in benzodiazepine withdrawal. Pharmacopsychiatry. 2007 Nov;40(6):292-3 Authors: Biermann T, Bleich S, Kornhuber J, Hillemacher T
Treat neuropathic pain PMID: 18030656 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Gabapentin: a multimodal perioperative drug? Br J Anaesth. 2007 Dec;99(6):775-86 Authors: Kong VK, Irwin MG Gabapentin is a second generation anticonvulsant that is effective in the treatment of chronic neuropathic pain. It was not, until recently, thought to be useful in acute perioperative conditions. However, a growing body of evidence suggests that perioperative administration is efficacious for postoperative analgesia, preoperative anxiolysis, attenuation of the haemodynamic response to laryngoscopy and intubation, and preventing chronic post-surgical pain, postoperative nausea and vomiting, and delirium. This article reviews the clinical trial data describing the efficacy and safety of gabapentin in the setting of perioperative anaesthetic management.
Treat neuropathic pain PMID: 18006529 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pregabalin in the management of central neuropathic pain. Expert Opin Pharmacother. 2007 Dec;8(17):3035-41 Authors: Gray P Central neuropathic pain is a painful condition, often severe, that occurs in a person who is already affected by an injury or disease of the brain or spinal cord. This dual insult is especially threatening to the quality of life of a person and their ability to perform even the most basic of tasks. Despite this high level of suffering there are relatively few trials investigating the management of central neuropathic pain. However, two randomised placebo-controlled studies have recently emerged demonstrating efficacy of pregabalin in reducing central neuropathic pain due to spinal cord injury and central poststroke pain. Pregabalin, an anticonvulsant, has been shown to be efficacious in the management of peripheral neuropathic pain of various causes and now may have a role to play in central neuropathic pain.
Treat neuropathic pain PMID: 18001262 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
An evaluation of the efficacy of gabapentin for prevention of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study. Anesth Analg. 2007 Nov;105(5):1454-7, table of contents Authors: Agarwal A, Dhiraaj S, Pawar S, Kapoor R, Gupta D, Singh PK BACKGROUND: Catheter-related bladder discomfort (CRBD) secondary to catheterization of urinary bladder is distressing. In the present study, we evaluated gabapentin for preventing CRBD. METHODS: One-hundred and eight consecutive adult patients, ASA physical status I and II, of either sex, undergoing elective percutaneous nephrolithotomy were randomized into two groups of 54 each. Group control: placebo and group G gabapentin: gabapentin 600 mg. Drugs were administered orally 1 h before surgery. After induction of anesthesia, patients were catheterized with a 16F Foley catheter and the balloon was inflated with 10 mL normal saline. In the postanesthesia care unit, the incidence and severity (mild, moderate, and severe) of CRBD were assessed on arrival (0) and at 1, 2, and 6 h. RESULTS: Gabapentin reduced the incidence of CRBD to 50% (27 of 54) compared with 80% (43 of 54) observed in the control group (P < 0.05). Gabapentin also reduced the severity of CRBD and postoperative pain as observed by a reduction in the number of patients requiring any fentanyl and the total fentanyl consumption postoperatively (P < 0.05). CONCLUSION: Gabapentin (600 mg) administered orally 1 h before surgery reduced the incidence and severity of CRBD, postoperative pain, number of patients requiring fentanyl and postoperative total fentanyl requirement.
Treat neuropathic pain PMID: 17959982 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery. Anesth Analg. 2007 Nov;105(5):1449-53, table of contents Authors: Paech MJ, Goy R, Chua S, Scott K, Christmas T, Doherty DA BACKGROUND: Although pregabalin shows efficacy against neuropathic pain, very limited evidence supports postoperative analgesic efficacy. Our study objective was to investigate analgesic efficacy in an ambulatory day surgical population experiencing acute visceral pain. The null hypothesis was that there was no significant difference in pain relief between pregabalin and placebo. METHODS: A randomized, double-blind, parallel-group, placebo-controlled trial was performed in 90 women having minor gynecological surgery involving the uterus. Patients received either oral pregabalin 100 mg (Group PG) or placebo (Group C) approximately 1 h before surgery. The primary outcome was pain score in the recovery unit and patients were followed for 24 h. RESULTS: There was no significant difference between groups for pain experienced in the recovery room (median, interquartile range 16, 0-36 vs 10, 6.5-36 for Groups PG and C, respectively, P = 0.80) or thereafter; nor for recovery room fentanyl requirement (42% Group PG versus 27% Group C, P = 0.12) or the quality of recovery at 24 h postoperatively (median, interquartile range score 17, 17-18 Group PG versus 18, 16.5-18 Group C, P = 0.75). The incidence of posthospital discharge light-headedness, visual disturbance, and difficulty with walking was significantly higher in the pregabalin group. CONCLUSIONS: A single preoperative dose of 100 mg pregabalin does not reduce acute pain or improve recovery after minor surgery involving only the uterus.
Treat neuropathic pain PMID: 17959981 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Gabapentin. Prog Brain Res. 2007;166:287-301 Authors: Bauer CA, Brozoski TJ Several lines of evidence suggest that loss of central inhibition after deprivation of input from the ear (peripheral deafferentation) may be one cause of chronic tinnitus. Aging and acoustic trauma, the two most common causes of peripheral damage to the auditory system, each decrease input to central auditory structures. Loss of input to tonic inhibitory systems would release excitatory structures from inhibitory regulation. The increased activity resulting may be interpreted by more rostral structures in the auditory pathway as tinnitus. Down-regulation of gamma-amino butyric acid (GABA), a major inhibitory neurotransmitter of the central auditory pathway, is a potential mechanism for the loss of inhibition. Both animal studies and human clinical trials implicate loss of inhibition, and specifically loss of GABA function, in the development of acoustic trauma-induced tinnitus.
Treat neuropathic pain PMID: 17956793 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pregabalin: its efficacy, safety and tolerability profile in generalized anxiety. Drugs Today (Barc). 2007 Sep;43(9):601-10 Authors: Owen RT Pregabalin is a structural analogue of gamma-aminobutyric acid (GABA), one of the key inhibitory neurotransmitters in the brain. Its mode of action is believed to be mediated by the alpha-2-delta-1 subunit protein of voltage-gated calcium channels to bring about its anxiolytic, anticonvulsant and antinociceptive effects. Pregabalin has linear pharmacokinetics, undergoes minimal metabolism and is excreted largely unchanged. It has a mean elimination half-life of 6.3 hours. Pregabalin's anxiolytic activity in generalized anxiety disorder has been demonstrated in seven acute randomized, double-blind, placebo-controlled trials of four to eight weeks duration, and in one six-month relapse-prevention study at doses of 150-600 mg/day using twice-daily or three-times-daily regimes. The magnitude of pregabalin's anxiolytic effects was similar to that of alprazolam, lorazepam or venlafaxine. However, pregabalin had a more consistent effect on psychic and somatic anxiety factors than the active comparators. Its speed of onset was apparent within one week - similar to the benzodiazepines, but faster than that of venlafaxine. Moreover, pregabalin's anxiolytic effect was apparent in patients with moderate or severe baseline anxiety and high or low baseline severity of sub-syndromic depression. A long-term, 26-week, open-label study showed that pregabalin's anxiolytic effects were maintained, although the fixed-dose design may have contributed to a high attrition rate. Pregabalin showed less cognitive and psychomotor impairment than alprazolam, and it showed different effects on sleep architecture to the latter in terms of REM sleep latency and slow wave stage 3/4 sleep. The most frequently reported adverse events were dizziness and somnolence, although tolerance to these developed within a few weeks. Withdrawal symptoms during a one-week taper phase were mild and were similar after both acute and chronic administration.
Treat neuropathic pain PMID: 17940637 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Duloxetine for the treatment of fibromyalgia in women: pooled results from two randomized, placebo-controlled clinical trials. J Womens Health (Larchmt). 2007 Oct;16(8):1145-56 Authors: Arnold LM, Pritchett YL, D'Souza DN, Kajdasz DK, Iyengar S, Wernicke JF BACKGROUND: To assess the efficacy (in particular, in pain, functional impairment, and quality of life) and safety and tolerability (incidence of adverse events, discontinuation rates, changes in laboratory findings, and vital signs) of duloxetine in female patients with fibromyalgia. METHODS: Data were pooled from two placebo-controlled clinical trials of similar design (randomized, 12-week, and double-blind), comparing duloxetine 60 mg a day (q.d.) or 60 mg twice daily (b.i.d.) (n = 326) with placebo (n = 212), in women who met the American College of Rheumatology criteria for primary fibromyalgia. RESULTS: Compared with the patients receiving placebo, duloxetine-treated female patients demonstrated a significantly greater improvement in the Brief Pain Inventory (BPI) average pain severity score and in the Fibromyalgia Impact Questionnaire (FIQ) total score, beginning at week 1 and continuing through week 12 (p < 0.001). Duloxetine was superior to placebo on all efficacy measures, including mean tender point threshold, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and average interference from pain scores. The duloxetine-treated group was superior to placebo on all quality of life and functional measures, including each domain of the Medical Outcomes Study Short Form-36 (SF-36). A direct treatment effect of duloxetine on pain reduction was demonstrated and shown to be independent of secondary improvement in mood (based on BPI average pain score). Significantly more duloxetine-treated patients reported treatment-emergent adverse events (296 [90.8%] duloxetine-treated and 165 [77.8%] placebo-treated, p < 0.001). Rates of serious adverse events were similar between duloxetine-treated and placebo-treated patients. CONCLUSIONS: The pooled results of these studies demonstrate that duloxetine is a safe and efficacious treatment for both the pain and functional impairment associated with fibromyalgia in female patients, while significantly improving quality of life.
Treat neuropathic pain PMID: 17937567 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Duloxetine and other antidepressants in the treatment of patients with fibromyalgia. Pain Med. 2007 Sep;8 Suppl 2:S63-74 Authors: Arnold LM OBJECTIVE: To review the use of duloxetine, a new selective serotonin and norepinephrine reuptake inhibitor (SNRI), and other antidepressants in the treatment of patients with fibromyalgia. DESIGN: Two randomized, placebo-controlled, double-blind, parallel-group, 12-week trials of duloxetine in the treatment of fibromyalgia were reviewed. Other published, randomized, placebo-controlled, double-blind trials, and meta-analyses of antidepressant treatment of fibromyalgia were identified by a PubMed search that was augmented by reference cross-check. RESULTS: Duloxetine has been shown to be an effective and safe treatment for many of the symptoms associated with fibromyalgia, particularly for women. Other selective SNRIs also show promise in the treatment of fibromyalgia. Until recently, tricyclic agents that have serotonin and norepinephrine reuptake inhibitory activity had been the most commonly studied group of antidepressants, and they are effective in treating pain and other symptoms associated with fibromyalgia, although their use may be limited by safety and tolerability concerns. There are few randomized, controlled studies of selective serotonin reuptake inhibitors in fibromyalgia, and the results have been mixed. CONCLUSIONS: Antidepressants play an important role in the treatment of patients with fibromyalgia. Agents with dual effects on serotonin and norepinephrine appear to have more consistent benefits than selective serotonin antidepressants for the treatment of persistent pain associated with fibromyalgia.
Treat neuropathic pain PMID: 17714117 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Duloxetine status. Pain Med. 2007 Sep;8 Suppl 2:S25-6 Authors: Fishbain DA
Treat neuropathic pain PMID: 17714112 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
A retrospective evaluation of the use of gabapentin and pregabalin in patients with postherpetic neuralgia in usual-care settings. Clin Ther. 2007 Aug;29(8):1655-70 Authors: Gore M, Sadosky A, Tai KS, Stacey B BACKGROUND: Both gabapentin and pregabalin are approved for the management of postherpetic neuralgia (PHN), although dosing and pharmacokinetic differences between these medications may affect their use in actual practice. OBJECTIVES: This study was conducted to characterize the use of gabapentin and pregabalin in the management of PHN in clinical practice, with a specific focus on the doses actually prescribed and changes in the use of other neuropathic pain-related medications after the initiation of gabapentin or pregabalin. METHODS: The PharMetrics Patient-Centric Database was used to identify patients with PHN who were newly prescribed gabapentin or pregabalin between September 1, 2005, and March 31, 2006. The out-comes of interest were the prevalence of comorbidities, exposure to neuropathic pain-related medications (ie, the proportions of patients receiving >or=1 prescription for these medications in the 6-month periods before and after the date of the first gabapentin or pregabalin prescription), and attainment of therapeutic dose levels (gabapentin, >or=1800 mg/d; pregabalin, >or=150 mg/d). RESULTS: The database search identified 151 patients with PHN who were newly prescribed gabapentin (57.0% female; mean [SD] age, 55.8 [11.3] years) and 100 patients who were newly prescribed pregabalin (62.0% female; mean age, 52.8 [9.4] years). The prevalence of comorbidities did not differ significantly between recipients of prescriptions for gabapentin or pregabalin, with the exception of hyperlipidemia, which was more prevalent in those prescribed gabapentin (33.8% vs 22.0%, respectively; P = 0.044), and depression, which was more prevalent in those prescribed pregabalin (12.0% vs 4.6%, respectively; P = 0.031). In the pretreatment period, those who were prescribed pregabalin had significantly greater use of long-acting opioids (P = 0.005), anticonvulsants (P < 0.001), selective norepinephrine reuptake inhibitors (P < 0.001), and the lidocaine 5% patch (P = 0.005) compared with those prescribed gabapentin. Use of any opioid increased from pretreatment to follow-up in those prescribed gabapentin, significantly so in those who received >or=2 opioid prescriptions (P = 0.016). Use of any opioid decreased significantly from pre-treatment to follow-up in those prescribed pregabalin (P = 0.005), particularly in those who received >or=2 opioid prescriptions (P = 0.004). Tramadol use decreased significantly in those prescribed gabapentin (P = 0.045), and anticonvulsant use decreased significantly in those prescribed pregabalin (P = 0.004). Among patients prescribed gabapentin or pregabalin who received 1 prescription, 2 consecutive prescriptions, and >or=3 consecutive prescriptions, a greater proportion of those prescribed pregabalin attained therapeutic dose levels by their first, second, and third consecutive prescriptions compared with those prescribed gabapentin (69.0% vs 3.5%, respectively [P < 0.001]; 71.4% vs 21.7% [P < 0.001]; and 89.3% vs 46.2% [P < 0.001], respectively). CONCLUSIONS: In these patients with PHN in the usual-care setting, opioid use increased after the initiation of gabapentin and decreased after the initiation of pregabalin. Few of those prescribed gabapentin received a prescription for a therapeutic dose, whereas a greater proportion of patients who were prescribed pregabalin received a prescription for a therapeutic dose.
Treat neuropathic pain PMID: 17919547 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Evidence for the efficacy of duloxetine in treating mild, moderate, and severe depression. Int Clin Psychopharmacol. 2007 Nov;22(6):348-55 Authors: Shelton RC, Andorn AC, Mallinckrodt CH, Wohlreich MM, Raskin J, Watkin JG, Detke MJ Clinicians need to know whether duloxetine is effective in patients across a broad range of depressive symptoms and depression severity. Data were pooled from nine randomized, double-blind, placebo-controlled studies in major depressive disorder (total N=2227) comparing duloxetine (40-120 mg/day) with placebo for 8-9 weeks. Patients were retrospectively stratified by baseline score on the HAMD17 into mild (< or =19; n=682), moderate (n=1099), or severe (> or =25; n=446) groups. Duloxetine produced significantly greater baseline-to-endpoint mean change than placebo in HAMD17 total score, Maier and retardation subscales, and the Clinical Global Impressions-Severity of Illness scale in all three cohorts. Significant improvement was seen in HAMD17 items 1 (depressed mood), 3 (suicide), 7 (work and activities), and 10 (psychic anxiety) regardless of severity. The HAMD17 anxiety subscale and items 13 (somatic symptoms-general) and 15 (hypochondriasis) showed significant improvement only in moderately and severely ill patients. Significant improvement in the HAMD17 Maier subscale was seen in all groups by week 1. In all three groups, placebo was significantly superior to duloxetine at early visits on HAMD17 item 12 (somatic symptoms-GI). Mildly and severely ill patients exhibited significant reduction in visual analog scale overall pain severity at the study endpoint. The studies contained fewer patients with very mild or very severe illness, limiting our ability to draw conclusions in these patient populations. Duloxetine demonstrated superior efficacy in the treatment of major depressive disorder, when compared with placebo, regardless of the baseline severity of depressive symptoms, although effect sizes were largest in the most severely depressed patients.
Treat neuropathic pain PMID: 17917553 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Optimization of an HPLC method for determination of gabapentin in dosage forms through derivatization with 1-fluoro-2,4-dinitrobenzene. Chem Pharm Bull (Tokyo). 2007 Oct;55(10):1427-30 Authors: Souri E, Jalalizadeh H, Shafiee A A rapid, sensitive and accurate high performance liquid chromatography with UV detection method was developed and validated for the quantification of gabapentin in dosage forms. Gabapentin was quantified after pre-column derivatization with 1-fluoro-2,4-dinitrobenzene. Amlodipine was used as an internal standard. The chromatographic separation was carried out on a Nova-Pak C(18) column using a mixture of acetonitrile-sodium dihydrogenphosphate (pH 2.5; 0.05 M) (70:30, v/v) as mobile phase with UV detection at 360 nm. The method was linear over the range of 10-500 microg/ml of gabapentin (r(2)>0.999). The within-day and between-day precision values were in the range of 0.86-1.11%. The method was successfully used for quantitative determination and dissolution rate study of Neurontin capsules.
Treat neuropathic pain PMID: 17917283 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Determination of duloxetine in human plasma by liquid chromatography with atmospheric pressure ionization-tandem mass spectrometry and its application to pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 15;858(1-2):269-75 Authors: Senthamil Selvan P, Gowda KV, Mandal U, Sam Solomon WD, Pal TK A rapid, sensitive and accurate liquid chromatographic-tandem mass spectrometry (LC-MS-MS) method is described for the determination of duloxetine in human plasma. Duloxetine was extracted from plasma using methanol and separated on a C18 column. The mobile phase consisting of a mixture of acetonitrile and 5mM ammonium acetate (45:55, v/v, pH 3.5) was delivered at a flow rate of 0.3 ml/min. Atmospheric pressure ionization (API) source was operated in positive ion mode. Multiple reaction monitoring (MRM) mode using the transitions of m/z 298.1-->m/z 44.0 and m/z 376.2-->m/z 123.2 were used to quantify duloxetine and internal standard (I.S.), respectively. The linearity was obtained over the concentration range of 0.1-50.0 ng/ml and the lower limit of quantitation (LLOQ) was 0.1 ng/ml. This method was successfully applied to pharmacokinetic study of a duloxetine formulation product after oral administration to healthy human subjects.
Treat neuropathic pain PMID: 17904920 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
The preoperative use of gabapentin, dexamethasone, and their combination in varicocele surgery: a randomized controlled trial. Anesth Analg. 2007 Oct;105(4):1137-42, table of contents Authors: Koç S, Memis D, Sut N BACKGROUND: We investigated the effects of gabapentin and dexamethasone given together or separately 1 h before the start of surgery on laryngoscopy, tracheal intubation, intraoperative hemodynamics, opioid consumption, and postoperative pain in patients undergoing varicocele operations. METHODS: Patients were randomly divided into four double-blind groups: group C (control, n = 20) received placebo, group G (gabapentin, n = 20) received 800 mg gabapentin, group D (dexamethasone, n = 20) received 8 mg dexamethasone, group GD (gabapentin plus dexamethasone) received both 800 mg gabapentin and 8 mg dexamethasone IV 1 h before the start of surgery. Standard induction and maintenance of anesthesia were accomplished and continued by propofol and remifentanil infusion. Heart rate and arterial blood pressure were recorded before induction and after intubation. Intraoperative total remifentanil consumption was recorded. Hemodynamic variables and visual analog scale were recorded for 24 h. Side effects were noted. RESULTS: Hemodynamics at 1, 3, 5, and 10 min after tracheal intubation, total remifentanil consumption during surgery, postoperative visual analog scale scores at 30 min, 1, 2, 4, 6, and 12 h, and postoperative nausea and vomiting were found to be significantly lower in group GD than in group G and group D (P < 0.05 for both), and substantially lower when compared with group C (P < 0.001). All values in group C were also higher than in groups G and D (P < 0.05). CONCLUSION: Gabapentin and dexamethasone administered together an hour before varicocele surgery results in less laryngeal and tracheal intubation response, improves postoperative analgesia, and prevents postoperative nausea and vomiting better than individual administration of each drug.
Treat neuropathic pain PMID: 17898401 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
The analgesic effects of preemptive gabapentin in patients undergoing surgery for brachial plexus injury--a preliminary study. J Neurosurg Anesthesiol. 2007 Oct;19(4):235-8 Authors: Prabhakar H, Arora R, Bithal PK, Rath GP, Dash HH There are reports indicating that gabapentin may have place in the treatment of postoperative pain. No study has evaluated the effects of gabapentin on acute, postoperative pain in patients undergoing surgery for brachial plexus injuries. In this preliminary study, we evaluated gabapentin as preemptive analgesic for intraoperative period and during the acute postoperative period at rest and during movement. Twenty consecutive adult patients undergoing surgery for brachial plexus injury were enrolled for the study. Patients randomly received either oral gabapentin 800 mg or placebo capsules 2 hours before surgery. General anesthesia was induced and maintained with propofol, at bispectral index value between 40 and 60. Intraoperative fentanyl and propofol requirements were noted. Postoperatively, all patients were alert and pain was assessed using visual analog scale (VAS) for 24 hours, both during rest and movement. Whenever VAS score was more than 50 or on patients' demand, ketorolac 30 mg was given as rescue analgesic. The demographics, duration of surgery, and propofol consumption in both groups were comparable. Intraoperative and postoperative heart rate and mean blood pressure were also comparable. Significant difference was noted in intraoperative fentanyl consumption (P=0.03), total dose of rescue analgesic (P=0.004), and VAS score at rest and movement, between the 2 groups; less in gabapentin group as compared with placebo group (P=0.01 and 0.04, at rest and movement, respectively). A single oral dose of gabapentin 800 mg, as preemptive analgesic in patients undergoing surgery for brachial plexus injury is found to be an effective adjunct to intraoperative and postoperative pain. Pain is reduced not only at rest but also during movement.
Treat neuropathic pain PMID: 17893574 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Inhibitory mechanisms of gabapentin, an antiseizure drug, on platelet aggregation. J Pharm Pharmacol. 2007 Sep;59(9):1255-61 Authors: Pan CF, Shen MY, Wu CJ, Hsiao G, Chou DS, Sheu JR Gabapentin (Neurontin) is an analogue of gamma-aminobutyric acid (GABA) that is effective against partial seizures. Gabapentin has been reported to modulate serotonin release from platelets, but the effects of gabapentin on platelet activation have not been explored. In this study, gabapentin concentration-dependently (60-240 microM) inhibited platelet aggregation in washed platelets stimulated by collagen (1 microg mL(-1)), ADP (20 microM) and arachidonic acid (60 microM). Gabapentin (120 and 240 microM) also concentration-dependently inhibited collagen (1 microg mL(-1))-induced phosphoinositide breakdown, intracellular Ca(2+) mobilization, thromboxane A(2) formation, and p38 MAPK phosphorylation in human platelets. In conclusion, the most important findings of this study suggest that gabapentin inhibits platelet aggregation, at least in part, through the phospholipase C-inositol 1,4,5-trisphosphate-thromboxane A(2)-Ca(2+) pathway. Thus, it is possible that gabapentin treatment, alone or in combination with other antiplatelet drugs, may induce or potentiate inhibition of platelet aggregation, which may affect haemostasis in-vivo.
Treat neuropathic pain PMID: 17883897 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Efficacy of duloxetine as a migraine preventive medication: possible predictors of response in a retrospective chart review. Headache. 2007 Sep;47(8):1200-3 Authors: Taylor AP, Adelman JU, Freeman MC OBJECTIVE: This case series is a retrospective chart analysis conducted to evaluate the efficacy of duloxetine as a migraine preventive medication and to suggest possible predictors of response. BACKGROUND: Duloxetine, a relatively new selective serotonin and norepinephrine reuptake inhibitor, is FDA-approved for treatment of depression and diabetic peripheral neuropathic pain. The efficacy of duloxetine as a headache preventive medication is currently unknown. METHOD: A retrospective chart review was performed using the electronic medical records of Headache Wellness Center, a headache specialty practice in Greensboro, North Carolina. From January 2004 to December 2006, 65 patients were identified who were prescribed duloxetine for migraine prevention for at least 2 months. Doses ranged from 30 mg qd to 90 mg qd. Frequency, severity, and impact of migraine disability were measured at baseline and compared to values obtained after 2 months of treatment. RESULTS: The total patient sample demonstrated a reduction in mean monthly headache frequency from 19.40 (SD=7.1) to 15.70 (SD=8.2) (P= .01). The 50% responder rate was 22%. In subset analysis, individuals with abnormal baseline Zung anxiety scores demonstrated a greater reduction in mean monthly headache frequency (4.28, P= .03) and a greater responder rate (25%) than those in the total patient sample. Non-statistically significant trends were observed in those patients with abnormal baseline Zung Depression scores exhibiting a less robust mean monthly migraine reduction (2.75, P= .18) than those with normal baseline depression scores (3.42, P= .07). CONCLUSIONS: Duloxetine demonstrates minimal effectiveness as a headache preventive medication. An interesting trend suggests that the presence of anxiety may be a positive predictor in treatment with duloxetine.
Treat neuropathic pain PMID: 17883526 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pregabalin (Lyrica) for fibromyalgia. Med Lett Drugs Ther. 2007 Sep 24;49(1270):77-8 Authors:
Treat neuropathic pain PMID: 17878888 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Cost-effectiveness analysis of pregabalin versus gabapentin in the management of neuropathic pain due to diabetic polyneuropathy or post-herpetic neuralgia. Curr Med Res Opin. 2007 Oct;23(10):2585-96 Authors: Rodríguez MJ, Díaz S, Vera-Llonch M, Dukes E, Rejas J OBJECTIVE: To estimate the cost-effectiveness of branded pregabalin (PGB) versus generic gabapentin (GBP) in patients with neuropathic pain (NeP) due to painful diabetic polyneuropathy (DPN) or post-herpetic neuralgia (PHN) in Spain. METHODS: Using stochastic simulation, we estimated the cost-effectiveness of PGB 150-600 mg/d vs. GBP 900-3600 mg/d in a hypothetical cohort of 1000 patients. The model used data from three randomized controlled clinical trials. Pain was evaluated using a 0-10 scale. Mean baseline pain was 6.9 in both treatment groups. The model assigned untreated pain scores over 84 days. Treated scores were calculated using weekly changes in pain scores from trials. Outcomes included the numbers of days with no or mild pain (score < 4), days with >or= 30% and >or= 50% reductions in pain intensity, quality-adjusted life-years (QALYs), and estimated health costs. RESULTS: Compared with GBP, PGB yielded an estimated mean of 8 (standard error, 0.4) additional days with no or mild pain, 6 (0.4) days with >or= 30% reduction in pain intensity, 9 (0.5) days with >or= 50% reduction in pain intensity, and a gain of 0.1186 (0.0002) QALYs for 12 weeks. The estimated total health costs of therapies were euro 1049 (euro 35) for PGB and euro 951 (euro 38) for GBP, respectively. Incremental cost-effectiveness ratio (ICER) for PGB versus GBP were a mean of euro 12 (95% confidence interval, euro 1-24) per additional day with no or mild pain, euro 431 (dominant-euro 876) per additional patient with no or mild pain, and euro 20 535 (euro 1607-40 345) per QALY gained. CONCLUSIONS: According with data used in this modeling in patients with NeP due to DPN and/or PHN, PGB was shown to be more cost-effective than generic gabapentin in Spain.
Treat neuropathic pain PMID: 17875242 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pregabalin in patients with antidepressant treatment-resistant somatoform disorders: a case series. J Clin Psychopharmacol. 2007 Oct;27(5):537-9 Authors: Harnack D, Scheel M, Mundt A, Kupsch A, Heinz A, Ströhle A Treat neuropathic pain PMID: 17873703 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pregabalin decreases visceral pain and prevents spinal neuronal activation in rats. Gut. 2007 Oct;56(10):1482-4 Authors: Million M, Wang L, Adelson DW, Roman F, Diop L, Taché Y Treat neuropathic pain PMID: 17872585 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3). Cancer. 2007 Nov 1;110(9):2110-8 Authors: Rao RD, Michalak JC, Sloan JA, Loprinzi CL, Soori GS, Nikcevich DA, Warner DO, Novotny P, Kutteh LA, Wong GY, BACKGROUND: The antiepileptic agent, gabapentin, has been demonstrated to relieve symptoms of peripheral neuropathy due to various etiologies. On the basis of these data, a multicenter, double-blind, placebo-controlled, crossover, randomized trial was conducted to evaluate the effect of gabapentin on symptoms of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Patients with symptomatic CIPN who complained of 'average' daily pain scores of either 1) >/=4 on a 0-10 numerical rating scale (NRS); or 2) >/=1 on the 0-3 Eastern Cooperative Oncology Group neuropathy scale (ENS) were eligible (higher numbers indicate greater severity of symptoms in both scales). Patients were randomized to receive gabapentin (target dose, 2700 mg) or placebo for 6 weeks. Crossover occurred after a 2-week washout period. CIPN-related symptoms were evaluated weekly by questionnaires. Statistical methods followed established methods for crossover designs, including Student t tests to compare average intrapatient differences between treatments and linear models to adjust for potential concomitant covariates. RESULTS: There were 115 patients who were randomly assigned to the treatment or control arm. Both groups were well matched by symptoms at study entry. Changes in symptom severity were statistically similar between the 2 groups during the study. Adverse events were mild and similar in both groups. CONCLUSIONS: This trial failed to demonstrate any benefit to using gabapentin to treat symptoms caused by CIPN. Treat neuropathic pain PMID: 17853395 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Cost-effectiveness of a lidocaine 5% medicated plaster relative to gabapentin for postherpetic neuralgia in the United Kingdom. Clin Ther. 2007 Jul;29(7):1491-507 Authors: Dakin H, Nuijten M, Liedgens H, Nautrup BP BACKGROUND: Approximately 50% of elderly patients develop postherpetic neuralgia (PHN) after herpes zoster infection (shingles). A lidocaine 5% medicated plaster marketed in the United Kingdom in January 2007 has been shown to be an effective topical treatment for PHN with minimal risk of systemic adverse effects. OBJECTIVE: This paper assessed the cost-effectiveness of using a lidocaine plaster in place of gabapentin in English primary care practice to treat those PHN patients who had insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants (TCAs). The analysis took the perspective of the National Health Service (NHS). METHODS: The costs and benefits of gabapentin and the lidocaine plaster were calculated over a 6-month time horizon using a Markov model. The model structure allowed for differences in costs, utilities, and transition probabilities between the initial 30-day run-in period and maintenance therapy and also accounted for add-in medications and drugs received by patients who discontinued therapy. Most transition probabilities were based on non-head-to-head clinical trials identified through a systematic review. Data on resource utilization, discontinuation rates, and add-in or switch medications were obtained from a Delphi panel; cost data were from official price tariffs. Published utilities were adjusted for age and were supplemented and validated by the Delphi panel. RESULTS: Six months of therapy with the lidocaine plaster cost pound 549 per patient, compared with pound 718 for gabapentin, and generated 0.05 more quality-adjusted life-years (QALYs). The lidocaine plaster therefore dominated gabapentin (95% CI, dominant- pound 2163/QALY gained). Probabilistic sensitivity analysis showed that there was a 90.15% chance that the lidocaine plaster was both less costly and more effective than gabapentin and a 99.99% chance that it cost < pound 20,000/QALY relative to gabapentin. Extensive deterministic sensitivity analyses confirmed the robustness of the conclusions. CONCLUSION: This study found that the lidocaine 5% medicated plaster was a cost-effective alternative to gabapentin for PHN patients who were intolerant to TCAs and in whom analgesics were ineffective, from the perspective of the NHS. Treat neuropathic pain PMID: 17825701 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Single-blind, placebo-controlled pilot study of pregabalin for ataxia in cortical cerebellar atrophy. Acta Neurol Scand. 2007 Oct;116(4):235-8 Authors: Gazulla J, Benavente I OBJECTIVE : To preliminarily compare the efficacy of pregabalin with that of placebo on the cerebellar signs caused by cortical cerebellar atrophy (CCA). A deficiency of gamma-aminobutyric acid (GABA) has been described in the cerebellum in CCA, and pregabalin has been shown to enhance GABA release in rat hippocampus. PATIENTS AND METHODS: Two consecutive patients with clinical diagnoses of CCA took part in the study. A placebo and pregabalin, 225 mg per day, were administered in a single-blind scheme during 15 day periods to every patient; cerebellar function was evaluated with the Scale for the Assessment and Rating of Ataxia (SARA) at the end of each period. A video recording of the SARA items performed by the first patient accompanies this article. RESULTS: Total SARA scores of 19 and 15 were obtained for the patients after placebo administration. The SARA scores decreased to 11 and 8, respectively, with the administration of pregabalin; an important amelioration of the ataxia was also evident. Both patients preferred continuing treatment with pregabalin when the trial was over. CONCLUSION: Pregabalin was superior to placebo in the improvement of the cerebellar signs caused by CCA. Further studies are needed to confirm the present results. Treat neuropathic pain PMID: 17824901 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Exploratory polysomnographic evaluation of pregabalin on sleep disturbance in patients with epilepsy. J Clin Sleep Med. 2007 Aug 15;3(5):473-8 Authors: de Haas S, Otte A, de Weerd A, van Erp G, Cohen A, van Gerven J OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. Treat neuropathic pain PMID: 17803010 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Gabapentin Extended-Release - Depomed: Gabapentin ER, Gabapentin Gastric Retention, Gabapentin GR. Drugs R D. 2007;8(5):317-20 Authors: Depomed is developing an extended-release (ER) oral formulation of gabapentin, a GABA receptor agonist commonly used for the treatment of epilepsy and seizures, neuropathic pain and hot flushes. Gabapentin ER is based on the company's proprietary AcuForm drug delivery technology, which is part of the Gastric Retention (GR) family of technologies; this offers improved drug absorption and bioavailability compared with the existing immediate-release formulation of gabapentin (Neurontin), making gabapentin ER suitable for twice-daily dosing. The product is in clinical development for the treatment of postherpetic neuralgia and diabetic neuropathies in the US. Additionally, Depomed has commenced a phase II trial of gabapentin ER in postmenopausal patients with hot flushes.Depomed's AcuForm platform is based on polymer technology that provides targeted drug delivery for a variety of compounds. Following ingestion, AcuForm tablets swell and are retained for 6-8 hours in the stomach, enabling controlled and prolonged release of gabapentin to the upper intestinal tract; this extends the time of drug delivery to the small intestine for complete and safe elimination via the lower intestinal track.Gabapentin ER is available for licensing.Depomed acquired exclusive development and commercialisation rights to gabapentin ER in September 2003 via its subsidiary, Depomed Development Ltd (DDL). Depomed is not required to pay upfront license fees, but will make royalty and milestone payments to DDL upon successful commercialisation of gabapentin ER.Gabapentin ER was originally developed by DDL, a joint venture between Depomed and Elan established in January 2000 to design products using the GR family of technologies. However, in efforts to restructure joint venture relationships, Elan withdrew from operational involvement of DDL in September 2003, and Depomed has gained full ownership of DDL. Depomed sublicensed exclusive rights to a US patent (held by the University of Rochester) covering the use of gabapentin in the treatment of hot flushes from PharmaNova in October 2006. Under the agreement, Depomed paid PharmaNova an upfront fee of US dollars 500 000. PharmaNova is also entitled to milestone payments and royalties on sales of gabapentin ER in this indication only.Depomed has reported significant safety and efficacy benefits from gabapentin ER in its phase II trial. This study was initiated in February 2005 following positive results from a phase I trial in which gabapentin ER demonstrated a pharmacokinetic profile suitable for twice-daily dosing. In two pharmacokinetic studies, gabapentin ER achieved improved bioavailability at higher doses. This result supports Depomed's development of a once- or twice-daily product with potentially fewer adverse events.The basic US patents relating to gabapentin expired in 2000. Depomed holds exclusive rights to a US patent (No. 6 310 098) held by the University of Rochester covering the use of gabapentin to treat hot flushes.Additionally, Depomed was issued a US patent (No. 6 723 340) in May 2004 that covers proprietary polymer combinations (as used in AcuForm tablets) to create improved formulations of existing drugs. Treat neuropathic pain PMID: 17767396 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
The effect of duloxetine on primary pain symptoms in Parkinson disease. Clin Neuropharmacol. 2007 Jul-Aug;30(4):201-5 Authors: Djaldetti R, Yust-Katz S, Kolianov V, Melamed E, Dabby R OBJECTIVES: To study the effect of duloxetine (Cymbalta), a selective serotonin and norepinephrine reuptake inhibitor, on pain symptoms in Parkinson Disease (PD). METHODS/PATIENTS: Twenty-three patients with PD with painful phenomena were treated with duloxetine for 6 weeks in an open-label design. Assessments were performed before and at treatment completion and consisted of a Visual Analogue Scale, the Brief Pain Inventory, Short-Form McGill Pain Questionnaire, Parkinson Disease Quality of Life Questionnaire-39-item version, and motor part of the Unified Parkinson Disease Rating Scale. Pain threshold was assessed by quantitative sensory tests. RESULTS: Thirteen of the 20 patients who completed the study reported varying degrees of pain relief. The mean Visual Analogue Scale, Brief Pain Inventory, and Short-Form McGill Pain Questionnaire scores decreased significantly. There was no change in pain threshold after treatment. CONCLUSIONS: Duloxetine seems to be effective for the treatment of central pain in PD. Treat neuropathic pain PMID: 17762316 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Duloxetine in the treatment of major depressive disorder: an open-label study. BMC Psychiatry. 2007;7:43 Authors: Hudson JI, Perahia DG, Gilaberte I, Wang F, Watkin JG, Detke MJ BACKGROUND: Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined. METHODS: Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17) total score >or=18 and a Clinical Global Impression of Severity (CGI-S) score >or=4 at baseline. Efficacy measures included the HAMD17 total score, HAMD17 subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale. RESULTS: The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by >or=10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD17, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment. CONCLUSION: In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD. Treat neuropathic pain PMID: 17725843 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Effect of gabapentin on oculomotor control and parkinsonism in patients with progressive supranuclear palsy. Eur J Neurol. 2007 Sep;14(9):1060-2 Authors: Poujois A, Vidailhet M, Trocello JM, Bourdain F, Gaymard B, Rivaud-Péchoux S The efficacy of gabapentin on motor, oculomotor and frontal lobe symptoms was evaluated in patients with progressive supranuclear palsy (PSP) in a pilot study. Fourteen patients were included and seven of them received gabapentin. Clinical evaluation and horizontal eye movement recordings were performed at inclusion and 5-weeks later. Motor score and saccade latency in the visually guided saccade (VGS) task were identical in the two groups. However, the error rate in the antisaccade task was significantly decreased in the gabapentin group. This preliminary study shows that gabapentin improves reflexive saccade inhibition in patients with PSP but does not improve the latency of VGSs. Treat neuropathic pain PMID: 17718702 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pregabalin-induced remission in a 62-year-old woman with a 20-year history of vulvodynia. Pain Res Manag. 2007;12(3):212-4 Authors: Jerome L A case of a 62-year-old woman presenting with a 20-year history of vulvodynia previously unresponsive to medical treatment is described. The epidemiology, phenomenology and medical management of vulvodynia is reviewed. The case presentation illustrates the role of pregabalin in successful medical management of this chronic pain disorder, as well as the management of common psychiatric morbidities associated with this condition. Treat neuropathic pain PMID: 17717613 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
An open-label 52-week clinical extension comparing duloxetine with routine care in patients with diabetic peripheral neuropathic pain. Pain Med. 2007 Sep;8(6):503-13 Authors: Wernicke JF, Wang F, Pritchett YL, Smith TR, Raskin J, D'Souza DN, Iyengar S, Chappell AS OBJECTIVE: To assess the safety of duloxetine at a fixed-dose of 60 mg twice daily (BID) for up to 52 weeks, and compare duloxetine with routine care in the management of patients with diabetic peripheral neuropathic pain (DPNP). DESIGN AND INTERVENTIONS: Patients who completed a 13-week, randomized, double-blind, placebo-controlled acute therapy period were randomly reassigned in a 2:1 ratio to therapy with duloxetine 60 mg BID (N = 197) or routine care (N = 96) for an additional 52 weeks. PATIENTS: The trial included outpatients > or =18 years of age diagnosed with moderate to severe DPNP caused by type 1 or type 2 diabetes. RESULTS: Fourteen patients discontinued due to adverse events or death (11 [5.6%] duloxetine- and 3 [3.1%] routine care-treated patients). There were no significant therapy-group differences observed for patients with >/=1 serious adverse event. In total, 110 (55.8%) duloxetine- and 47 (49%) routine care-treated patients had > or =1 treatment-emergent adverse event (TEAE). The TEAE with a significant therapy-group difference, with patients in the duloxetine therapy group experiencing a higher percentage of events, was asthenia (11 [5.6%] duloxetine- vs no routine care-treated patients). Duloxetine did not appear to adversely affect lipid profiles, or nerve or eye function. There were no significant therapy-group differences observed in mean change in systolic blood pressure, weight, or electrocardiogram parameters. Significant therapy-group differences were observed in favor of duloxetine in the SF-36 physical component summary score, and subscale scores of physical functioning, bodily pain, mental health, and vitality. CONCLUSIONS: The results of this study provide support for the use of duloxetine in the long-term management of DPNP.
Treat neuropathic pain PMID: 17716324 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pharmacokinetics and tolerability of duloxetine following oral administration to healthy Chinese subjects. Clin Pharmacokinet. 2007;46(9):767-75 Authors: Tianmei S, Knadler MP, Lim MT, Yeo KP, Teng L, Liang S, Pan AX, Lobo ED OBJECTIVES: The objectives of the study were to characterise the pharmacokinetics and assess the tolerability of duloxetine in healthy Chinese subjects after single and multiple oral 60 mg dosing. METHODS: This was a single-centre, double-blind, randomised, placebo-controlled, single-period study in healthy native Chinese subjects. A total of 32 subjects, 19 men (14 on duloxetine, 5 on placebo) and 13 women (10 on duloxetine, 3 on placebo) between the ages of 20 and 39 years, participated in the study. Duloxetine 60 mg (enteric-coated pellets in a capsule) was given orally once on day 1 and once daily on days 4 to 9. Sequential blood samples were collected over 72 hours after the dose on days 1 and 9, and a predose sample was obtained on days 7 and 8. Duloxetine concentrations in plasma were determined by a validated liquid chromatography-tandem mass spectrometry method. The tolerability evaluation included a physical examination, vital signs, adverse event monitoring and clinical laboratory evaluations. RESULTS: Duloxetine disposition on oral administration is characterised by a one-compartment pharmacokinetic model. Duloxetine is well absorbed, with a median time of maximum plasma concentration at 6 and 4 hours following single and multiple dosing, respectively. At steady state, the mean apparent oral clearance (CL(ss)/F), mean apparent volume of distribution (V(ss)/F) and mean terminal elimination half-life (t((1/2))) were 86.8 L/h, 1570L and 11 hours, respectively. CL/F and V(ss)/F on single dosing were not statistically significantly different (p > 0.05) compared with multiple dosing. The linearity index, calculated as the ratio of the area under the plasma concentration-time curve (AUC) during the dosing interval tau at steady state (AUC(tau)(,ss)) to the AUC from time zero to infinity after single dosing (AUC(infinity,single dose)) was 1.15 (coefficient of variation 35.7%). The accumulation in duloxetine exposure was estimated to be 50% on multiple dosing compared with single dosing, consistent with the t((1/2)) and dosing interval (24 hours). The pharmacokinetic parameters of duloxetine in Chinese subjects were not statistically significantly different from those reported previously in Caucasian and Japanese subjects. There were no clinically significant adverse events, abnormal safety laboratory data or vital sign changes reported. CONCLUSION: Duloxetine pharmacokinetics in healthy Chinese subjects given a 60 mg once-daily dosing regimen were well characterised and consistent with known duloxetine pharmacokinetics in healthy Caucasian and Japanese subjects. Both single dosing and multiple once-daily dosing of duloxetine 60 mg were well tolerated by healthy Chinese subjects in this study.
Treat neuropathic pain PMID: 17713974 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials. Pharmacopsychiatry. 2007 Jul;40(4):163-8 Authors: Bech P BACKGROUND: Pregabalin has been evaluated in randomised clinical trials in patients with generalised anxiety disorder (GAD) in a fixed-dose design and with the Hamilton Anxiety Scale (HAM-A) as outcome measure. Four of the available six placebo-controlled trials were found acceptable for a pooled analysis of dose-response relationship. METHOD: Both the full HAM-A (14) and the six-item subscale covering the core items of GAD (HAM-A (6)) were analysed. The unbiased effect size statistic was used to evaluate the advantage of pregabalin over placebo. An effect size of 0.40 or higher was used to indicate a clinically significant effect. RESULTS: Four placebo-controlled trials running over four weeks and covering the dose range from 150 mg to 600 mg pregabalin were sufficiently homogeneous to be pooled for the analysis. Both HAM-A (6) and HAM-A (14) showed that for the dose of 150 mg pregabalin daily the effect size was clearly below 0.40. For the dose range of 200-450 mg daily, the effect sizes exceeded 0.40, with a plateau-like curve. The maximum dose of 600 mg daily did not increase effect size. On the HAM-A (14) as well as the item of sleep, effect size was generally higher, but followed the same pattern as the HAM-A (6). DISCUSSION: The dose of 150 mg pregabalin over the four weeks of the trials was found insufficient for the treatment of GAD. In the dose range of 200-450 mg daily, a clinically significant effect was obtained, although with a plateau-like curve which was not increased for the maximum dose of 600 mg daily.
Treat neuropathic pain PMID: 17694480 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Low-dose gabapentin in treatment of high-altitude headache. Cephalalgia. 2007 Nov;27(11):1274-7 Authors: Jafarian S, Gorouhi F, Salimi S, Lotfi J Headache is the most prevalent symptom of acute mountain sickness. We conducted a pilot clinical trial at an altitude of 3500 m to evaluate the efficacy of gabapentin in treatment of high-altitude headache (HAH). Twenty-four adult HAH patients (10 female, 14 male; age 18-50 years) were randomly assigned to receive either 300 mg of gabapentin capsule or identical placebo. After 1 h the presence of HAH and need to receive supplementary analgesic were assessed. The duration of the HAH-free phase after taking additional analgesic was also registered. Four patients in the gabapentin group asked for additional analgesics, whereas nine placebo recipients did not find primary medication satisfactory after the first hour of treatment (P = 0.04). The mean HAH-free period was 17.10 h in the gabapentin group, which was significantly higher than in the placebo group with a mean of 10.08 h (P = 0.02). This preliminary observation indicates that gabapentin is effective in treatment and alleviation of HAH.
Treat neuropathic pain PMID: 17692105 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Gabapentin: a promising drug for the treatment of uremic pruritus. Saudi J Kidney Dis Transpl. 2007 Sep;18(3):378-81 Authors: Naini AE, Harandi AA, Khanbabapour S, Shahidi S, Seirafiyan S, Mohseni M Despite advances made in treatment, uremic pruritus remains a common and distressing symptom in patients on hemodialysis (HD). Gabapentin is an effective drug in the management of neuropathic pain. Considering that neuropathic pain and pruritus share similar pathogenic mechanisms, we conducted this study to evaluate the efficacy of gabapentin in controlling uremic itch. In a double blind, placebo-controlled trial, 34 adult patients on maintenance HD were enrolled. The patients were assigned to receive four weeks of treatment with either gabapentin (400 mg) or placebo administered twice weekly after HD sessions. Pruritus scores were measured using a visual analogue scale and compared between the two groups.After four weeks of treatment, the mean decrease in pruritus score in gabapentin and placebo groups was 6.7 +/- 2.6 and 1.5 +/- 1.8, respectively (p< 0.001). None of the patients was forced to drop out of the study due to side effects of the treatment. Our study suggests that gabapentin is a safe and effective treatment for uremic itch.
Treat neuropathic pain PMID: 17679749 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
A cost-effectiveness comparison of desipramine, gabapentin, and pregabalin for treating postherpetic neuralgia. J Am Geriatr Soc. 2007 Aug;55(8):1176-84 Authors: O'Connor AB, Noyes K, Holloway RG OBJECTIVES: To compare the net health effects and costs resulting from treatment with different first-line postherpetic neuralgia (PHN) medications. DESIGN: Cost-utility analysis using published literature. PARTICIPANTS: Hypothetical cohort of patients aged 60 to 80 with PHN. INTERVENTIONS: Desipramine 100 mg/d, gabapentin 1,800 mg/d, and pregabalin 450 mg/d. MEASUREMENTS: A decision model was designed to describe possible treatment outcomes, including different combinations of analgesia and side effects, during the first 3 months of therapy for moderate to severe PHN. The main outcome was cost per quality-adjusted life-year (QALY) gained. Costs were estimated using the perspective of a third-party payer. Multivariate, univariate, and probabilistic sensitivity analyses were performed, and the time frame of the model was varied to 1-month and 6-month horizons. RESULTS: Desipramine was more effective and less expensive than gabapentin or pregabalin (dominant) under all conditions tested. Gabapentin was more effective than pregabalin but at an incremental cost of $216,000/QALY. Below $140/month, gabapentin became more cost-effective than pregabalin at a threshold of $50,000/QALY, and below $115/month gabapentin dominated pregabalin. CONCLUSION: Desipramine appears to be more effective and less expensive than gabapentin or pregabalin for the treatment of older patients with PHN in whom it is not contraindicated. After its price falls, generic gabapentin will likely be more cost-effective than pregabalin.
Treat neuropathic pain PMID: 17661955 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Duloxetine for the management of diabetic peripheral neuropathic pain: evaluation of functional outcomes. Pain Med. 2007 Jul-Aug;8(5):410-8 Authors: Armstrong DG, Chappell AS, Le TK, Kajdasz DK, Backonja M, D'Souza DN, Russell JM OBJECTIVE: To assess the effectiveness of duloxetine, compared with placebo, on patient-reported health outcomes over a 12-week period, in the management of diabetic peripheral neuropathic pain (DPNP). METHODS: The results were pooled from three 12-week multicenter, double-blind studies. In study 1 (N = 457), patients with DPNP were randomly assigned to treatment with duloxetine 20 mg once daily (QD), 60 mg QD, 60 mg twice daily (BID), or placebo. In studies 2 (N = 334) and 3 (N = 348), patients with DPNP were randomly assigned to treatment with duloxetine 60 mg QD, 60 mg BID, or placebo. Patient-reported functional outcomes were measured by the Short Form 36 (SF-36), the interference portion of the Brief Pain Inventory (BPI), and EuroQol 5D Health Questionnaire (EQ-5D). Results for all functional outcomes from the intent-to-treat and completer populations are discussed. RESULTS: In the SF-36 health survey and the BPI interference, duloxetine 60 mg QD and 60 mg BID were significantly superior to placebo in all the domains (P <or= 0.03). In the analysis of the EQ-5D, duloxetine 60 mg QD (P = 0.004) and 60 mg BID (P < 0.001) were significantly better than placebo on all items. CONCLUSIONS: Acute treatment with duloxetine was associated with significant improvement in functional outcomes in persons with DPNP.
Treat neuropathic pain PMID: 17661854 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Duloxetine for the management of diabetic peripheral neuropathic pain: response profile. Pain Med. 2007 Jul-Aug;8(5):397-409 Authors: Pritchett YL, McCarberg BH, Watkin JG, Robinson MJ OBJECTIVE: The current analysis examines the response profile in patients receiving duloxetine for the management of diabetic peripheral neuropathic pain (DPNP). PATIENTS/DESIGN: Data were pooled from three double-blind, randomized, placebo-controlled 12-week acute therapy trials of patients with DPNP of at least 6 months' duration. Study 1 (N = 457) had treatment groups of duloxetine 20 mg once daily (QD), 60 mg QD, 60 mg twice daily (BID), and placebo; Studies 2 (N = 334) and 3 (N = 348) compared duloxetine 60 mg QD and 60 mg BID with placebo. The primary efficacy measure in each study was the weekly mean score of the 24-hour average pain severity. Treatment response was defined as a 30% reduction in pain severity, although some analyses were repeated using alternative response criteria (50% reduction, or 2-point reduction, in pain severity). RESULTS: Consistently across the three studies, response rates at endpoint were significantly higher among patients receiving duloxetine (60 mg QD or 60 mg BID) than among those receiving placebo, regardless of the chosen response criterion (30% reduction, 50% reduction, or 2-point reduction in weekly mean of 24-hour average pain severity). The proportion of patients achieving pain relief in the duloxetine treatment groups was significantly greater than that in the placebo group at Week 1 and at all subsequent study visits to the end of acute phase therapy. Using diary data (24-hour average pain severity) from the first 7 days of treatment, the first significant separation from placebo in pain severity reduction for duloxetine 60 mg QD occurred at Day 1 (Study 1), Day 2 (Study 2), and Day 4 (Study 3), while significant separation in response rates first occurred at Day 3 when using pooled data. CONCLUSIONS: Patients with DPNP receiving duloxetine 60 mg QD or 60 mg BID had significantly higher rates of treatment response, when compared with patients receiving placebo, regardless of the chosen response criterion. Response to duloxetine treatment tended to occur early in therapy.
Treat neuropathic pain PMID: 17661853 [PubMed - indexed for MEDLINE ( Treat neuropathic pain ) ]
Pre-emptive gabapentin significantly reduces postoperative pain and morphine demand following lower extremity orthopaedic surgery. Singapore Med J. 2007 Aug;48(8):748-51 Authors: Montazeri K, Kashefi P, Honarmand A INTRODUCTION: Gabapentin has demonstrated analgesic effects in clinical trials as a preemptive analgesic and in acute postoperati |
