pregabalin and Sleep-Wake-Disorders

This meta-analysis aimed to illustrate the efficacy and safety of preganalin for pain management in patients with postherpetic neuralgia (PHN).. In July 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients with PHN that compared pregabalin versus placebo were retrieved. The endpoints were the visual analog scale (VAS) at 8 weeks, the percentage of 30% and 50% pain responders; sleep interference score and improvement in patient global impression of change (PGIC). After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary.. Seven clinical studies with 2192 patients (pregabalin group = 1381, control group = 811) were finally included in the meta-analysis. Pregabalin was associated with reduced pain scores at 8 weeks, corresponding to a reduction of 11.23 points (95% CI, -14.33, -8.13, P = .000) on a 100-point VAS. Pregabalin was also associated with a more percentage of 30% and 50% pain responders than controls (P < .05). Meanwhile, pregabalin can decrease sleep interference score and improvement in PGIC than control groups (P < .05).. Pregabalin was efficacious in the reduction of postoperative pain and improvement the sleep quality in patients with PHN.

Topics: Analgesics; Humans; Neuralgia, Postherpetic; Pregabalin; Sleep Wake Disorders; Visual Analog Scale

In 2 large-scale, placebo-controlled trials, pregabalin improved both pain and pain-related sleep interference in patients with neuropathic pain due to spinal cord injury (SCI). In both trials, pregabalin found statistically significant improvement compared with placebo after 1 week of treatment. However, the effects of pregabalin in the days immediately after initiation of treatment are unknown. The purpose of the present analysis was to determine timing of pregabalin's therapeutic effect in the days after initiation of treatment.. Data were derived from 2 trials of pregabalin in patients with SCI-related neuropathic pain. Each day patients rated severity of pain and pain-related sleep interference over the past 24 hours on a scale from 0 to 10, with higher scores indicating greater severity. To quantify timing of therapeutic effect, we compared (pregabalin [vs] placebo) daily average pain and pain-related sleep interference scores over the first 14 days of treatment. Significant improvement was defined as the first day, of ≥2 consecutive days, that pregabalin significantly (P < 0.05) reduced mean scores compared with placebo. To further quantify timing of therapeutic effect, each treatment group was examined to determine the time required to achieve a ≥1-point improvement in pain and pain-related sleep interference score among patients with a clinically meaningful and sustained response (≥30% improvement from baseline to end point) by using a time-to-event analysis method. Kaplan-Meier analyses were used to estimate the median (or 25th quartile) time (in days) required to achieve a ≥1-point improvement, among these responders, in pain and pain-related sleep interference scores. Comparisons between pregabalin and placebo were made with a log-rank test.. In both trials, significant improvement of pain and pain-related sleep interference occurred within 2 days of initiating treatment with pregabalin. Among patients reporting a clinically meaningful and sustained response to treatment (patients with ≥30% improvement from baseline to end point), the time to a ≥1-point improvement of pain and pain-related sleep interference occurred significantly earlier among pregabalin-treated patients than among placebo-treated patients. Finally, the timing of pregabalin's effect on pain and pain-related sleep interference was unaffected by the use of concomitant medications that were allowed for treatment of neuropathic pain in both trials.. Treatment with pregabalin results in rapid time to significant improvement in both pain and pain-related sleep interference in patients with neuropathic pain due to SCI. These findings should only be used as a guide to physicians and patients as to when clinical response to pregabalin may be expected.

Topics: Adult; Aged; Analgesics, Non-Narcotic; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neuralgia; Pain Measurement; Pregabalin; Randomized Controlled Trials as Topic; Retrospective Studies; Sleep Wake Disorders; Spinal Cord Injuries; Treatment Outcome

Pregabalin is approved for the treatment of a variety of clinical conditions and its analgesic, anxiolytic and anticonvulsant properties are well documented. Pregabalin's effects on sleep, however, are less well known. This review summarizes the published data on the effects of pregabalin on sleep disturbance associated with neuropathic pain, fibromyalgia, restless legs syndrome, partial onset seizures and general anxiety disorder. The data demonstrate that pregabalin has a positive benefit on sleep disturbance associated with several different clinical conditions. Polysomnographic data reveal that pregabalin primarily affects sleep maintenance. The evidence indicates that pregabalin has a direct effect on sleep that is distinct from its analgesic, anxiolytic and anticonvulsant effects.

Topics: Analgesics; Anti-Anxiety Agents; Anticonvulsants; Anxiety Disorders; Epilepsies, Partial; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Neuralgia; Polysomnography; Pregabalin; Restless Legs Syndrome; Sleep Wake Disorders; Treatment Outcome

In patients with chronic pain due to diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN), pregabalin treatment results in pain relief and improved patient function/quality of life (QoL). Few studies, however, have examined the exact relationship between pain relief and improvements in patient function/QoL. It is unclear, for example, whether pregabalin has a direct independent effect on patient function/QoL or whether improvements in function/QoL are an indirect consequent of pain relief.. To determine whether improvements in function/QoL in response to pregabalin treatment are related to the extent of pain relief in patients with neuropathic pain due to DPN or PHN and to determine whether pregabalin has a direct independent effect on patient function/QoL that is distinct from its effects on pain.. Data from 11 randomized, double-blind, placebo-controlled trials of pregabalin for the treatment of DPN or PHN were pooled for this analysis. Changes in patient function/QoL scores were plotted according to the extent of pain relief to assess whether greater levels of pain relief were associated with greater improvement in function/QoL. A novel mediation analysis was used to asses to what extent the effects of pregabalin on function/QoL scores are a direct treatment effect as opposed to an indirect effect mediated through improvements in pain or sleep.. Moderate-to-substantial pain relief (a ≥30% decrease in pain) in response to pregabalin treatment was associated with significant (P < 0.05) improvements in 36-Item Short Form Health Survey (SF-36) scores (used to assess patient function/QoL). In many patients, greatest improvement in SF-36 scores was reported by patients achieving ≥50% decrease in pain. Analysis of Patient Global Impression of Change scores revealed a similar trend, where >80% of patients who achieved substantial pain relief also reported their status as much or very much improved. A substantial direct pregabalin treatment effect was evident for many SF-36 domains that could not be explained by pain relief or improvement in sleep.. In patients with chronic pain due to DPN or PHN, improvements in patient function/QoL in response to pregabalin treatment are correlated with the extent of pain relief. However, such improvements in function/QoL are not mediated entirely through pain relief but are the result of a combination of pregabalin's effects on pain and sleep disturbance and a direct effect on patient function itself.

Topics: Analgesics; Diabetic Neuropathies; gamma-Aminobutyric Acid; Health Surveys; Humans; Neuralgia, Postherpetic; Pregabalin; Quality of Life; Randomized Controlled Trials as Topic; Sleep Wake Disorders; Treatment Outcome

Sleep disturbance is a cardinal symptom in both DSM-IV and ICD-10 criteria for generalized anxiety disorder (GAD). This review summarizes the results of clinical trials and pooled analyses that provide data on pregabalin's effect on sleep disturbance in patients diagnosed with GAD. The hypothesized mechanism of action of pregabalin is distinctly different from other anxiolytics. Pregabalin binds to a membrane α2δ subunit protein to inhibit release in excited central nervous system neurons of neurotransmitters implicated in pathological anxiety. Treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across seven placebo-controlled clinical trials. Treatment with pregabalin is associated with improvement in all forms of insomnia and improvement in sleep has been found to be correlated with reduction in functional impairment and improvement in quality of life on subjective global measures. Results of a mediational analysis suggest that 53% of the effect of pregabalin on sleep disturbance was due to a direct effect and 47% was due to an indirect effect, mediated through prior reduction in anxiety symptom severity. In patients with GAD, improvement in sleep has been found to be associated with a reduction in daytime sleepiness. However, dose-related sedation is reported, typically in the first 2 wk of treatment, in approximately 10-30% of patients, depending on the dose used and the speed of titration. Insomnia is a common component of the clinical presentation of GAD and pregabalin appears to be an efficacious treatment for this often chronic and disabling symptom.

Topics: Animals; Anxiety Disorders; Clinical Trials as Topic; gamma-Aminobutyric Acid; Humans; Pregabalin; Sleep; Sleep Wake Disorders; Treatment Outcome

There have been substantial advances in the pharmacotherapy of fibromyalgia (FM), which have occurred in parallel with advances in our understanding of the pathophysiology of FM in the past several years. Consortia of researchers have established a core set of symptom domains, which constitute the condition of FM, including pain, fatigue, sleep and mood disturbance and cognitive dysfunction, which significantly impact a patient's overall well-being and ability to function. Outcome measures, which assess these domains, both singly and in composite format, are showing increasing reliability to discriminate between the treatment and placebo arms in clinical trials of emerging therapies, which are targeting the pathophysiologic mechanisms of FM. Several different medications, including the serotonin and norepinephrine reuptake inhibitors, duloxetine and milnacipran, and the α(2)δ modulator, pregabalin, have been approved by the Food and Drug Administration (FDA) for the management of FM, based on their clinically meaningful and durable effect on pain in monotherapy trials. They also have been shown to beneficially effect patient global impression of change, function and variably other key symptom domains, such as fatigue, sleep disturbance and cognition. Other medicines, although they have not gone through the formal approval process, have also shown efficacy in multiple domains of FM. Although combination trials have generally not yet been performed, the combined use of medicines with complementary mechanisms of action is rational, and, when done with appropriate caution, will likely be shown to be safe and well tolerated. Adjunctive therapy with medicines targeted at specific symptom domains, such as sleep, as well as treatments aimed at common co-morbid conditions, such as irritable bowel syndrome, or disease states, such as rheumatoid arthritis, should be considered for the purpose of reducing the patient's overall symptom burden. Current therapies neither completely treat FM symptoms nor benefit all patients; thus, further research on new therapies with different mechanisms and side-effect profiles is needed.

Topics: Analgesics; Chronic Pain; Clinical Trials as Topic; Cognition Disorders; Cyclopropanes; Duloxetine Hydrochloride; Fatigue; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Milnacipran; Mood Disorders; Pain Management; Pregabalin; Selective Serotonin Reuptake Inhibitors; Sleep Wake Disorders; Syndrome; Thiophenes; Treatment Outcome

Chronic pain in fibromyalgia patients, together with its associated symptoms and co-morbidities, is now considered a result of dysregulated mechanisms in the central nervous system (CNS). As fibromyalgia patients often report sleep problems, the physiological processes that normally regulate sleep may be disturbed and overlap with other CNS dysfunctions. Although the mechanisms potentially linking chronic widespread pain, sleep alterations and mood disorders have not yet been proven, polysomnography findings in patients with fibromyalgia and non-restorative sleep and their relationships with clinical symptoms support the hypothesis of a conceptual common mechanism called 'central sensitisation'. Food and Drug Administration (FDA)-approved drugs for the treatment of fibromyalgia may benefit sleep, but their label does not include the treatment of fibromyalgia-associated sleep disorders. Non-pharmacological therapies (including a thorough sleep assessment) can be considered in the first-line treatment of non-restorative sleep, although they have not yet been fully investigated in patients with fibromyalgia. Both pharmacological and non-pharmacological treatments should be used cautiously in patients with fibromyalgia, bearing in mind the patients' underlying disorders and the potential interactions of the therapies.

Topics: Analgesics; Central Nervous System Sensitization; Chronic Pain; Cyclopropanes; Duloxetine Hydrochloride; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Milnacipran; Physical Therapy Modalities; Polysomnography; Pregabalin; Selective Serotonin Reuptake Inhibitors; Sleep; Sleep Wake Disorders; Syndrome; Thiophenes

Postherpetic neuralgia and painful diabetic peripheral neuropathy are common chronic neuropathic pain conditions associated with sleep disturbances. Pregabalin is indicated in the treatment of neuropathic pain. The objective of this review is to summarize the efficacy and safety of pregabalin in painful diabetic peripheral neuropathy and postherpetic neuralgia and the effect of pregabalin on sleep interference in these patients.. MEDLINE and ISI Web of Knowledge databases were searched for randomized double-blind, placebo-controlled clinical trials of pregabalin reporting sleep measures in addition to pain endpoints in patients with painful diabetic peripheral neuropathy and postherpetic neuralgia published from inception through March 2009.. Nine trials met the inclusion criteria, providing data for a total of 2399 patients with painful diabetic peripheral neuropathy or postherpetic neuralgia treated twice or three times per day with pregabalin (75-600 mg/day) or placebo on a fixed or flexible schedule. Interpretation of sleep outcomes in two studies may be limited by trial inclusion criteria which permitted benzodiazepines for sleep problems. Also, none of the studies reported objective sleep measures. Pregabalin was well tolerated. Pregabalin (150-600 mg/day) significantly reduced pain and improved pain-related sleep interference.. In addition to an analgesic benefit, pregabalin may decrease pain-related sleep interference in patients with painful diabetic peripheral neuropathy and postherpetic neuralgia.

Topics: Analgesics; Diabetic Neuropathies; Double-Blind Method; gamma-Aminobutyric Acid; Humans; Neuralgia, Postherpetic; Pain Measurement; Placebos; Pregabalin; Randomized Controlled Trials as Topic; Sleep; Sleep Wake Disorders; Treatment Outcome

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and accompanied by a variety of other symptoms such as fatigue, sleep dysfunction, depression, anxiety and cognitive disturbance. Current guidelines recommend tricyclic antidepressants or SSRIs (selective serotonin reuptake inhibitors) as first-line therapies to treat the multiple symptom domains. Until recently, however, there were no licensing authority approved treatments for FMS. The alfa 2 delta modulator pregabalin has anxiolytic, anticonvulsant and antinociceptive properties which has prompted its investigation in FMS. In a series of short-term randomized, double-blind, placebo-controlled trials of 8-14 weeks duration, pregabalin proved effective in reducing the pain and accompanying symptoms of FMS and improved quality of life domains. A 6-month double-blind, placebo-controlled trial demonstrated the durability of its effects on pain and a variety of secondary measures such as fatigue and sleep disturbance. Overall, pregabalin was well tolerated with no new adverse events emerging that have not been reported with its use in other indications.

Topics: Anticonvulsants; Anxiety Disorders; Cognition Disorders; Depression; Fatigue; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Quality of Life; Sleep Wake Disorders; Syndrome

To investigate the effect of pregabalin on wake and sleep bout parameters.. A post hoc analysis of polysomnography data from a randomized, placebo-controlled, crossover study investigating the effect of pregabalin (150 to 450 mg/d) and placebo on sleep in fibromyalgia (FM). Eligible patients had FM and sleep-maintenance problems, including wake after sleep onset ≥45 minutes and total sleep time (TST) 3.0 to 6.5 hours, but no other sleep/circadian rhythm disorders. Polysomnography was performed for 2 consecutive nights (screening, post-treatment). Wake and sleep bout duration and frequency were derived; a "bout"=consecutive 30-s epochs of sleep or wake.. Of 119 patients randomized (103 [87%] female), data were available for 103 treated with pregabalin and 106 with placebo. Pregabalin versus placebo treatment decreased mean±SD number of wake/sleep bouts (33.24±1.33 vs. 36.85±1.32; difference: -3.61 [95% confidence interval, -6.03, -1.18]; P=0.0039) and increased sleep bout duration (15.25±0.63 vs. 11.58±0.62 min; +3.67 min [2.22, 5.12 min]; P<0.0001). Pregabalin decreased mean duration of wake bouts versus placebo (3.41±0.55 vs. 3.94±0.55 min; -0.53 min [-1.06, -0.002 min]; P=0.0493). An exploratory correlation analysis of treatment effects found stage 1 sleep was negatively correlated with wake and sleep bout duration and positively with wake/sleep bout number; slow wave sleep (%total sleep time) was positively correlated with wake and sleep bout duration and negatively with wake/sleep bout number.. Pregabalin improved sleep parameters characteristic of disturbed sleep in FM, by preventing awakenings and increasing sleep bout duration. These effects are reflected in, and correlated with, a decrease in "light sleep" (stage 1) and an increase in "deep sleep" (slow wave sleep).

Topics: Analgesics; Cross-Over Studies; Female; Fibromyalgia; Humans; International Cooperation; Male; Polysomnography; Pregabalin; Single-Blind Method; Sleep Wake Disorders; Statistics as Topic

To compare pregabalin versus placebo and pramipexole for reducing restless legs syndrome (RLS)-related sleep disturbance.. Randomized, double-blinded, crossover trial.. Twenty-three US sleep centers.. Eighty-five individuals with moderate to severe idiopathic RLS and associated sleep disturbance.. Participants were randomized across 6 treatment sequences comprising three 4-week periods on pregabalin 300 mg/day (n = 75), pramipexole 0.5 mg/day (n = 76), or placebo (n = 73).. Polysomnography was conducted over 2 nights at the end of each period. Primary (wake after sleep onset [WASO], pregabalin vs placebo) and key secondary endpoints were analyzed for statistical significance, with descriptive statistics for other endpoints. Pregabalin improved sleep maintenance, demonstrated by reductions in WASO (-27.1 min vs placebo [P < 0.0001]; -26.9 vs pramipexole) and number of awakenings after sleep onset (-2.7 vs placebo; -7.9 vs pramipexole [P < 0.0001]) by polysomnography, and an increase in subjective total sleep time (30.8 min vs placebo [P < 0.0001]; 26.8 vs pramipexole). Pregabalin also increased slow wave sleep duration (20.9 min vs placebo; 32.1 vs pramipexole [P < 0.0001]). Reduction in periodic limb movement arousal index (PLMAI) with pregabalin was similar to pramipexole and greater than placebo (-3.7 PLMA/h [P < 0.0001]), although reduction in total PLM in sleep was less than for pramipexole.. This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole.. ClinicalTrials.gov identifier, NCT00991276; http://clinicaltrials.gov/show/NCT00991276.

Topics: Adolescent; Adult; Aged; Arousal; Benzothiazoles; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Movement; Polysomnography; Pramipexole; Pregabalin; Restless Legs Syndrome; Sleep; Sleep Wake Disorders; Young Adult

In dialysis patients, painful peripheral neuropathy (PPN) is associated with sleep disturbance and mood disorders. Our goal was to compare the effects of gabapentin and pregabalin on improving sleep quality and depression among hemodialysis patients with PPN.. Fifty hemodialysis patients with PPN were randomized into 2 groups, to receive gabapentin and pregabalin, respectively. After 6 weeks of treatment, patients underwent a 2-week washout period, followed by crossover and another 6 weeks of treatment. All patients underwent electromyography (EMG) at the outset and completed the modified Short Form of McGill Pain Questionnaire (SF-MPQ), the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality (PSQI) assessment at baseline and at the end of the study. Forty out of 50 patients completed the 14-week study period.. Thirty-one out of 40 patients (77.5 %) had EMG-proven PPN. Both gabapentin and pregabalin significantly improved SF-MPQ, BDI and PSQI scores at the end of the study compared with pretreatment scores (p < 0.001). There was no significant difference between the two drugs in any studied parameter.. Our results showed for the first time a good and similar efficacy of both drugs on pain intensity, quality of sleep and depression in hemodialysis patients with PPN.

Topics: Amines; Anti-Anxiety Agents; Calcium Channel Blockers; Cross-Over Studies; Cyclohexanecarboxylic Acids; Depression; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Gabapentin; gamma-Aminobutyric Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peripheral Nervous System Diseases; Pregabalin; Prospective Studies; Quality of Life; Renal Dialysis; Sleep; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome

Chronic pain related to postoperative abdominal adhesions is a common problem with no standard analgesic regimen currently established. In a double-blind, placebo-controlled trial, we examined the effects of pregabalin on pain modulation in patients with prior abdominal surgery and documented adhesion. The primary outcome measure was pain relief documented by a 2-point change on the Likert pain scale with a secondary pain measure of sleep interruption. A total of 18 women were randomized to receive either the drug (n = 11) or placebo (n = 7). Thirteen patients (eight pregabalin, five placebo) completed the blinded phase and 10 patients (seven pregabalin, three placebo) completed the open-label phase. Statistical analysis was performed in two settings: 1) Week 0 (as the baseline) through the end of Week 7 of the blinded fixed-dose phase; and 2) Week 7 (as the baseline) along With weeks 8 through 11 of the open-label phase. The pain score result from the blinded phase setting indicated that the amount of decrease was significantly greater in the drug group (P = 0.024), whereas the pain score result from the open-label setting indicated that the amount of decrease was significantly greater in the placebo group (P = 0.043). Only the sleep score result in the open-label setting was significantly greater in the placebo group (P = 0.024). We conclude that pregabalin significantly reduced patient-documented pain scores compared with placebo in our small cohort of patients with abdominal adhesion pain.

Topics: Abdomen; Abdominal Pain; Adult; Analgesics; Chronic Pain; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Middle Aged; Pain Measurement; Postoperative Complications; Pregabalin; Sleep Wake Disorders; Tissue Adhesions; Treatment Outcome

To assess the effect of pregabalin on polysomnographic (PSG) measures of sleep and patient-rated sleep, tiredness, and pain in fibromyalgia patients.. We performed a randomized, double-blind, placebo-controlled, 2-period crossover PSG study. Patients ages ≥18 years with fibromyalgia satisfied subjective and objective sleep disturbance criteria prior to randomization. Eligible patients were randomized (1:1) to pregabalin (300-450 mg/day) or placebo for crossover period 1, and vice versa for period 2. Each crossover period comprised a dose-adjustment and dose-maintenance phase, with a 2-week taper/washout between periods. In-laboratory PSGs were recorded during 2 consecutive nights at screening and at the end of each crossover period. The primary end point was the difference in sleep maintenance defined by PSG-recorded wake after sleep onset (WASO; minutes) between 4 weeks of treatment with pregabalin and with placebo. Other PSG measures; patient-rated sleep, tiredness, and pain; and tolerability were assessed.. Of 119 patients randomized (103 women [86.6%], mean age 48.4 years), 102 (85.7%) completed both periods. Patients treated with pregabalin showed a reduction in PSG-determined WASO versus treatment with placebo (week 4 difference: -19.2 minutes [95% confidence interval (95% CI) -26.7, -11.6]; P < 0.0001). Pain score improved (decreased) with pregabalin versus placebo treatment at all 4 weeks (week 4 difference: -0.52 [95% CI -0.90, -0.14]; P = 0.0084). Modest (ρ = <0.3) but significant correlations were found between PSG sleep assessments and ratings of pain and sleep quality. Frequently reported all-causality adverse events (pregabalin versus placebo) were: dizziness (30.4% versus 9.9%), somnolence (20.5% versus 4.5%), and headache (8.9% versus 8.1%).. Patients with fibromyalgia treated with pregabalin had statistically significant and meaningful improvements in sleep, as assessed by PSG. Patients with fibromyalgia also reported decreased daily pain. Pregabalin was well tolerated.

Topics: Adult; Aged; Analgesics; Comorbidity; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Fatigue; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Polysomnography; Pregabalin; Self Report; Sleep Wake Disorders; Treatment Outcome

To determine the incidence and duration of response of clinically meaningful improvements with pregabalin across several key symptoms of fibromyalgia (FM).. This was a post hoc analysis of data from a multicenter, double-blind, placebo-controlled, randomized, withdrawal study, originally designed to evaluate the efficacy of pregabalin monotherapy for durability of effect on FM pain based on pain and Patient Global Impression of Change (PGIC) criteria. Responder criteria for Fibromyalgia Impact Questionnaire total score (≥16-point change), Medical Outcomes Study Sleep Scale Sleep Disturbance subscale (≥15.8-point change), and the 36-item Short-Form Health Survey Vitality scale (≥10-point change) were used to evaluate the incidence and duration of improvements in function, sleep, and fatigue for pregabalin versus placebo among pain and PGIC responders. A composite responder index consisting of pain, PGIC, function, and sleep endpoints was used to explore multidimensional response.. Approximately 80% of patients meeting pain and PGIC improvement criteria at randomization had clinically meaningful improvement in fatigue, sleep, or function. Higher proportions of patients in the pregabalin group maintained a clinically meaningful response, and pregabalin-treated patients had a significantly longer time to loss of therapeutic response compared with the placebo group. Composite responder Kaplan-Meier analysis, performed with patients demonstrating clinically meaningful improvements in pain, PGIC, function, and sleep at randomization showed a significantly longer median time to loss of therapeutic response for pregabalin-treated patients.. The results from this post hoc analysis indicate that pregabalin provides long-term effects across multiple domains of FM (ClinicalTrials.gov registry ID: NCT00151489).

Topics: Analgesics; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Fibromyalgia; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Pain Measurement; Pregabalin; Sleep Wake Disorders; Time Factors; Treatment Outcome

Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Prior trials have demonstrated the efficacy of pregabalin for the relief of fibromyalgia symptoms, and it is approved for the treatment of fibromyalgia in the United States. However, prior to this study, there has not been a large-scale efficacy trial in patients with fibromyalgia in Japan.. This randomized, double-blind, multicenter, placebo-controlled trial was conducted at 44 centers in Japan to assess the efficacy and safety of pregabalin for the symptomatic relief of pain in fibromyalgia patients. Patients aged ≥18 years who had met the criteria for fibromyalgia were randomized to receive either pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day, or placebo, for 15 weeks. The primary efficacy endpoint was mean pain score at final assessment. Secondary endpoints included Patient Global Impression of Change (PGIC) together with measures of sleep, physical functioning and quality of life.. A total of 498 patients (89% female) were randomized to receive either pregabalin (n = 250) or placebo (n = 248). Pregabalin significantly reduced mean pain score at final assessment (difference in mean change from baseline, compared with placebo -0.44; P = 0.0046) and at every week during the study (P <0.025). Key secondary endpoints were also significantly improved with pregabalin treatment compared with placebo, including PGIC (percentage reporting symptoms "very much improved" or "much improved", 38.6% vs 26.7% with placebo; P = 0.0078); pain visual analog scale (difference in mean change from baseline, compared with placebo -6.19; P = 0.0013); Fibromyalgia Impact Questionnaire total score (-3.33; P = 0.0144); and quality of sleep score (-0.73; P <0.0001). Treatment was generally well tolerated, with somnolence and dizziness the most frequently reported adverse events.. This trial demonstrated that pregabalin, at doses of up to 450 mg/day, was effective for the symptomatic relief of pain in Japanese patients with fibromyalgia. Pregabalin also improved measures of sleep and functioning and was well tolerated. These data indicate that pregabalin is an effective treatment option for the relief of pain and sleep problems in Japanese patients with fibromyalgia.. ClinicalTrials.gov: NCT00830167.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Incidence; Japan; Male; Middle Aged; Pain Measurement; Pregabalin; Quality of Life; Sleep Wake Disorders; Treatment Outcome

The objective of this study is to use the pain numeric rating scale (NRS) to evaluate associations between change in pain severity and changes in sleep, function, and mood assessed via patient-reported outcomes (PROs) in patients with posttraumatic pain.. This is a secondary analysis of a clinical trial evaluating pregabalin in patients with posttraumatic peripheral neuropathic pain (N = 254). Regression models were used to determine associations between changes in pain (0-10 NRS) as the predictor and scores on the following PRO measures as the outcome: Pain Interference Index; Hospital Anxiety and Depression Scale anxiety and depression subscales; Medical Outcomes Study-Sleep Scale 9-item Sleep Problems Index and Sleep Disturbance subscale; and Daily Sleep Interference Scale (0-10 NRS).. Change in pain severity showed clear, direct relationships with changes in function, anxiety, depression, and sleep PROs, all of which were statistically significant (P <.001). Results from subgroup analyses (≥30% or ≥50% pain responders, pregabalin or placebo treatment, age ≤ 51 years or > 51 years) tended to be consistent with results from the overall sample.. Overall, a direct relationship exists between pain and various aspects of patient's well-being and functioning, which can provide a quantitative assessment of how improvements in pain may be expected to relate to other patient outcomes. (http://ClinicalTrials.gov Identifier number NCT00292188; EudraCT #2005-003048-78).

Topics: Analgesics; Anxiety; Depression; gamma-Aminobutyric Acid; Humans; Neuralgia; Pain Measurement; Pregabalin; Quality of Life; Self Report; Severity of Illness Index; Sickness Impact Profile; Sleep Wake Disorders; Wounds and Injuries

To evaluate the effectiveness of pregabalin as a tapering therapy on the subjective sleep quality of patients who underwent a benzodiazepine withdrawal program in routine medical practice.. Secondary analysis of a 12-week prospective, open noncontrolled study carried out in patients who met DSM-IV-TR criteria for benzodiazepine dependence. Sleep was evaluated with the Medical Outcomes Study Sleep Scale (MOS Sleep Scale).. 282 patients were included in the analysis. Mean (±SD) pregabalin dose was 315 ± 166 mg/day at the end of the trial. We observed a significant and clinically relevant improvement in sleep outcomes at the endpoint, with a total score reduction from 55.8 ± 18.9 to 25.1 ± 18.0 at week 12 (i.e. a 55% reduction). Similar findings were apparent using the six dimensions of the MOS Sleep Scale. Moderate correlations were observed between the MOS Sleep summary index and sleep domains, and there were improvements in anxiety symptoms and disease severity.. These findings suggest that pregabalin may improve subjective sleep quality in patients who underwent a benzodiazepine withdrawal program. This effect appears to be partly independent of improvements in symptoms of anxiety or withdrawal. However, controlled studies are needed to establish the magnitude of the effect of pregabalin.

Topics: Adult; Anti-Anxiety Agents; Anxiety; Benzodiazepines; Female; gamma-Aminobutyric Acid; Humans; Male; Pregabalin; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep; Sleep Wake Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders

To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States.. This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function.. Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events.. Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Double-Blind Method; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Placebos; Pregabalin; Sleep; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome; Young Adult

The objective of this study was to evaluate the effect of patients' characteristics at baseline on the magnitude of pain response to pregabalin in patients with fibromyalgia.. Data from four randomized, multicenter, placebo-controlled clinical studies of pregabalin in patients with fibromyalgia were used for the analysis. Approved doses (300 and 450 mg/day) were pooled to enhance the sensitivity of the interaction tests. A centered covariate interaction model was used to assess the treatment effects; a noncentered model was used for estimated mean pain changes and least square means across different levels of baseline covariates. The interaction was considered significant if p < 0.10.. In total, 2061 patients (median age, 49 years; median pain score, 7.0; median duration of fibromyalgia, 83 months) were included in this analysis. No significant interaction was observed between treatment and anxiety, depression, or duration of fibromyalgia. Significant treatment by baseline mean pain (p = 0.037), treatment by baseline sleep score (p = 0.071), and treatment by age (p = 0.051) interactions were observed.. The magnitude of response to pregabalin in terms of changes in pain may depend on age, pain, and sleep levels at baseline in patients with fibromyalgia.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Analgesics; Anxiety; Depression; Dose-Response Relationship, Drug; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Sleep Wake Disorders; Treatment Outcome

To evaluate the effects of pregabalin (PGB) adjunctive therapy on sleepwake cycle and daytime somnolence in adult patients affected by partial epilepsy.. Twelve patients affected by partial epilepsy underwent a 24-h ambulatory polysomnography and a subjective evaluation of daytime somnolence by means of the Epworth Sleepiness Scale (ESS), before and after 3 months treatment with PGB.. Pregabalin therapy reduced seizures by >50% in 8 out of 12 patients. It induced a significant increase of REM sleep and a decrease of stage 2 NREM sleep (S2). A significant increase of the ESS score was observed without reaching the pathological cut-off value (mean ESS score <10). No statistical correlation between REM sleep and seizure frequency was observed.. Pregabalin seems to be effective and safe in partial epilepsy. The increase of REM sleep may be indicative of an improvement of nocturnal sleep quality considering the involvement of REM sleep in learning and memory processes. REM sleep enhancement may be the result of both a direct effect of PGB on sleep generators and an indirect effect due to its clinical efficacy. The increase of ESS score within normal range suggests that daytime somnolence is a minor adverse effect of PGB.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Polysomnography; Pregabalin; Prospective Studies; Single-Blind Method; Sleep Wake Disorders; Sleep, REM; Young Adult

This trial evaluated the efficacy and safety of pregabalin dosed twice daily (BID) for relief of neuro-pathic pain associated with postherpetic neuralgia (PHN).. The 13-week, double-blind, placebo-controlled study randomized 370 patients with PHN to pregabalin (150, 300, or 600 mg/day BID) or placebo.. Primary efficacy measure was endpoint mean pain score from daily pain diaries. Secondary efficacy measures included endpoint mean sleep-interference score from daily sleep diaries and Patient Global Impression of Change (PGIC). Safety evaluations included adverse events (AEs), physical and neurologic examinations, 12-lead ECG, vital signs, and laboratory testing.. Pregabalin provided significant, dose-proportional pain relief at endpoint: difference from placebo in mean pain score, 150 mg/day, -0.88, p = 0.0077; 300 mg/day, -1.07, p = 0.0016; 600 mg/day, -1.79, p = 0.0003. Weekly mean pain scores significantly improved as early as week 1. Sleep interference in all pregabalin groups was also significantly improved at endpoint, compared with placebo (p < 0.001), beginning at week 1 (p < 0.01). At study termination, patients in the 150 (p = 0.02) and 600 mg/day (p = 0.003) groups were more likely to report global improvement than were those in the placebo group. Most AEs were mild or moderate. Among pregabalin-treated patients, 13.5% withdrew due to AEs, most commonly for dizziness (16 patients, 5.8%), somnolence (8, 2.9%), or ataxia (7, 2.5%).. Pregabalin, dosed BID, reduced neuropathic pain associated with PHN and was well tolerated. It also reduced the extent to which pain interfered with sleep. Pregabalin's effects were seen as early as week 1 and were sustained throughout the 13-week study.

Topics: Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Placebos; Pregabalin; Sleep Wake Disorders; Treatment Outcome

Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel alpha(2)-delta ligand, for treatment of symptoms associated with FMS.. This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group.. Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (-0.93 on a 0-10 scale) (P /=50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups.. Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Placebos; Pregabalin; Quality of Life; Sleep Wake Disorders; Treatment Outcome

This study was designed to assess the efficacy and safety of pregabalin-a novel alpha(2)-delta ligand with analgesic, anxiolytic, and anticonvulsant activity-for treating neuropathic pain in patients with post-herpetic neuralgia (PHN). Two hundred and thirty-eight patients were randomised into this multicentre, doubleblind, placebo-controlled trial to receive 150 (n=81), 300 mg/day (n=76) pregabalin, or placebo (n=81) for 8 weeks. Among the exclusion criteria was failure to respond to previous treatment for PHN with gabapentin at doses > or =1200 mg/day. Endpoint mean pain scores were significantly reduced in patients receiving 150 or 300 mg/day pregabalin compared with placebo. Efficacy was observed as early as week 1 and was maintained throughout the study. Significantly more patients in both pregabalin groups (150 mg, 26%; 300 mg, 28%) were responders (> or =50% decrease in mean pain score from baseline to endpoint) than in the placebo group (10%). Additionally, by week 1 and for the study's duration, 150 and 300 mg/day pregabalin significantly reduced weekly mean sleep interference scores. More pregabalin-treated patients than placebo-treated patients reported that they were 'much improved' or 'very much improved'. Health-related quality-of-life (HRQoL) measurements using the SF-36 Health Survey demonstrated improvement in the mental health domain for both pregabalin dosages, and bodily pain and vitality domains were improved in the 300 mg/day group. The most frequent adverse events were dizziness, somnolence, peripheral oedema, headache, and dry mouth. Pregabalin efficaciously treated the neuropathic pain of PHN. Additionally, pregabalin was associated with decreased sleep interference and significant improvements in HRQoL measures.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Female; gamma-Aminobutyric Acid; Herpes Zoster; Humans; Male; Middle Aged; Mood Disorders; Neuralgia; Pain Measurement; Placebos; Pregabalin; Quality of Life; Sleep Wake Disorders; Treatment Outcome

Despite the importance of sleep and the evidence on its relationship with various chronic diseases, quality of sleep is not considered in patients with lumbar spinal stenosis (LSS). This prospective comparative study aimed to investigate the changes in sleep disturbance after treatment in patients with LSS. Patients with LSS and sleep disturbance (n = 201; 147 conservatively treated and 54 patients with surgical treatment) were included. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality. Propensity score matching was used to attenuate the potential bias. Clinical outcome of surgery, as determined by the Oswestry disability index, and the PSQI was compared between the two groups at 6 weeks, 3 months, and 6 months after enrollment. Multivariate logistic analysis was performed to adjust for possible confounders within the matched cohorts. Among the 201 patients, 96 (47.7%) patients were finally matched (48 patients in each group). Sleep quality was initially improved after treatment, regardless of the treatment method. Sleep quality in the surgical group was improved by 6 weeks after surgery and consistently improved during the 6-month follow-up period, despite less use of pain killer. Conversely, the improvement in sleep quality at 6-weeks following conservative treatment was not maintained during the follow-up, although the treatment outcome for LSS measured by ODI was continuously improved. After multivariate logistic regression analysis within propensity score matched cohorts, surgical treatment had a significantly greater chance to improve sleep quality compared to conservative treatment. The failure of sleep improvement in conservative group was significantly associated with depression presented by worse score in Hamilton depression rating scale, and more severe degree of foraminal-type stenosis, which should be carefully considered for conservative treatment of LSS patients with sleep disturbance.

Topics: Aged; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Conservative Treatment; Decompression, Surgical; Depression; Female; Gabapentin; Humans; Lumbar Vertebrae; Male; Pregabalin; Propensity Score; Prospective Studies; Sleep; Sleep Aids, Pharmaceutical; Sleep Wake Disorders; Spinal Stenosis; Surveys and Questionnaires; Treatment Outcome

Cross-sectional study.. Sleep disturbances are frequently reported by individuals with spinal cord injury (SCI) and are associated both with poor quality of life and reduced ability to participate in rehabilitation and daily life activities.. This study investigated sleep quality based on self-reports and actigraphy in individuals with SCI as compared to able-bodied. We also explored the relationship between sleep quality, physical activity, and neuropathic pain.. Institute Guttmann, Neurorehabilitation Hospital, Badalona, Barcelona, Spain.. Fourteen SCI patients (12 males, 43.10 ± 10.59 y.o.) and 10 healthy individuals (7 males, mean age 46.21 ± 12.58 y.o.) were enrolled in the study. Participants wore wrist actigraphs for 7 consecutive days to characterize their sleep-wake cycle, rest-activity circadian rhythm and physical activity. Sleep quality, chronotype, daytime sleepiness, neuropathic pain severity and interference were assessed based on questionnaires.. SCI individuals reported poorer sleep quality compared to healthy individuals. Actigraphy-based sleep measurements revealed that patients woke up later, spent more time in bed and slept longer compared to the healthy controls but did not differ significantly in the estimated sleep efficacy and number of awakenings from the able-bodied controls. In individuals with SCI greater physical activity predicted higher sleep efficacy and less awakening episodes as well as shorter sleep latency and lower sleep disturbance.. The actigraphy-based sleep estimates indicate that patients with SCI spent more time in bed and slept longer but their sleep efficacy was similar to able-bodied controls. Maintaining regular physical activity could improve pain control and sleep quality.

Topics: Actigraphy; Adult; Analgesics; Benzodiazepines; Case-Control Studies; Exercise; Female; Gabapentin; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Paraplegia; Pregabalin; Sleep; Sleep Latency; Sleep Wake Disorders; Sleepiness; Spinal Cord Injuries

This post hoc analysis used 11 predictive models of data from a large observational study in Germany to evaluate potential predictors of achieving at least 50% pain reduction by week 6 after treatment initiation (50% pain response) with pregabalin (150-600 mg/d) in patients with neuropathic pain (NeP).. The potential predictors evaluated included baseline demographic and clinical characteristics, such as patient-reported pain severity (0 [no pain] to 10 [worst possible pain]) and pain-related sleep disturbance scores (0 [sleep not impaired] to 10 [severely impaired sleep]) that were collected during clinic visits (baseline and weeks 1, 3, and 6). Baseline characteristics were also evaluated combined with pain change at week 1 or weeks 1 and 3 as potential predictors of end-of-treatment 50% pain response. The 11 predictive models were linear, nonlinear, and tree based, and all predictors in the training dataset were ranked according to their variable importance and normalized to 100%.. The training dataset comprised 9187 patients, and the testing dataset had 6114 patients. To adjust for the high imbalance in the responder distribution (75% of patients were 50% responders), which can skew the parameter tuning process, the training set was balanced into sets of 1000 responders and 1000 nonresponders. The predictive modeling approaches that were used produced consistent results. Baseline characteristics alone had fair predictive value (accuracy range, 0.61-0.72; κ range, 0.17-0.30). Baseline predictors combined with pain change at week 1 had moderate predictive value (accuracy, 0.73-0.81; κ range, 0.37-0.49). Baseline predictors with pain change at weeks 1 and 3 had substantial predictive value (accuracy, 0.83-0.89; κ range, 0.54-0.71). When variable importance across the models was estimated, the best predictor of 50% responder status was pain change at week 3 (average importance 100.0%), followed by pain change at week 1 (48.1%), baseline pain score (14.1%), baseline depression (13.9%), and using pregabalin as a monotherapy (11.7%).. The finding that pain changes by week 1 or weeks 1 and 3 are the best predictors of pregabalin response at 6 weeks suggests that adhering to a pregabalin medication regimen is important for an optimal end-of-treatment outcome. Regarding baseline predictors alone, considerable published evidence supports the importance of high baseline pain score and presence of depression as factors that can affect treatment response. Future research would be required to elucidate why using pregabalin as a monotherapy also had more than a 10% variable importance as a potential predictor.

Topics: Adult; Analgesics; Depression; Female; Germany; Humans; Male; Neuralgia; Pain Management; Pain Measurement; Pregabalin; Prospective Studies; Sleep Wake Disorders; Treatment Outcome

To evaluate the antinociceptive and hypnotic effects of pregabalin, we established a neuropathic pain-like model in mice using partial sciatic nerve ligation (PSNL), and examined thermal hyperalgesia, mechanical allodynia, electroencephalogram, rota-rod testing, and c-Fos expression in the anterior cingulate cortex. Gabapentin was used as a reference drug in the study. Pregabalin administered i.g. at 12.5 and 25mg/kg prolonged the duration of thermal latencies by 1.4- and 1.6-fold and increased the mechanical threshold by 2.2- and 3.1-fold 3h after administration, respectively, but did not affect motor coordination in PSNL mice, compared with vehicle control. Pregabalin (12.5 and 25mg/kg) given at 6:30 increased the amount of non-rapid eye movement sleep in a 4-h period by 1.3- and 1.4-fold, respectively, in PSNL mice. However, pregabalin (25mg/kg) given at 20:30 did not alter the sleep pattern in normal mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of anterior cingulate cortex by 2.1-fold, which could be reversed by pregabalin. These results indicate that pregabalin is an effective treatment for both neuropathic pain and sleep disturbance in PSNL mice.

Topics: Amines; Analgesics; Animals; Cerebral Cortex; Cyclohexanecarboxylic Acids; Electroencephalography; Gabapentin; gamma-Aminobutyric Acid; Genes, fos; Hot Temperature; Hyperalgesia; Hypnotics and Sedatives; Male; Mice; Mice, Inbred C57BL; Neuralgia; Pain Measurement; Physical Stimulation; Postural Balance; Pregabalin; Sciatic Neuropathy; Sleep Wake Disorders; Sleep, REM

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

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Female; Humans; Longitudinal Studies; Male; Middle Aged; Models, Statistical; Outpatients; Pregabalin; Prospective Studies; Psychiatric Status Rating Scales; Sleep Wake Disorders; Treatment Outcome

To evaluate the predictive value of disturbed sleep on the ability of pregabalin to reduce pain associated with diabetic peripheral neuropathy (DPN) and post-herpetic neuralgia (PHN).. A post-hoc analysis of data pooled from 16 placebo-controlled trials of pregabalin in patients with DPN or PHN.. Pain relief at endpoint was compared in patients with mild, moderate, or severe levels of baseline sleep disturbance. Sleep disturbance was based on a scale from 0-10 and scores <4, 4 to 7, and ≥7 were classified as mild, moderate, and severe, respectively.. Pregabalin significantly reduced mean pain scores in the DPN (N = 3,056) and PHN (N = 1,471) cohorts (mean placebo-adjusted reductions were -0.73 and -1.08 for patients with DPN/PHN, respectively; both P < 0.05). The greatest extent of pain relief occurred in patients with severe sleep interference scores at baseline. Data analyses using the pooled DPN/PHN population identified a subset of patients (N = 707) exhibiting marked levels of pain relief at endpoint (mean placebo-adjusted reduction of -2.88), all of whom had severe sleep interference scores at baseline. Baseline sleep interference scores were a moderately good predictor of global patient improvement in response to pregabalin treatment in both patient cohorts. Finally, path analysis showed a high degree of association between improvements in sleep and pain relief in patients with DPN/PHN.. Overall, these data suggest that the presence of comorbid sleep disturbance in patients with DPN/PHN might, in part, predict substantial pain relief in response to pregabalin treatment.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Diabetic Neuropathies; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Pregabalin; Severity of Illness Index; Sleep Wake Disorders; Treatment Outcome; Young Adult

Numerous controlled clinical trials have demonstrated the safety and efficacy of pregabalin in the treatment of neuropathic pain. The objectives of the present study were to assess the impact of pregabalin under real-world conditions on pain, pain-related sleep interference and general well-being, and to assess the tolerability and safety of pregabalin in patients diagnosed with neuropathic pain of central or peripheral origin.. This was a non-interventional, multicentre study in which pregabalin was administered for 8 weeks, at the therapeutic dosages of 150-600 mg/day, to patients with a diagnosis of neuropathic pain. Pain intensity and pain-related sleep interference were measured using 11-point numerical rating scales, while well-being was assessed by documenting how often emotions associated with anxiety or depression were felt over the past week. Patient and Clinician Global Impression of Change (PGIC and CGIC) were assessed at the final visit.. In the 668 patients included in the full analysis set, there were significant (p < 0.0001) reductions in mean pain and pain-related sleep interference scores of 4.16 and 4.02, respectively. Indicators of general well-being showed improvement from baseline to final visit. The majority of patients were rated as 'much improved' (43.7% and 36.7%) or 'very much improved' (24.0% and 26.2%) on CGIC and PGIC scores, respectively. Discontinuation because of lack of efficacy occurred in 0.7% of 691 patients in the safety analysis set while discontinuation because of adverse events occurred in 5.1% of this population; 76.4% continued treatment after the study ended.. Significant reductions in pain and pain-related sleep interference, combined with reductions in feelings of anxiety and depression, suggest that pregabalin under real-world conditions improves the overall health and well-being of patients with neuropathic pain.

Topics: Aged; Analgesics; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Peripheral Nervous System Diseases; Pregabalin; Product Surveillance, Postmarketing; Sleep Wake Disorders; Surveys and Questionnaires

To evaluate the effect of pregabalin on different patient-reported outcomes in subjects with neuropathic pain treated under usual medical practice conditions in primary care settings.. Secondary analysis of a 12-week, multicenter, naturalistic, and prospective study on 18 years of age or older patients of both genders with chronic pain (of at least 6 months) due to diabetic neuropathy, post-herpetic, or trigeminal neuralgia refractory to the previous analgesic treatment (at least one drug).. Assessed at baseline and end of the study visits by the following questionnaires: Short Form McGill Pain Questionnaire, Sheehan Disability Inventory, Medical Outcomes Study Sleep Scale, Hospital Anxiety and Depression Scale, and EQ-5D.. The analysis included 1,354 patients not previously exposed to pregabalin; 598 patients (44%) received monotherapy with pregabalin as a substitute of the previous treatment, in 589 patients (44%) pregabalin was added to the existing therapy, and the treatment schedule of the other 167 patients (12%) did not include pregabalin. After 12 weeks of treatment, significant improvements in all effectiveness assessments were observed in all of the three groups, these being significantly greater in the groups receiving pregabalin, with large effect sizes in most health outcome measures.. Under usual medical practice conditions, patients with chronic pain of peripheral neuropathic origin receiving pregabalin both in monotherapy and as add-on therapy showed substantial improvements in severity of pain and in the spectrum of associated symptoms, such as sleep disturbances, mood disorders, disability, and health-related quality of life. Further clinical trials are needed to confirm these findings.

Topics: Adult; Aged; Analgesics; Female; gamma-Aminobutyric Acid; Health Status; Humans; Middle Aged; Multicenter Studies as Topic; Neuralgia; Pain Measurement; Pregabalin; Primary Health Care; Prospective Studies; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome

Efficacy and tolerability of a new antiepileptic drug pregabalin (lyrica) as an add-on drug in patients with focal refractory epilepsy was analyzed. The most commonly used dosage was 450 mg/d. For the 6-month treatment of 19 patients, aged 18-30 years, a positive effect of the combined therapy was observed in 68,4%, the remission was achieved in 31,6% and the significant improvement in 36,8%. Drug was discontinued due to the lack of efficacy and intolerance in 31,6%. Drowsiness was the most frequent adverse event and hemorrhagic vasculitis was registered in one patient. Two cases of effective use of the drug during pregnancy with the birth of healthy children are reported. A case of the high efficacy of pregabalin in migraine-epilepsy is described. High efficacy and good tolerability as well as favorable pharmacokinetic characteristics and distinct anxyolytic effect give indications for use of pregabalin in clinical practice.

Topics: Adolescent; Adult; Anticonvulsants; Combined Modality Therapy; Epilepsies, Partial; Female; gamma-Aminobutyric Acid; Humans; IgA Vasculitis; Male; Migraine Disorders; Pregabalin; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Remission Induction; Sleep Wake Disorders; Treatment Outcome; Young Adult

Topics: Amyloid; Analgesics; Anticonvulsants; Antiparkinson Agents; Diabetes Mellitus, Type 2; Diphtheria-Tetanus-Pertussis Vaccine; Drug Approval; Drug Combinations; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Exenatide; gamma-Aminobutyric Acid; Heart Failure; Humans; Hydralazine; Hypoglycemic Agents; Indenes; Indoles; Islet Amyloid Polypeptide; Isosorbide Dinitrate; Patient Education as Topic; Patient Selection; Peptides; Pregabalin; Sleep Wake Disorders; United States; United States Food and Drug Administration; Venoms