Pregabalin In Fibromyalgia Research Articles

Combination analgesic development for enhanced clinical efficacy (the CADENCE trial): a double-blind, controlled trial of an alpha-lipoic acid-pregabalin combination for fibromyalgia pain.

Drug therapy for fibromyalgia is limited by incomplete efficacy and dose-limiting adverse effects (AEs). Combining agents with complementary analgesic mechanisms-and differing AE profiles-could provide added benefits. We assessed an alpha-lipoic acid (ALA)-pregabalin combination with a randomized, double-blind, 3-period crossover design. Participants received maximally tolerated doses of ALA, pregabalin, and ALA-pregabalin combination for 6 weeks. The primary outcome was daily pain (0-10); secondary outcomes included Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. The primary outcome of daily pain (0-10) during ALA (4.9), pregabalin (4.6), and combination (4.5) was not significantly different (P = 0.54). There were no significant differences between combination and each monotherapy for any secondary outcomes, although combination and pregabalin were both superior to ALA for measures of mood and sleep. Alpha-lipoic acid and pregabalin maximal tolerated doses were similar during combination and monotherapy, and AEs were not frequent with combination therapy. These results do not support any additive benefit of combining ALA with pregabalin for fibromyalgia. The observation of similarly reached maximal tolerated drug doses of these 2 agents (which have differing side-effect profiles) during combination and monotherapy-without increased side effects-provides support for future development of potentially more beneficial combinations with complementary mechanisms and nonoverlapping side effects.

Pregabalin administration in patients with fibromyalgia: a Bayesian network meta-analysis

Several studies investigated the effectiveness and the safety of different doses of pregabalin in fibromyalgia. However, the optimal protocol remains controversial. A Bayesian network meta-analysis comparing 300, 450, and 600 mg/daily of pregabalin for fibromyalgia was conducted. The literature search was conducted in January 2022. All the double-blind randomised clinical trials comparing two or more dose protocols of pregabalin for fibromyalgia were accessed. Studies enrolling less than 50 patients were not eligible, nor were those with a length of follow-up shorter than eight weeks. The outcomes of interests were: Fibromyalgia Impact Questionnaire (FIQ), sleep quality, and adverse events. The network meta-analyses were performed using the routine for Bayesian hierarchical random-effects model analysis, with log odd ratio (LOR) and standardized mean difference (SMD) effect measure. Data from 4693 patients (mean age 48.5 years) were retrieved. 93.1% (4370 of 4693 patients) were women. The median follow-up was 14.8 weeks. Pregabalin 450 mg/daily resulted in greater reduction in Fibromyalgia Impact Questionnaire (SMD − 1.83). Pregabalin 600 demonstrated the greatest sleep quality (SMD 0.15). Pregabalin 300 mg/daily evidenced the lowest rate of adverse events (LOR 0.12). The dose of pregabalin must be customised according to patients’ characteristics and main symptoms.

Can the long term using of pregabalin in fibromyalgia affect the choroid and retinal nerve fiber layer?

In this study, the effects of long-term pregabalin use on the choroid and retinal nerve fiber layer were investigated in the fibromyalgia disease. The patient group consisted of 41 fibromyalgia patients using pregabalin. The control group consisted of 41 newly diagnosed fibromyalgia patients who had not received any treatment yet. Choroidal and retinal nerve fiber layer thickness measurements were performed with Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA, USA) 30 minutes after pupil dilation with 1% tropicamide. There was no difference in subfoveal choroidal thickness, nasal choroidal thickness and temporal choroidal thickness between the patient and control groups (p > 0.05). Increasing the duration of drug use within the patient group was found to thin the retinal nerve fiber layer (p < 0.05). We found that pregabalin had no effect on the choroid, while it had a thinning effect for retinal nerve fiber layer. It is recommended not to be preferred pregabalin in fibromyalgia patients with retinal nerve fiber layer damage such as diabetic retinopathy and glaucoma. Patients treated with pregabalin should have regular control in the ophthalmology clinic.

WITHDRAWN: Anticonvulsants for fibromyalgia.

Fibromyalgia (FM) is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. People often report high disability levels and poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key symptoms and disability, and improving HRQoL. Anticonvulsants (antiepileptic drugs) are drugs frequently used for the treatment of chronic pain syndromes. To assess the benefits and harms of anticonvulsants for treating FM symptoms. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2013), MEDLINE (1966 to August 2013), PsycINFO (1966 to August 2013), SCOPUS (1980 to August 2013) and the reference lists of reviewed articles for published studies and www.clinicaltrials.gov (to August 2013) for unpublished trials. We selected randomised controlled trials of any formulation of anticonvulsants used for the treatment of people with FM of any age. Two review authors independently extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. We included eight studies: five with pregabalin and one study each with gabapentin, lacosamide and levetiracetam. A total of 2480 people were included into anticonvulsants groups and 1099 people in placebo groups. The median therapy phase of the studies was 13 weeks. The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin, lacosamide and levetiracetam in FM. The amount and quality of evidence was sufficient to draw definite conclusions on the efficacy and safety of pregabalin in FM. Therefore, we focused on our interpretation of the evidence for pregabalin due to our greater certainty about its effects and its greater relevance to clinical practice. All pregabalin studies had a low risk of bias. Reporting a 50% or greater reduction in pain was more frequent with pregabalin use than with a placebo (risk ratio (RR) 1.59; 95% confidence interval (CI) 1.33 to 1.90; number needed to treat for an additional beneficial outcome (NNTB) 12; 95% CI 9 to 21). The number of people who reported being 'much' or 'very much' improved was higher with pregabalin than with placebo (RR 1.38; 95% CI 1.23 to 1.55; NNTB 9; 95% CI 7 to 15). Pregabalin did not substantially reduce fatigue (SMD -0.17; 95% CI -0.25 to -0.09; 2.7% absolute improvement on a 1 to 50 scale) compared with placebo. Pregabalin had a smallbenefit over placebo in reducing sleep problems by 6.2% fewer points on a scale of 0 to 100 (standardised mean difference (SMD) -0.35; 95% CI -0.43 to -0.27). The dropout rate due to adverse events was higher with pregabalin use than with placebo use (RR 1.68; 95% CI 1.36 to 2.07; number needed to treat for an additional harmful outcome (NNTH) 13; 95% CI 9 to 23). There was no significant difference in serious adverse events between pregabalin and placebo use (RR 1.03; 95% CI 0.71 to 1.49). Dizziness was reported as an adverse event more frequently with pregabalin use than with placebo use (RR 3.77; 95% CI 3.06 to 4.63; NNTH 4; 95% CI 3 to 5). The anticonvulsant, pregabalin, demonstrated a small benefit over placebo in reducing pain and sleep problems. Pregabalin use was shown not to substantially reduce fatigue compared with placebo. Study dropout rates due to adverse events were higher with pregabalin use compared with placebo. Dizziness was a particularly frequent adverse event seen with pregabalin use. At the time of writing this review, pregabalin is the only anticonvulsant drug approved for treating FM in the US and in 25 other non-European countries. However, pregabalin has not been approved for treating FM in Europe. The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin, lacosamide and levetiracetam in FM.

Clinical Use of Pregabalin in General Practice in Catalonia, Spain: A Population-Based Cross-Sectional Study.

The aim of this study was to determine the pattern of use of pregabalin and the appropriateness of treatment, so that interventions could be designed to improve various clinical approaches to the use of pregabalin to include unlicensed indications. A descriptive, cross-sectional, multicenter study was performed between April 2014 and January 2015. Fifty-three primary health care centers covering 1,250,000 inhabitants. A total of 10,155 patients with pregabalin prescriptions. Demographic (gender, age) and clinical (licensed indications for pregabalin, treatment duration, dosing schedule, diagnoses, kidney function, previous treatment with pregabalin, and additional drug treatment combined with pregabalin) variables obtained from health records were studied. The indicators were related to the daily dose of pregabalin, diagnoses, and treatment. A total of 64.2% of patients treated with pregabalin were female (mean age = 62.3 years; SD = 15.2 years). Twenty-nine patients were younger than age 18 years. A total of 68.2% of patients were taking pregabalin for an appropriate indication, 45.2% were using pregabalin off-label for bone and joint pain, and 15.1% were using pregabalin for fibromyalgia. A total of 71.9% of patients started treatment with pregabalin without previously using firstline drugs, such as amitriptyline or gabapentin, and 66% of active treatments had been initiated during the year before the study. In 47% of patients with glomerular filtration rates lower than 15 mL/min, the dose exceeded the maximum. Our study reveals that pregabalin is used for unlicensed indications and often when firstline drugs have not been trialed and suggests that better routines in diagnosis and prescription may improve treatment outcomes. Our study also provides novel information about the use of doses of pregabalin that are higher than recommended for patients with renal impairment.

Patterns of health care utilization related to initiation of amitriptyline, duloxetine, gabapentin, or pregabalin in fibromyalgia.

IntroductionSeveral pharmacologic treatments are available for fibromyalgia, but little is known about the comparative effectiveness of these treatments on health care utilization.MethodsUsing US commercial insurance claims data (covering 2007 to 2009), we conducted a cohort study to examine the comparative effectiveness of amitriptyline, duloxetine, gabapentin, and pregabalin on health care utilization in patients with fibromyalgia. We measured patients’ medication adherence using the proportion of days covered (PDC) and estimated multivariable rate ratios (RRs) for outpatient visits, prescriptions, hospitalization, and emergency department (ED) visits in propensity score (PS)–matched cohorts.ResultsCohorts of 8,269 amitriptyline, 9,941 duloxetine, and 18,613 gabapentin initiators were compared with their PS-matched pregabalin initiators. During the baseline 180-day period, patients had, on average, seven to nine physician visits, including six to eight specialist visits, and received eight prescription drugs. The mean PDC up to 180 days varied from 38.6% to 67.7%. The number of outpatient visits, prescriptions, and hospitalizations decreased slightly after initiating one of the study drugs, but the number of ED visits increased after treatment initiation. Compared to pregabalin, duloxetine was associated with decreased outpatient visits (RR, 0.94; 95% confidence interval (CI), 0.88 to 1.00), prescriptions (RR, 0.94; 95% CI, 0.90 to 0.98), hospitalizations (RR, 0.75; 95% CI, 0.68 to 0.83), and ED visits (RR, 0.85; 95% CI, 0.79 to 0.91). Little difference in health care utilization rates was noted among amitriptyline and gabapentin initiators compared to those who were started on pregabalin.ConclusionsFibromyalgia patients had high health care utilization before and after initiation of amitriptyline, duloxetine, gabapentin, or pregabalin. Medication adherence was suboptimal. Overall, fibromyalgia treatment had little impact on reducing health care utilization, but duloxetine initiators had less health care utilization than those started on pregabalin.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0530-8) contains supplementary material, which is available to authorized users.

THU0323 Basal Fmri Differences between Milnacipran Responders and Non-Responder in Fibromyalgia

BackgroundThere were comparison studies of regional cerebral blood flow between the responder group and the poor responder group to gabapentin and pregabalin in fibromyalgia (FM). Other brain imaging studies, such...

Milnacipran combined with pregabalin in fibromyalgia: a randomized, open-label study evaluating the safety and efficacy of adding milnacipran in patients with incomplete response to pregabalin

To evaluate the safety, tolerability, and efficacy of adding milnacipran to pregabalin in patients with fibromyalgia who have experienced an incomplete response to pregabalin. In this randomized, multicenter, open-label study, patients received pregabalin 300 or 450 mg/day during a 4- to 12-week run-in period. Patients with weekly recall visual analog scale (VAS) pain score of at least 40 and up to 90, Patient Global Impression of Severity score of at least 4, and Patient Global Impression of Change (PGIC) score of at least 3 were classified as incomplete responders and randomized to continue pregabalin alone (n = 180) or receive milnacipran 100 mg/day added to pregabalin (n = 184). The primary efficacy parameter was responder status based on PGIC score of up to 2. The secondary efficacy parameter was change from randomization in weekly recall VAS pain score. Safety parameters included adverse events (AEs), vital signs, and clinical laboratory tests. The percentage of PGIC responders was significantly higher with milnacipran added to pregabalin (46.4%) than with pregabalin alone (20.8%; p < 0.001). Mean improvement from randomization in weekly recall VAS pain scores was greater in patients receiving milnacipran added to pregabalin (-20.77) than in patients receiving pregabalin alone (-6.43; p < 0.001). During the run-in period, the most common treatment-emergent AEs with pregabalin were dizziness (22.8%), somnolence (17.3%), and fatigue (9.1%). During the randomized period, the most common treatment-emergent AEs with milnacipran added to pregabalin were nausea (12.5%), fatigue (10.3%), and constipation (9.8%). In this exploratory, open-label study, adding milnacipran to pregabalin improved global status, pain, and other symptoms in patients with fibromyalgia with an incomplete response to pregabalin treatment.

Relationships Among Pain and Depressive and Anxiety Symptoms in Clinical Trials of Pregabalin in Fibromyalgia

Fibromyalgia, as defined by the American College of Rheumatology, is characterized by widespread pain lasting for at least 3 months, with pain in at least 11 out of 18 tender points when palpated with digital pressure. The authors investigated the relationship between changes in pain and symptoms of anxiety and depression, using data from pregabalin clinical trials. Results from three double-blind, placebo-controlled trials of pregabalin monotherapy in fibromyalgia (8-14 weeks) were pooled, and baseline to end-point changes in pain and Hospital Anxiety and Depression Scale (HADS) scores were analyzed. Path-analysis evaluated the association between improvements in anxiety and depression and pain relief. Baseline HADS scores indicated moderate-to-severe anxiety in 38% of patients and moderate-to-severe depressive symptoms in 27%. The improvement in pain was not related to baseline levels of anxiety or depression. The correlation between changes in pain and depressive or anxiety symptoms was low-to-moderate. Path-analysis showed that most of the pain relief observed with pregabalin treatment was a direct analgesic effect and was not explained by improvement in mood. Response to treatment of pain in the pregabalin trials did not depend on baseline levels of anxiety or depressive symptoms, and pregabalin improved pain in fibromyalgia patients with or without depressive or anxiety symptoms. Changes in the level of anxiety or depression had a low-to-moderate impact on pain reduction. Pain reduction with pregabalin treatment appeared to result mostly from a direct treatment effect, rather than an indirect effect mediated through improvement in anxiety or depressive symptoms.

Relationships Among Pain and Depressive and Anxiety Symptoms in Clinical Trials of Pregabalin in Fibromyalgia

Fibromyalgia, as defined by the American College of Rheumatology, is characterized by widespread pain lasting for at least 3 months, with pain in at least 11 out of 18 tender points when palpated with digital pressure.The authors investigated the relationship between changes in pain and symptoms of anxiety and depression, using data from pregabalin clinical trials.Results from three double-blind, placebo-controlled trials of pregabalin monotherapy in fibromyalgia (8-14 weeks) were pooled, and baseline to end-point changes in pain and Hospital Anxiety and Depression Scale (HADS) scores were analyzed. Path-analysis evaluated the association between improvements in anxiety and depression and pain relief.Baseline HADS scores indicated moderate-to-severe anxiety in 38% of patients and moderate-to-severe depressive symptoms in 27%. The improvement in pain was not related to baseline levels of anxiety or depression. The correlation between changes in pain and depressive or anxiety symptoms was low-to-moderate. Path-analysis showed that most of the pain relief observed with pregabalin treatment was a direct analgesic effect and was not explained by improvement in mood.Response to treatment of pain in the pregabalin trials did not depend on baseline levels of anxiety or depressive symptoms, and pregabalin improved pain in fibromyalgia patients with or without depressive or anxiety symptoms. Changes in the level of anxiety or depression had a low-to-moderate impact on pain reduction. Pain reduction with pregabalin treatment appeared to result mostly from a direct treatment effect, rather than an indirect effect mediated through improvement in anxiety or depressive symptoms.

Pregabalin in fibromyalgia - responder analysis from individual patient data

BackgroundPopulation mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores.MethodsWe obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (≥ 0%), minimal improvement (≥ 15%), moderate improvement (≥ 30%), substantial improvement (≥ 50%), and extensive improvement (≥ 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo.ResultsInformation from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs (with 95% confidence intervals) for ≥ 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for ≥ 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response.ConclusionsResponder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects.

Pregabalin in fibromyalgia: meta-analysis of efficacy and safety from company clinical trial reports

Meta-analysis of pregabalin trials in FM using company trial reports, which provide more detailed information about trials than published papers. FM is a common condition with a significant impact on quality of life. Reports of five high-quality randomized trials (3808 patients) of pregabalin in FM were obtained from Pfizer. Four trials (2754 patients) were of classical trial design and one was an enriched enrolment randomized withdrawal design. Outcomes for meta-analysis from the four trials with classical design were pooled in an intention-to-treat analysis. Significant benefit of pregabalin over placebo was seen for a variety of outcomes including mean pain and sleep scores, the proportion of patients achieving at least 50% pain relief and most of the individual domains of short-form 36. Only a minority of patients achieve moderate or substantial pain relief. The proportions of patients with any adverse event, somnolence or dizziness were also significantly greater with pregabalin than with placebo. There was no difference with regard to serious adverse events. A dose-response relationship was apparent for at least 50% pain relief and for adverse event outcomes. Pregabalin is effective in treating FM and is relatively safe. The size of therapeutic effect is similar to that with other recent interventions such as duloxetine and the combination of tramadol and paracetamol. Enriched enrolment randomized withdrawal design gives similar results to classical trial designs in FM.

Pregabalin for fibromyalgia (April 2009)

Pregabalin for fibromyalgia (April 2009)

In reply: Pregabalin for fibromyalgia (April 2009)

In reply: Pregabalin for fibromyalgia (April 2009)