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American Family Physician Feb 2023Fibromyalgia is a chronic, centralized pain syndrome characterized by disordered processing of painful stimuli. Fibromyalgia is diagnosed more frequently in women and...
Fibromyalgia is a chronic, centralized pain syndrome characterized by disordered processing of painful stimuli. Fibromyalgia is diagnosed more frequently in women and occurs globally, affecting 2% of people in the United States. Patients with fibromyalgia have diffuse chronic pain, poor sleep, fatigue, cognitive dysfunction, and mood disturbances. Comorbid conditions, such as functional somatic syndromes, psychiatric diagnoses, and rheumatologic conditions may be present. The Fibromyalgia Rapid Screening Tool is a helpful screening method for patients with diffuse chronic pain. The American College of Rheumatology criteria or the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy diagnostic criteria can diagnose fibromyalgia. Establishing the diagnosis and providing education can reassure patients and decrease unnecessary testing. A multidisciplinary approach that incorporates nonpharmacologic therapies and medications to address problematic symptoms is most effective. Patient education, exercise, and cognitive behavior therapy can improve pain and function. Duloxetine, milnacipran, pregabalin, and amitriptyline are potentially effective medications for fibromyalgia. Nonsteroidal anti-inflammatory drugs and opioids have not demonstrated benefits for fibromyalgia and have significant limitations.
Topics: Humans; Female; Fibromyalgia; Chronic Pain; Pregabalin; Analgesics; Duloxetine Hydrochloride
PubMed: 36791450
DOI: No ID Found -
BMJ Open Jan 2019To assess the benefits and harms of pregabalin in the management of neuropathic pain. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the benefits and harms of pregabalin in the management of neuropathic pain.
DESIGN
Rapid review and meta-analysis of phase III, randomised, placebo-controlled trials.
PARTICIPANTS
Adults aged 18 years and above with neuropathic pain defined according to the International Association for the Study of Pain criteria.
INTERVENTIONS
Pregabalin or placebo.
PRIMARY AND SECONDARY OUTCOME MEASURES
Our primary outcomes were pain (as measured using validated scales) and adverse events. Our secondary outcomes were sleep disturbance, quality of life, Patient Global Impression of Change, Clinician Global Impression scale, anxiety and depression scores, overall discontinuations and discontinuations because of adverse events.
RESULTS
We included 28 trials comprising 6087 participants. The neuropathic pain conditions studied were diabetic peripheral neuropathy, postherpetic neuralgia, herpes zoster, sciatica (radicular pain), poststroke pain and spinal cord injury-related pain. Patients who took pregabalin reported significant reductions in pain (numerical rating scale (NRS)) compared with placebo (standardised mean difference (SMD) -0.49 (95% CI -0.66 to -0.32, p<0.00001), very low quality evidence). Pregabalin significantly reduced sleep interference scores (NRS) compared with placebo (SMD -0.38 (95% CI -0.50 to -0.26, p<0.00001), moderate quality evidence. Pregabalin significantly increased the risk of adverse events compared with placebo (RR 1.33 (95% CI 1.23 to 1.44, p<0.00001, low quality evidence)). The risks of experiencing weight gain, somnolence, dizziness, peripheral oedema, fatigue, visual disturbances, ataxia, non-peripheral oedema, vertigo and euphoria were significantly increased with pregabalin. Pregabalin was significantly more likely than placebo to lead to discontinuation of the drug because of adverse events (RR 1.91 (95% CI 1.54 to 2.37, p<0.00001), low quality evidence).
CONCLUSION
Pregabalin has beneficial effects on some symptoms of neuropathic pain. However, its use significantly increases the risk of a number of adverse events and discontinuation due to adverse events. The quality of the evidence from journal publications is low.
Topics: Adult; Analgesics; Clinical Trials, Phase III as Topic; Double-Blind Method; Humans; Neuralgia; Pregabalin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30670513
DOI: 10.1136/bmjopen-2018-023600 -
Current Medical Research and Opinion Apr 2018Gabapentin (Neurontin ) and pregabalin (Lyrica ) are first- and second-generation α2δ ligands, respectively, and are both approved for use as adjunctive therapy in... (Review)
Review
Gabapentin (Neurontin ) and pregabalin (Lyrica ) are first- and second-generation α2δ ligands, respectively, and are both approved for use as adjunctive therapy in pain control. Although they do not bind to gamma-aminobutyric acid (GABA) receptors they have been successfully used to treat neuropathic pain conditions. Their mechanism of action is not yet fully understood, but research has demonstrated promising results. Despite their similarities, they have been used in combination in both clinical and research situations, and have been noted to have a synergistic effect in pain control without concern for clinically significant pharmacokinetic interactions. This combined approach can be made use of to reduce the dose of an individual agent, its side effects, and to enhance therapeutic response compared to a single agent. Pharmacokinetics, drug interactions, and adverse reaction to combinations have to be taken into consideration before combination therapy with gabapentin and pregabalin is proposed as first-line treatment in refractory pain situations and in patients with low levels of tolerance for an individual agent.
Topics: Analgesics; Drug Therapy, Combination; Gabapentin; Humans; Neuralgia; Pregabalin
PubMed: 29023146
DOI: 10.1080/03007995.2017.1391756 -
Clinical Pharmacology in Drug... Mar 2018
Topics: Anti-Anxiety Agents; Anxiety Disorders; GABA Agents; Gabapentin; Humans; Pregabalin; Treatment Outcome
PubMed: 29579375
DOI: 10.1002/cpdd.446 -
Drugs Jan 2021A 2017 systematic review (SR) identified 59 studies examining gabapentinoid (pregabalin and gabapentin) misuse/abuse. Evidence of gabapentinoid misuse/abuse has since...
BACKGROUND
A 2017 systematic review (SR) identified 59 studies examining gabapentinoid (pregabalin and gabapentin) misuse/abuse. Evidence of gabapentinoid misuse/abuse has since grown substantially.
OBJECTIVE
Update previous SR and describe new insights regarding gabapentinoid abuse.
METHODS
A SR of PubMed was conducted to identify studies published from 7/29/2016-8/31/2020. Four searches were performed using the following terms: "gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid" AND one of the following substance misuse/abuse-related terms: "substance-related disorders [MeSH]", "overdose", "abuse", or "misuse". Clinicaltrials.gov and the Cochrane Library database were searched to identify ongoing studies or similar SRs. Reference lists of included studies were reviewed to identify additional literature. All studies with novel data related to pregabalin and/or gabapentin abuse, misuse, or overdose conducted during the study period were included. Articles not written in English, review articles, and animal studies were excluded.
RESULTS
Fifty-five studies were included (29 [52.7%] from North America, 17 [30.9%] Europe, 6 [10.9%] Asia, and 3 [5.5%] Australia). Forty-six observational studies and 10 case reports/series were included (one manuscript included both). Twenty (36.4%) studied gabapentin only, 18 (32.7%) pregabalin only, and 17 (30.9%) both pregabalin/gabapentin. These studies corroborate findings from the previous SR that gabapentinoids are increasingly abused or misused to self-medicate, that gabapentinoids can produce desirable effects alone but are often used concomitantly with other drugs, and that opioid use disorder is the greatest risk factor for gabapentinoid abuse. While the original SR identified the largest studies having been published in Europe, this review identified several more generalisable US studies that have subsequently been conducted. The most concerning finding was increased evidence of associated patient harm, including increased hospital utilisation and opioid-related overdose mortality risk.
CONCLUSION
Evidence suggests that gabapentinoid misuse/abuse represents a growing trend that is causing significant patient harm. Prescribers should exercise appropriate caution with use in high-risk populations and monitor for signs of misuse or abuse.
Topics: Animals; Drug Overdose; Gabapentin; Humans; Pregabalin
PubMed: 33215352
DOI: 10.1007/s40265-020-01432-7 -
Expert Review of Neurotherapeutics Jun 2023Generalized Anxiety Disorder (GAD) is a common psychiatric condition, characterized by the presence of general apprehensiveness and excessive worry. Current management... (Review)
Review
INTRODUCTION
Generalized Anxiety Disorder (GAD) is a common psychiatric condition, characterized by the presence of general apprehensiveness and excessive worry. Current management consists of a range of pharmacological and psychological treatments. However, many patients do not respond to first-line pharmacological treatments and novel anxiolytic drugs are being developed.
AREAS COVERED
In this review, the authors first discuss the diagnostic criteria and epidemiology of GAD. The effective pharmacological treatments for GAD and their tolerability are addressed. Current consensus guidelines for treatment of GAD are discussed, and maintenance treatment, the management of treatment resistance, and specific management of older adults and children/adolescents are considered. Finally, novel anxiolytics under development are discussed, with a focus on those which have entered clinical trials.
EXPERT OPINION
A range of effective treatments for GAD are available, particularly duloxetine, escitalopram, pregabalin, quetiapine, and venlafaxine. There is a limited evidence base to support the further pharmacological management of patients with GAD who have not responded to initial treatment. Although many novel anxiolytics have progressed to clinical trials, translation from animal models has been mostly unsuccessful. However, the potential of several compounds including certain psychedelics, ketamine, oxytocin, and agents modulating the orexin, endocannabinoid, and immune systems merits further study.
Topics: Humans; Anti-Anxiety Agents; Anxiety Disorders; Duloxetine Hydrochloride; Pregabalin; Treatment Outcome
PubMed: 37183813
DOI: 10.1080/14737175.2023.2211767 -
Current Pain and Headache Reports Aug 2022Painful diabetic neuropathy (PDN) manifests with pain typically in the distal lower extremities and can be challenging to treat. The authors appraised the literature for... (Review)
Review
PURPOSE OF REVIEW
Painful diabetic neuropathy (PDN) manifests with pain typically in the distal lower extremities and can be challenging to treat. The authors appraised the literature for evidence on conservative, pharmacological, and neuromodulation treatment options for PDN.
RECENT FINDINGS
Intensive glycemic control with insulin in patients with type 1 diabetes may be associated with lower odds of distal symmetric polyneuropathy compared to patients who receive conventional insulin therapy. First-line pharmacologic therapy for PDN includes gabapentinoids (pregabalin and gabapentin) and duloxetine. Additional pharmacologic modalities that are approved by the Food and Drug Administration (FDA) but are considered second-line agents include tapentadol and 8% capsaicin patch, although studies have revealed modest treatment effects from these modalities. There is level I evidence on the use of dorsal column spinal cord stimulation (SCS) for treatment of PDN, delivering either a 10-kHz waveform or tonic waveform. In summary, this review provides an overview of treatment options for PDN. Furthermore, it provides updates on the level of evidence for SCS therapy in cases of PDN refractory to conventional medical therapy.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Gabapentin; Humans; Insulins; Pregabalin; Spinal Cord Stimulation
PubMed: 35716275
DOI: 10.1007/s11916-022-01061-7 -
The Cochrane Database of Systematic... Jan 2019This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to nervous tissue). Antiepileptic drugs have long been used in pain management. Pregabalin is an antiepileptic drug used in management of chronic pain conditions.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of pregabalin for chronic neuropathic pain in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from January 2009 to April 2018, online clinical trials registries, and reference lists.
SELECTION CRITERIA
We included randomised, double-blind trials of two weeks' duration or longer, comparing pregabalin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality and biases. Primary outcomes were: at least 30% pain intensity reduction over baseline; much or very much improved on the Patient Global Impression of Change (PGIC) Scale (moderate benefit); at least 50% pain intensity reduction; or very much improved on PGIC (substantial benefit). We calculated risk ratio (RR) and number needed to treat for an additional beneficial (NNTB) or harmful outcome (NNTH). We assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included 45 studies lasting 2 to 16 weeks, with 11,906 participants - 68% from 31 new studies. Oral pregabalin doses of 150 mg, 300 mg, and 600 mg daily were compared with placebo. Postherpetic neuralgia, painful diabetic neuropathy, and mixed neuropathic pain predominated (85% of participants). High risk of bias was due mainly to small study size (nine studies), but many studies had unclear risk of bias, mainly due to incomplete outcome data, size, and allocation concealment.Postherpetic neuralgia: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (50% vs 25%; RR 2.1 (95% confidence interval (CI) 1.6 to 2.6); NNTB 3.9 (3.0 to 5.6); 3 studies, 589 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (32% vs 13%; RR 2.5 (95% CI 1.9 to 3.4); NNTB 5.3 (3.9 to 8.1); 4 studies, 713 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (62% vs 24%; RR 2.5 (95% CI 2.0 to 3.2); NNTB 2.7 (2.2 to 3.7); 3 studies, 537 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (41% vs 15%; RR 2.7 (95% CI 2.0 to 3.5); NNTB 3.9 (3.1 to 5.5); 4 studies, 732 participants, moderate-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 16% versus 5.5%, 600 mg 25% versus 5.8%; dizziness 300 mg 29% versus 8.1%, 600 mg 35% versus 8.8%.Painful diabetic neuropathy: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (47% vs 42%; RR 1.1 (95% CI 1.01 to 1.2); NNTB 22 (12 to 200); 8 studies, 2320 participants, moderate-quality evidence), more had at least 50% pain intensity reduction (31% vs 24%; RR 1.3 (95% CI 1.2 to 1.5); NNTB 22 (12 to 200); 11 studies, 2931 participants, moderate-quality evidence), and more had PGIC much or very much improved (51% vs 30%; RR 1.8 (95% CI 1.5 to 2.0); NNTB 4.9 (3.8 to 6.9); 5 studies, 1050 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (63% vs 52%; RR 1.2 (95% CI 1.04 to 1.4); NNTB 9.6 (5.5 to 41); 2 studies, 611 participants, low-quality evidence), and more had at least 50% pain intensity reduction (41% vs 28%; RR 1.4 (95% CI 1.2 to 1.7); NNTB 7.8 (5.4 to 14); 5 studies, 1015 participants, low-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 11% versus 3.1%, 600 mg 15% versus 4.5%; dizziness 300 mg 13% versus 3.8%, 600 mg 22% versus 4.4%.Mixed or unclassified post-traumatic neuropathic pain: More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (48% vs 36%; RR 1.2 (1.1 to 1.4); NNTB 8.2 (5.7 to 15); 4 studies, 1367 participants, low-quality evidence), and more had at least 50% pain intensity reduction (34% vs 20%; RR 1.5 (1.2 to 1.9); NNTB 7.2 (5.4 to 11); 4 studies, 1367 participants, moderate-quality evidence). Somnolence (12% vs 3.9%) and dizziness (23% vs 6.2%) were more common with pregabalin.Central neuropathic pain: More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (44% vs 28%; RR 1.6 (1.3 to 2.0); NNTB 5.9 (4.1 to 11); 3 studies, 562 participants, low-quality evidence) and at least 50% pain intensity reduction (26% vs 15%; RR 1.7 (1.2 to 2.3); NNTB 9.8 (6.0 to 28); 3 studies, 562 participants, low-quality evidence). Somnolence (32% vs 11%) and dizziness (23% vs 8.6%) were more common with pregabalin.Other neuropathic pain conditions: Studies show no evidence of benefit for 600 mg pregabalin in HIV neuropathy (2 studies, 674 participants, moderate-quality evidence) and limited evidence of benefit in neuropathic back pain or sciatica, neuropathic cancer pain, or polyneuropathy.Serious adverse events, all conditions: Serious adverse events were no more common with placebo than with pregabalin 300 mg (3.1% vs 2.6%; RR 1.2 (95% CI 0.8 to 1.7); 17 studies, 4112 participants, high-quality evidence) or pregabalin 600 mg (3.4% vs 3.4%; RR 1.1 (95% CI 0.8 to 1.5); 16 studies, 3995 participants, high-quality evidence).
AUTHORS' CONCLUSIONS
Evidence shows efficacy of pregabalin in postherpetic neuralgia, painful diabetic neuralgia, and mixed or unclassified post-traumatic neuropathic pain, and absence of efficacy in HIV neuropathy; evidence of efficacy in central neuropathic pain is inadequate. Some people will derive substantial benefit with pregabalin; more will have moderate benefit, but many will have no benefit or will discontinue treatment. There were no substantial changes since the 2009 review.
Topics: Acute Disease; Adult; Analgesics; Chronic Disease; Diabetic Neuropathies; Dizziness; Humans; Neuralgia; Neuralgia, Postherpetic; Pain; Pregabalin; Randomized Controlled Trials as Topic; Sleepiness
PubMed: 30673120
DOI: 10.1002/14651858.CD007076.pub3 -
Expert Review of Neurotherapeutics Nov 2016The first two alphadelta ligands - gabapentin (GBP) and pregabalin (PGB) - were initially synthesized as antiepileptics; however, they were later also found to be useful... (Review)
Review
The first two alphadelta ligands - gabapentin (GBP) and pregabalin (PGB) - were initially synthesized as antiepileptics; however, they were later also found to be useful for the treatment of additional conditions. Areas covered: Relevant publications describing potential underlying mechanisms, clinical pharmacokinetics/pharmacokinetics, and clinical efficacy and safety of these drugs in various disease conditions were searched in PubMed and Scopus and included in this review. Expert commentary: GBP and PGB are effective for the treatment neuropathic pain, fibromyalgia and epilepsy; in addition, they may be useful for the reduction of postoperative pain. PGB is also effective for the treatment of generalized anxiety disorder and GBP for the treatment of restless legs syndrome. GBP may be considered a treatment option for pain associated with Guillain-Barré Syndrome and phantom limb and for the management of uremic pruritus. Mirogabalin (MGB), recently developed, is being investigated for the treatment of peripheral neuropathic pain and fibromyalgia, showing promising results in patients with diabetic peripheral neuropathy. Their most frequent adverse reactions are of neuropsychiatric nature and include fatigue, dizziness, sedation, somnolence, and ataxia; peripheral edema and weight gain are also frequently described. Pharmacokinetic interactions are scarce; however, pharmacodynamic interactions have been described in association with drugs with CNS-depressant effects.
Topics: Amines; Bridged Bicyclo Compounds; Calcium Channel Blockers; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Ligands; Nervous System Diseases; Pregabalin; gamma-Aminobutyric Acid
PubMed: 27345098
DOI: 10.1080/14737175.2016.1202764 -
Current Pain and Headache Reports Sep 2023Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and... (Review)
Review
PURPOSE OF REVIEW
Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and interventional treatments for postherpetic neuralgia and updates the research on the efficacy, thereby providing doctors with more treatment options. The adverse effects and effective doses of its various treatments are also presented so that the therapy can be prescribed according to their concrete physical conditions. In a word, this review is dedicated to providing a comprehensive overview of the treatment options for postherpetic neuralgia and offering patients more choices.
RECENT FINDINGS
Combinational therapy is more excellent than monotherapy. The local anesthesia and gabapentin comprised outstanding compatibility. In addition, two therapeutic tools for PHN patients, especially for the intractable ones, electroacupuncture (EA), and osteopathic manipulative treatment (OMT), show their efficacy and become potential options to alleviate pain. In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). And drug efficacy can be limited by adverse effects and tolerated doses. Interventional treatments, with their invasiveness and operational difficulty, are usually considered for intractable patients. Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture.
Topics: Humans; Aged; Neuralgia, Postherpetic; Gabapentin; Pregabalin; Antidepressive Agents, Tricyclic; Lidocaine; Analgesics
PubMed: 37493871
DOI: 10.1007/s11916-023-01146-x