|
1
|
Barbosa EC, Ortegal GHPC, de Andrade LS, Costa MR, Santos AMS. Efficacy and safety of preoperative duloxetine in reducing post-laparoscopic surgery pain: a meta-analysis of randomized placebo-controlled trials. Int J Clin Pharm 2025; 47:294-303. [PMID: 39812914 DOI: 10.1007/s11096-024-01855-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 12/09/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Recent studies suggest that duloxetine administration before non-laparoscopic surgery may reduce postoperative pain and analgesic requirement without increasing adverse event occurrence. AIM To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) on preoperative administration of duloxetine versus placebo for postoperative pain relief in adults undergoing laparoscopic surgery, assessing efficacy- and safety-related outcomes. METHOD We systematically searched MEDLINE, Embase, and Cochrane Library, covering all records up to July 19, 2024. Inclusion criteria consisted of RCTs comparing preoperative administration of duloxetine versus placebo in adults undergoing laparoscopic surgery and reporting at least one outcome of interest. The random-effects model was used to estimate the mean difference (MD) and risk ratio (RR), along with their respective 95% confidence intervals (95%CIs). RESULTS We included four RCTs (227 patients). Compared with placebo, duloxetine provided a statistically lower pain scores at 2 (MD - 1.04; 95%CI - 1.75, - 0.33), 4 (MD - 1.28; 95%CI - 1.77, - 0.79), 8 (MD - 1.22; 95%CI - 1.72, - 0.72), 12 (MD - 1.64; 95%CI - 2.88, - 0.41), and 24 h (MD - 1.05; 95%CI - 1.72, - 0.39) after surgery. Duloxetine also granted a statistically longer time to first analgesic requirement (MD 128.38 min; 95%CI 41.31, 215.46), compared with placebo. Additionally, the duloxetine group had a significantly lower risk of nausea/vomiting (RR 0.48; 95%CI 0.25, 0.90), while there were no significant differences between both groups for the risk of dizziness, headache, and somnolence. CONCLUSION Compared with placebo, duloxetine administration before laparoscopic surgery significantly minimized postoperative pain intensity, delayed analgesic requirement, and reduced nausea/vomiting risk.
Collapse
Affiliation(s)
- Eduardo Cerchi Barbosa
- Department of Medicine, Evangelical University of Goiás, Avenida Universitária Km 3.5, Cidade Universitária, Anápolis, GO, 75083-515, Brazil.
| | | | - Lucas Santos de Andrade
- Department of Medicine, Evangelical University of Goiás, Avenida Universitária Km 3.5, Cidade Universitária, Anápolis, GO, 75083-515, Brazil
| | - Milena Rodrigues Costa
- Department of Medicine, Evangelical University of Goiás, Avenida Universitária Km 3.5, Cidade Universitária, Anápolis, GO, 75083-515, Brazil
| | - Andreia Moreira Silva Santos
- Department of Medicine, Evangelical University of Goiás, Avenida Universitária Km 3.5, Cidade Universitária, Anápolis, GO, 75083-515, Brazil
| |
Collapse
|
|
2
|
Çıracıoğlu AM, Armağan O, Uslu S, Berkan F, Özgen M, Dal Erdoğan S, Çolak E. Vitamin K levels in Fibromyalgia Syndrome Patients and Their Associations with Pain, Disease Activity, Quality of Life and Inflammatory Cytokines. Pain Manag Nurs 2023; 24:60-67. [PMID: 36057510 DOI: 10.1016/j.pmn.2022.07.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 07/24/2022] [Accepted: 07/31/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND Fibromyalgia syndrome (FMS) is a chronic pain condition that requires multidisciplinary treatment. Vitamin K is an antioxidant that plays a role in many reactions in the body, and its effectiveness in FMS has not been studied before. AIM We aimed to evaluate vitamin K levels in FMS patients and their relationship with pain, disease activity, quality of life, and inflammatory cytokines. METHOD Eighty-eight female patients with FMS and 87 controls were included in the study. Vitamin K and inflammatory cytokine (interleukin-6 [IL-6], IL-8, tumor necrosis factor [TNF]-alfa) serum levels were measured in both groups. Visual Analog Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), and Short Form-36 (SF-36) scales were used. RESULTS No statistically significant differences in vitamin K levels between the two groups, and no relationships were found between these levels and pain, FIQ, SF-36, and inflammatory cytokines (p > .05). While IL-6 and TNF-alpha levels were found to be high in the FMS group compared with the control group (p < .05), no difference in IL-8 levels was noted (p > .05). In the FMS group, positive correlations were found between IL-6 and FIQ, and between TNF-alpha and physical role difficulty(p > .05). CONCLUSIONS Overall, the results of this study do not provide any evidence of an association between FMS and vitamin K levels. However, high IL-6 and TNF-alpha levels suggest that low-intensity inflammation may accompany FMS and have a negative impact on physical activity. Future studies are needed to determine the relationship between vitamin K and FMS.
Collapse
Affiliation(s)
- Ayşe Merve Çıracıoğlu
- Department of Physical Medicine and Rehabilitation, Tavşanlı Doç. Dr. Mustafa Kalemli Hospital, Kütahya, Turkey.
| | - Onur Armağan
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
| | - Sema Uslu
- Department of Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
| | - Funda Berkan
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
| | - Merih Özgen
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
| | - Suheyla Dal Erdoğan
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
| | - Ertuğrul Çolak
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
| |
Collapse
|
|
3
|
AlOmair M, AlMalki H, Sarhan L, Shweel M, Asiri A, Almhjani E, Asiri A, AlQahtani H, Rahman A, Hasan E. Fibromyalgia Concomitant with Seropositive Rheumatoid Arthritis in a Tertiary Hospital in South-Western Saudi Arabia: Prevalence and Treatment Patterns. Open Rheumatol J 2022. [DOI: 10.2174/18743129-v16-e2209290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Introduction:
Rheumatoid arthritis (RA) patients with fibromyalgia syndrome (FMS) report worse functional status and quality of life hence the association has important clinical implications. FMS can be challenging to treat, and the current evidence recommends a multidisciplinary treatment approach focused on symptom management.
Aim:
Information regarding the current prevalence of FMS in RA patients is lacking. Thus, this study aims to address the prevalence and predictors of FMS in seropositive RA patients and demonstrate our clinical practice in the management of FMS.
Methods:
Participants’ data was gathered from Aseer central hospital (ACH) rheumatology clinics and daycare units over a period of 2 years. Subjects were assessed using the 2010 American College of Rheumatology (ACR) criteria for FMS. Data were collected from medical records, including patient demographics, comorbidities and concomitant FMS-related data.
Results:
Out of 310 seropositive RA patients, 15% (n = 47) fulfilled the diagnostic criteria for FMS. Of them, 29, 11 and 7 were on pregabalin, amitriptyline and duloxetine, respectively. Half of FMS patients showed one or more therapy changes. A significant difference between RA patients with and without concomitant FMS was observed, including age, gender and comorbidities.
Conclusion:
In this retrospective study, a high prevalence of FMS in individuals with seropositive RA was identified. This study explores real-world practice in the treatment of FMS with remarkable findings regarding underdosing and lower discontinuation rate of pregabalin.
Collapse
|
|
4
|
Abstract
Fibromyalgia (FM) is a condition of chronic widespread pain (CWP) that can occur throughout the life cycle and is likely underrecognized in older patients. FM is associated with considerable suffering and reduction in quality of life and may occur as a unique condition, but in older patients is most likely to be associated with another medical illness. Understood mechanistically to be a sensitization of the nervous system, recently identified as nociplastic pain, FM is accepted as a valid medical illness that requires a positive diagnosis and directed treatments. The cornerstone of treatments for FM are nonpharmacologic interventions, with the understanding that medications provide only modest benefit for most patients, and with particular concern about adverse effects in older patients. If FM is not recognized, treatments may be misdirected to the other medical condition, with failure to address FM symptoms, leading to overall poor outcome. In contrast, new complaints in older patients should not immediately be attributed to FM, and physicians should be vigilant to ensure that onset of a new illness is not ignored. As FM is most often a lifelong condition, patients should be encouraged to identify their own personal strategies that can attenuate symptoms, especially when symptoms flare. Continued life participation should be the outcome goal.
Collapse
Affiliation(s)
- Amir Minerbi
- Institute for Pain Medicine, Rambam Health Campus, Haifa, Israel.,Ruth and Bruce Rapaport Faculty of Medicine, Technion, Haifa, Israel
| | - Mary-Ann Fitzcharles
- Alan Edwards Pain Management Unit, McGill University Health Centre, Montreal General Hospital, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada. .,Division of Rheumatology, McGill University Health Centre, Montreal, QC, Canada.
| |
Collapse
|
|
5
|
Upadhyaya HP, Arnold LM, Alaka K, Qiao M, Williams D, Mehta R. Efficacy and safety of duloxetine versus placebo in adolescents with juvenile fibromyalgia: results from a randomized controlled trial. Pediatr Rheumatol Online J 2019; 17:27. [PMID: 31138224 PMCID: PMC6540374 DOI: 10.1186/s12969-019-0325-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 04/30/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Currently, there are no medications approved for the treatment of juvenile fibromyalgia (JFM). We evaluated the safety and efficacy of duloxetine 30/60 mg once daily (QD) versus placebo in adolescents with JFM. METHODS In this Phase 3b, multisite (US, Argentina, Puerto Rico, and India) trial, patients aged 13-17 years with JFM and a score of ≥4 on the Brief Pain Inventory-Modified Short Form: Adolescent Version (BPI) 24-h average pain severity score were randomized to duloxetine or placebo for the 13-week double-blind period. The starting duloxetine dose was 30 mg, with a target dose of 60 mg QD, as tolerated. The primary endpoint was the mean change in 24-h average pain severity of the Brief Pain Inventory (BPI) from baseline to Week 13, analyzed using mixed-model repeated measures (MMRM) technique. Secondary measures were BPI severity and interference scores; treatment response (≥30%, ≥50% reductions on BPI average pain severity); Pediatric Pain Questionnaire; Clinical Global Impression of Severity: Overall and Mental Illness scales; Functional Disability Inventory: child and parent versions; Children's Depression Inventory; Multidimensional Anxiety Scale for Children; and safety and tolerability. Continuous secondary efficacy measures were analyzed using analysis of covariance or MMRM, and categorical data using Cochran-Mantel-Haenszel test and Fisher's exact test, where appropriate. RESULTS A total of 184 patients with JFM received duloxetine (N = 91) or placebo (N = 93), of which 149 patients (81.0%) completed the 13-week double-blind treatment period. Baseline characteristics were comparable between groups; majority of the patients were Caucasian (77.17%) and females (75.0%), with a mean age of 15.53 years. For the primary measure, BPI average pain severity, the mean change was not statistically different between duloxetine and placebo (- 1.62 vs. -0.97, respectively; p = .052). For secondary efficacy outcomes, statistically significantly more duloxetine- versus placebo-treated patients had a treatment response (≥30% and ≥50% reductions on BPI average pain severity) and improvement of the general activity and relationships items on the BPI interference subscale. The percentage of patients reporting at least 1 treatment-emergent adverse event was higher in the duloxetine versus placebo groups (82.42% vs. 62.37%, respectively; p = .003). The overall safety profile of duloxetine in this study was similar to that reported previously in duloxetine pediatric trials of other indications. CONCLUSIONS The primary study outcome, mean change in 24-h BPI average pain severity rating from baseline to Week 13, did not significantly improve with duloxetine compared to placebo in patients with JFM. However, significantly more patients on duloxetine compared to placebo had a ≥30% and ≥50% reduction in pain severity. There were no new safety concerns related to duloxetine in the study population. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01237587 . Registered 08 November, /2010.
Collapse
Affiliation(s)
- Himanshu P. Upadhyaya
- 0000 0000 2220 2544grid.417540.3Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 USA
| | - Lesley M. Arnold
- 0000 0001 2179 9593grid.24827.3bUniversity of Cincinnati College of Medicine, Cincinnati, OH USA
| | - Karla Alaka
- 0000 0000 2220 2544grid.417540.3Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 USA
| | | | | | - Renata Mehta
- Focus Clinical Consulting Inc, Toronto, ON Canada
| |
Collapse
|
|
6
|
Najafi A, Zeinali Nejad H, Nikvarz N. Evaluation of the analgesic effects of duloxetine in burn patients: An open-label randomized controlled trial. Burns 2019; 45:598-609. [DOI: 10.1016/j.burns.2018.10.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 10/07/2018] [Accepted: 10/17/2018] [Indexed: 12/22/2022]
|
|
7
|
Stinson J, Connelly M, Kamper SJ, Herlin T, Toupin April K. Models of Care for addressing chronic musculoskeletal pain and health in children and adolescents. Best Pract Res Clin Rheumatol 2017; 30:468-482. [PMID: 27886942 DOI: 10.1016/j.berh.2016.08.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 08/03/2016] [Accepted: 08/08/2016] [Indexed: 12/22/2022]
Abstract
Chronic musculoskeletal pain among children and adolescents is common and can negatively affect quality of life. It also represents a high burden on the health system. Effective models of care for addressing the prevention and management of pediatric musculoskeletal pain are imperative. This chapter will address the following key questions: (1) Why are pediatric-specific models of pain care needed? (2) What is the burden of chronic musculoskeletal pain among children and adolescents? (3) What are the best practice approaches for early identification and prevention of chronic musculoskeletal pain in children and adolescents? (4) What are the recommended strategies for clinical management of chronic pain, including pharmacological, physical, psychological and complementary, and alternative approaches? (5) What are the most effective strategies for implementing models of pain care across different care settings? (6) What are the research priorities to improve models of care for children and adolescents with chronic musculoskeletal pain?
Collapse
Affiliation(s)
- Jennifer Stinson
- The Hospital for Sick Children, Lawrence S. Bloomberg, Faculty of Nursing, University of Toronto, Peter Gilgan Centre for Research and Learning, 686 Bay Street, Room 069715, Toronto, ON, M5G 0A4, Canada.
| | - Mark Connelly
- Division of Developmental and Behavioral Sciences, The Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA.
| | - Steven J Kamper
- The George Institute, University of Sydney, PO Box M201 Missenden Rd, Camperdown, NSW 2050 Australia.
| | - Troels Herlin
- Department of Pediatrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark.
| | - Karine Toupin April
- Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada; Department of Pediatrics, Faculty of Medicine, University of Ottawa, 401 Smyth Road Ottawa, Ontario, K1H 8L1, Canada.
| |
Collapse
|
|
8
|
Telles-Correia D, Barbosa A, Cortez-Pinto H, Campos C, Rocha NBF, Machado S. Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity. World J Gastrointest Pharmacol Ther 2017; 8:26-38. [PMID: 28217372 PMCID: PMC5292604 DOI: 10.4292/wjgpt.v8.i1.26] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 11/02/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first-pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity.
Collapse
|
|
9
|
Konno S, Oda N, Ochiai T, Alev L. Randomized, Double-blind, Placebo-controlled Phase III Trial of Duloxetine Monotherapy in Japanese Patients With Chronic Low Back Pain. Spine (Phila Pa 1976) 2016; 41:1709-1717. [PMID: 27831985 PMCID: PMC5113250 DOI: 10.1097/brs.0000000000001707] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 04/28/2016] [Accepted: 05/11/2016] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN A 14-week, randomized, double-blind, multicenter, placebo-controlled study of Japanese patients with chronic low back pain (CLBP) who were randomized to either duloxetine 60 mg once daily or placebo. OBJECTIVE This study aimed to assess the efficacy and safety of duloxetine monotherapy in Japanese patients with CLBP. SUMMARY OF BACKGROUND DATA In Japan, duloxetine is approved for the treatment of depression, diabetic neuropathic pain, and pain associated with fibromyalgia; however, no clinical study of duloxetine has been conducted for CLBP. METHODS The primary efficacy measure was the change in the Brief Pain Inventory (BPI) average pain score from baseline to Week 14. Secondary efficacy measures included BPI pain (worst pain, least pain, pain right now), Patient's Global Impression of Improvement, Clinical Global Impressions of Severity, and Roland-Morris Disability Questionnaire, among other measures, and safety and tolerability. RESULTS In total, 458 patients were randomized to receive either duloxetine (n = 232) or placebo (n = 226). The BPI average pain score improved significantly in the duloxetine group compared with that in the placebo group at Week 14 [-2.43 ± 0.11 vs. -1.96 ± 0.11, respectively; between-group difference (95% confidence interval), - 0.46 [-0.77 to-0.16]; P = 0.0026]. The duloxetine group showed significant improvement in many secondary measures compared with the placebo group, including BPI pain (least pain, pain right now) (between-group difference: -1.69 ± 0.10, P = 0.0009; -2.42 ± 0.12, P P = 0.0230, respectively), Patient's Global Impression of Improvement (2.46 ± 0.07, P = 0.0026), Clinical Global Impressions of Severity (-1.46 ± 0.06, P = 0.0019), and Roland-Morris Disability Questionnaire (-3.86 ± 0.22, P = 0.0439). Adverse events occurring at a significantly higher incidence in the duloxetine group were somnolence, constipation, nausea, dizziness, and dry mouth, most of which were mild or moderate in severity and were resolved or improved. CONCLUSION Duloxetine 60 mg was effective and well tolerated in Japanese CLBP patients. LEVEL OF EVIDENCE 2.
Collapse
Affiliation(s)
- Shinichi Konno
- Department of Orthopedic Surgery, Fukushima Medical University, Fukushima, Japan
| | | | | | - Levent Alev
- Medicines Development Unit, Medical Science, Eli Lilly Japan K.K., Kobe, Japan
| |
Collapse
|
|
10
|
Murakami M, Osada K, Ichibayashi H, Mizuno H, Ochiai T, Ishida M, Alev L, Nishioka K. An open-label, long-term, phase III extension trial of duloxetine in Japanese patients with fibromyalgia. Mod Rheumatol 2016; 27:688-695. [PMID: 27796152 DOI: 10.1080/14397595.2016.1245237] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES We aimed to evaluate the long-term safety and efficacy of duloxetine 60 mg in Japanese patients with fibromyalgia enrolled from a preceding randomized, placebo-controlled, phase III duloxetine trial. METHODS This was a long-term, open-label extension study. Patients received oral duloxetine once daily at a dose of 20 mg for 1 week, followed by 40 mg for 1 week, and then 60 mg for 48 weeks. The primary outcome was the frequency of adverse events (AEs) and adverse drug reactions (ADRs) of duloxetine. Efficacy and health outcomes were assessed. RESULTS In total, 149 patients were enrolled from the preceding study. The median length of treatment was 364.0 days. The incidence of AEs and ADRs was 92.6 and 63.8%, respectively. ADRs occurring at an incidence of ≥5% were somnolence, constipation, nausea, weight increase, thirst, and malaise. The proportion of patients with mild, moderate, and severe AEs was 80.5, 10.1, and 2.0%. There were no serious treatment-related AEs in this study. The Brief Pain Inventory average pain score improved at all time-points compared with baseline (mean change ± standard deviation at Week 50 was -1.31 ± 1.70). CONCLUSIONS Duloxetine was safe and effective in the long-term treatment of Japanese patients with fibromyalgia.
Collapse
Affiliation(s)
- Masato Murakami
- a Department of Psychosomatic Medicine , Nihon University School of Medicine , Tokyo , Japan
| | - Kenichi Osada
- b Department of Neuropsychiatry , St. Marianna University School of Medicine , Kawasaki , Japan
| | | | | | | | | | | | - Kusuki Nishioka
- e Institute of Medical Science , Tokyo Medical University , Tokyo , Japan
| |
Collapse
|
|
11
|
Liu Y, Qian C, Yang M. Treatment Patterns Associated with ACR-Recommended Medications in the Management of Fibromyalgia in the United States. J Manag Care Spec Pharm 2016; 22:263-71. [PMID: 27003556 PMCID: PMC10398128 DOI: 10.18553/jmcp.2016.22.3.263] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Fibromyalgia (FM) affects up to 6% of U.S. adults, resulting in a significant burden on the health care system and poor quality of life for patients. Duloxetine, pregabalin, and milnacipran are approved for management of FM; however, consensus is lacking regarding optimal therapy. Patients with FM taking approved medications often do not experience meaningful symptom relief, and many experience intolerable adverse events. OBJECTIVE To assess treatment patterns associated with available and commonly used medications for the management of FM using U.S. health insurance claims. METHODS This retrospective analysis used the MarketScan claims database to identify adults with a first diagnosis of FM (ICD-9-CM code 729.1) between 2009 and 2011 with continuous health plan enrollment for 12 months pre- and post-index. Medications of interest were pregabalin, gabapentin, duloxetine, milnacipran, cyclobenzaprine, and tramadol. These are 6 of the 8 medications recommended by the American College of Rheumatology (ACR) for treating FM; the other 2 (amitriptyline and venlafaxine) were only included in some initial assessments. The Charlson Comorbidity Index (CCI) was used to assess overall comorbidity burden. Endpoints included proportion of patients treated within 1 year after first diagnosis; initial treatment pattern; adherence over the first-year follow-up period for the medications of interest; and discontinuation, switching, and combination therapy patterns among pain medications of interest at different time points. Proportion of days covered (PDC; defined as number of days in the period when the patient had drug supply divided by the number of days in the period) was used to define adherence, which was categorized as low (PDC < 50%), medium (PDC 50% to < 80%), or high (PDC ≥ 80%). The time to discontinuation (defined as the first drug supply gap ≥ 90 days) was estimated using Kaplan-Meier analysis. RESULTS Overall, 240,144 patients met the inclusion criteria. Patients were predominantly women (68%), had preferred provider organization insurance coverage (68%), and had a CCI score < 1 at baseline (69%). Only 31% (n = 74,738) initiated a treatment with a prescription medication listed in the ACR guidelines, and many patients received less than the recommended dose. Most (n = 70,919) patients initially received monotherapy with one of the 8 prescription medications. Of those who started with ≥ 2 medications (n = 3,819), cyclobenzaprine plus tramadol was the most frequent combination. Adherence was suboptimal for all 6 medications of interest. Duloxetine had the highest mean PDC (59%); for all other agents, mean PDC was < 50%. With the exception of duloxetine, discontinuation rates at 6 months were > 50% for all agents. Alterations in therapy were common. Among patients who discontinued their initial treatment of duloxetine, pregabalin, or milnacipran, approximately one-third had switched treatments within 90 days after their first prescription. For those who maintained their initial treatment agent, approximately 50% of patients added a second pain medication within 1 year of treatment initiation. CONCLUSIONS The evidence suggests that patients with FM often do not receive 1 of the prescription medications recommended by ACR guidelines, and those who do are commonly prescribed lower-than-recommended doses, potentially resulting in poor effectiveness and tolerability. Discontinuation, switching, and addition of new pain medications are common, which may indicate low levels of satisfaction with initial treatment. New therapies with improved effectiveness and better tolerability are urgently needed for patients with FM.
Collapse
Affiliation(s)
- Yifei Liu
- Associate Professor, Division of Pharmacy Practice and Administration, University of Missouri—Kansas City School of Pharmacy, Kansas City, Missouri
| | - Chunlin Qian
- Associate Director, Health Economics and Outcomes Research, Daiichi Sankyo, Parsippany, New Jersey
| | - Mei Yang
- Associate Director, Health Economics and Outcomes Research, Daiichi Sankyo, Parsippany, New Jersey
| |
Collapse
|
|
12
|
Murakami M, Osada K, Mizuno H, Ochiai T, Alev L, Nishioka K. A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese fibromyalgia patients. Arthritis Res Ther 2015; 17:224. [PMID: 26296539 PMCID: PMC4546310 DOI: 10.1186/s13075-015-0718-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Accepted: 07/16/2015] [Indexed: 12/01/2022] Open
Abstract
Introduction Fibromyalgia is characterized by widespread pain and is often accompanied by accessory symptoms. There are limited treatment options for this condition in Japan. Therefore, we conducted a phase III study to assess the efficacy and safety of duloxetine in Japanese patients with fibromyalgia. Methods This randomized, double-blind, placebo-controlled, parallel-group trial was conducted in Japan. Outpatients who met the American College of Rheumatology 1990 criteria for fibromyalgia and whose Brief Pain Inventory (BPI) average pain score was ≥4 were randomized to duloxetine 60 mg or placebo once daily for 14 weeks. The primary efficacy measure was the change in the BPI average pain score from baseline. Secondary efficacy, quality of life (QoL), and safety outcomes were also evaluated. Mixed-effects model repeated-measures (MMRM) analysis and last observation carried forward (LOCF) analysis of covariance were used to evaluate the primary efficacy measure. Results Overall, 393 patients were randomized to receive either duloxetine (n = 196) or placebo (n = 197). The MMRM analysis revealed no significant difference between duloxetine and placebo regarding the change in BPI average pain scores at week 14. Based on LOCF analysis, a statistically significant improvement in the change in BPI average pain scores at week 14 was observed for patients treated with duloxetine compared with placebo. Duloxetine treatment was associated with improved outcomes in nearly all secondary and post hoc analyses. The treatment was generally well tolerated. Somnolence, nausea, and constipation were the most common treatment-emergent adverse events in the duloxetine group. The discontinuation rates due to treatment-emergent adverse events were similar in both groups. Conclusions Although the MMRM analysis did not demonstrate superiority of duloxetine over placebo, duloxetine treatment was associated with improved outcomes in secondary and post hoc analyses of the mean change in the BPI average pain score and most of the secondary outcomes, including analgesia and QoL. Duloxetine treatment was safe and well tolerated. These results suggest that duloxetine treatment could be associated with improvements in pain relief and QoL in Japanese patients with fibromyalgia. Trial registration ClinicalTrials.gov Identifier: NCT01552057. Registered 9 March 2012.
Collapse
Affiliation(s)
- Masato Murakami
- Department of Psychosomatic Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.
| | - Kenichi Osada
- Department of Neuropsychiatry, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan.
| | - Hiromichi Mizuno
- Shionogi & Co. Ltd., 12F, Hankyu Terminal Bldg, 1-4 Shibata 1-chome, Kita-ku, Osaka, 530-0012, Japan.
| | - Toshimitsu Ochiai
- Shionogi & Co. Ltd., 12F, Hankyu Terminal Bldg, 1-4 Shibata 1-chome, Kita-ku, Osaka, 530-0012, Japan.
| | - Levent Alev
- Eli Lilly Japan K.K., Sannomiya Plaza Building, 7-1-5 Isogamidori, Chuo-ku, Kobe, 651-0086, Japan.
| | - Kusuki Nishioka
- Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
| |
Collapse
|
|
13
|
A randomized, placebo-controlled, double-blinded trial of duloxetine in the treatment of general fatigue in patients with chronic fatigue syndrome. PSYCHOSOMATICS 2014; 56:242-53. [PMID: 25660434 DOI: 10.1016/j.psym.2014.12.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2014] [Revised: 12/11/2014] [Accepted: 12/11/2014] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome. METHODS A 12-week, randomized, double-blind study was designed to compare duloxetine 60-120 mg/d (n = 30) with placebo (n = 30) for efficacy and safety in the treatment of patients with chronic fatigue syndrome. The primary outcome measure was the Multidimensional Fatigue Inventory general fatigue subscale (range: 4-20, with higher scores indicating greater fatigue). Secondary measures were the remaining Multidimensional Fatigue Inventory subscales, Brief Pain Inventory, Medical Outcomes Study Short Form-36, Hospital Anxiety and Depression Scale, Centers for Disease Control and Prevention Symptom Inventory, Patient Global Impression of Improvement, and Clinical Global Impression of Severity. The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the measure of effect. RESULTS The improvement in the Multidimensional Fatigue Inventory general fatigue scores for the duloxetine group was not significantly greater than for the placebo group (P = 0.23; estimated difference between groups at week 12 = -1.0 [95% CI: -2.8, 0.7]). The duloxetine group was significantly superior to the placebo group on the Multidimensional Fatigue Inventory mental fatigue score, Brief Pain Inventory average pain severity and interference scores, Short Form-36 bodily pain domain, and Clinical Global Impression of Severity score. Duloxetine was generally well tolerated. CONCLUSION The primary efficacy measure of general fatigue did not significantly improve with duloxetine when compared with placebo. Significant improvement in secondary measures of mental fatigue, pain, and global measure of severity suggests that duloxetine may be efficacious for some chronic fatigue syndrome symptom domains, but larger controlled trials are needed to confirm these results.
Collapse
|
|
14
|
VanderWeide LA, Smith SM, Trinkley KE. A systematic review of the efficacy of venlafaxine for the treatment of fibromyalgia. J Clin Pharm Ther 2014; 40:1-6. [DOI: 10.1111/jcpt.12216] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2014] [Accepted: 09/10/2014] [Indexed: 12/20/2022]
Affiliation(s)
- L. A. VanderWeide
- Department of Clinical Pharmacy; University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences; Aurora CO USA
- Department of Pharmacy; The Ohio State University Wexner Medical Center; Columbus OH USA
| | - S. M. Smith
- Departments of Pharmacotherapy & Translational Research and Community Health & Family Medicine; Colleges of Pharmacy and Medicine; University of Florida; Gainesville FL USA
| | - K. E. Trinkley
- Department of Clinical Pharmacy; University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences; Aurora CO USA
| |
Collapse
|
|
15
|
|
|
16
|
Abstract
Fibromyalgia is a chronic pain condition present in 2-4% of the population. Fibromyalgia consists of widespread pain with similarities to neuropathic pain in clinical findings, pathophysiology, and neuropharmacology. Pain is the predominant symptom and allodynia and hyperalgesia are common signs. Extreme fatigue, impaired cognition and nonrestorative sleep difficulties coexist in addition to other somatic symptoms. Research including neuroimaging investigations shows abnormalities in neurotransmitters and an abnormal response to pain. Altered pain processing peripherally and centrally contribute to central sensitization and a dampened effect of the diffuse noxious inhibitory control (DNIC). Successful management incorporates education of the patient in self-management skills, cognitive behavioral therapy (CBT), exercise, and drug therapy. Tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs) (duloxetine and milnacipran), α2-δ ligands (gabapentin and pregabalin) are effective in reducing pain by≥30%. Some success has been shown with dopamine agonists (pramipexole), tramadol, other opioids and cannabinoids (nabilone). Further evidence-based trials using complementary treatments are needed. Fibromyalgia is complex and requires a multidisciplinary approach to treatment. Patient self-management is key.
Collapse
Affiliation(s)
- Janice E Sumpton
- Department of Pharmacy, Victoria Hospital, London Health Sciences Centre, London, Ontario, Canada.
| | - Dwight E Moulin
- Departments of Clinical Neurological Sciences and Oncology, University of Western Ontario, London, Ontario
| |
Collapse
|
|
17
|
Effectiveness of Duloxetine for the Treatment of Chronic Nonorganic Orofacial Pain. Clin Neuropharmacol 2012; 35:273-7. [DOI: 10.1097/wnf.0b013e31827453fa] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
18
|
|
|
19
|
Abstract
Duloxetine is a serotonin and norepinephrine reuptake inhibitor, which is mainly used to treat depression. This retrospective study describes the demographic and clinical effects of duloxetine ingestions reported to the National Poison Data System (NPDS). NPDS data were searched for duloxetine exposures between 2004 and 2010. A total of 11,373 patients were included and exposures were divided into three groups of ages ≤6 years old, 7–12 years and >12 years. Neurological clinical effects occurred in 6.1% of the patients aged ≤6 years, 13.0% of the patients aged 7–12 years and 24.6% of the patients aged >12 years. Cardiovascular effects occurred in 1.4% of the patients aged ≤6 years old, 2.5% of the patients aged 7–12 years and 11.6% of the patients aged >12 years. Gastrointestinal effects occurred in 4.1% of the patients aged ≤6 years old, 16.6% of the patients aged 7–12 years and 13.8% of the patients aged >12 years. Tachycardia, nausea, vomiting, agitation/irritability, dizziness/vertigo and drowsiness were among the most common clinical effects in all three groups. Overall, 61.4% of the patients aged ≤6 years and 77.5% of the patients aged 7–12 years were managed in a non–health care facility, while 55.8% of the patients aged >12 years were referred to or already in a health care facility. We conclude that the majority of ingestions are benign in both pediatrics and adults. Most symptomatic patients have neurologic, gastrointestinal and cardiovascular effects. Most pediatric patients will be able to be managed in a non–health care facility.
Collapse
Affiliation(s)
- J Jacob
- Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA
| | - D Albert
- Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA
| | - K Heard
- Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA
| |
Collapse
|
|
20
|
Bennett R, Russell IJ, Choy E, Spaeth M, Mease P, Kajdasz D, Walker D, Wang F, Chappell A. Evaluation of Patient-Rated Stiffness Associated With Fibromyalgia: A Post-Hoc Analysis of 4 Pooled, Randomized Clinical Trials of Duloxetine. Clin Ther 2012; 34:824-37. [DOI: 10.1016/j.clinthera.2012.02.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2011] [Revised: 02/15/2012] [Accepted: 02/15/2012] [Indexed: 12/13/2022]
|
|
21
|
Abstract
Fibromyalgia is a syndrome characterized by chronic generalized pain associated with different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems, hypersensitivity to physical and psychological environmental stimuli, depression and anxiety. It has been estimated to affect roughly the 2-4% of the general population in most countries studied, and it has been shown to be much more prevalent in women than in men. Although its pathophysiology is not yet fully understood, it is known that both genetic and environmental factors are involved in its development. Fibromyalgia shares a high degree of co-morbidity with other conditions, including chronic headache, temporomandibular disorder, irritable bowel syndrome, major depression, anxiety disorders and chronic fatigue syndrome. Therefore, this is a syndrome difficult to treat for which multimodal treatments including physical exercise, psychological therapies and pharmacological treatment are recommended. Although different kinds of drugs have been studied for the treatment of fibromyalgia, the most widely used drugs that have the higher degree of evidence for efficacy include the α(2)δ ligands pregabalin and gabapentin, and the tricyclic antidepressants (TCAs) and serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). However, there is a need to look for newer additional therapeutic pharmacological options for the treatment of this complex and disabling disease. First- and second-generation antipsychotics have shown analgesic properties both in an experimental setting and in humans, although most of the available evidence for the treatment of human pain concerns older antipsychotics and involves clinical trials performed several decades ago. In addition, several second-generation antipsychotics, risperidone, olanzapine and quetiapine, have shown efficacy in the treatment of some anxiety disorders. Some second-generation antipsychotics, mainly quetiapine, aripiprazole and amisulpride, have demonstrated antidepressant activity, with quetiapine approved for the treatment of bipolar depression and refractory major depression, and aripiprazole approved as an adjunctive treatment for major depressive disorder. Finally, several old and new antipsychotics, including promethazine, levopromazine, olanzapine, quetiapine and ziprasidone, have been shown to improve sleep parameters in healthy subjects. Each of these properties suggests that antipsychotics could represent a new potential alternative for the treatment of fibromyalgia syndrome. To date, most of the published studies on the use of antipsychotics in the treatment of fibromyalgia syndrome have been uncontrolled, either case reports or case series, dealing with olanzapine, quetiapine, ziprasidone, levopromazine and amisulpride. The studies on olanzapine and quetiapine have suggested therapeutic efficacy although, in the case of olanzapine, hampered by tolerability problems. A double-blind controlled trial, published in 1980, showed that chlorpromazine increased slow-wave sleep and improved pain and mood disturbances. More recently, four double-blind controlled studies have explored the efficacy of quetiapine, either alone or as an add-on treatment, in fibromyalgia management. None of these trials has yet been published, although two of them have been presented as congress communications, both of them suggesting that quetiapine could be a potential alternative treatment for fibromyalgia. In summary, the current available evidence suggests that at least some antipsychotics, specifically quetiapine, could be useful for the treatment of fibromyalgia and that further studies on the efficacy of these compounds are worth pursuing.
Collapse
Affiliation(s)
- Elena P Calandre
- Institute of Neuroscience and Center for Biomedical Investigations, University of Granada, Granada, Spain.
| | | |
Collapse
|
|
22
|
HOCHBERG MARCC, WOHLREICH MADELAINE, GAYNOR PAULA, HANNA SYLVIA, RISSER RICK. Clinically Relevant Outcomes Based on Analysis of Pooled Data from 2 Trials of Duloxetine in Patients with Knee Osteoarthritis. J Rheumatol 2011; 39:352-8. [DOI: 10.3899/jrheum.110307] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Objective.To determine response with duloxetine versus placebo in patients with osteoarthritis (OA) of the knee using the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responder index and other clinically relevant outcomes including minimal clinically important improvement (MCII) and patient acceptable symptom state (PASS) for pain and function.Methods.Data were pooled from two 13-week, randomized, double-blind, placebo-controlled trials comparing duloxetine 60 to 120 mg/day with placebo in patients with symptomatic OA of the knee. Treatment response was determined according to the OMERACT-OARSI responder index, ≥ 30% pain reduction, ≥ 50% pain reduction, and MCII and PASS for pain and function. (ClinicalTrials.gov identifiers NCT00433290 and NCT00408421)Results.Duloxetine-treated patients were 33% more likely to experience an OMERACT-OARSI response than placebo-treated patients [p < 0.001, number needed to treat (NNT) = 6]. A significantly greater percentage of duloxetine-treated patients, compared with placebo-treated patients, reported ≥ 30% improvement in pain from baseline to endpoint (p < 0.001, NNT = 5) and ≥ 50% improvement in pain relative to baseline (p < 0.001, NNT = 7). The duloxetine-treated patients were also more likely to fulfill MCII criteria for pain (p < 0.001, NNT = 6) and function (p < 0.001, NNT = 7), and to achieve PASS for pain (p < 0.001, NNT = 6) and function (p = 0.009, NNT = 9). More duloxetine-treated patients compared with placebo-treated patients experienced ≥ 1 treatment-emergent adverse event (p = 0.003, number needed to harm = 8).Conclusion.Significantly more patients receiving duloxetine than placebo achieved an OMERACT-OARSI response, improvements in pain and function exceeding the level accepted as MCII, and reached PASS. Results support the clinical relevance of outcomes of prior duloxetine studies in symptomatic OA of the knee.
Collapse
|
|
23
|
|
|
24
|
Beard SM, Roskell N, Le TK, Zhao Y, Coleman A, Ang D, Lawson K. Cost effectiveness of duloxetine in the treatment of fibromyalgia in the United States. J Med Econ 2011; 14:463-476. [PMID: 21651426 DOI: 10.3111/13696998.2011.586389] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To evaluate the cost effectiveness of duloxetine when considered as an alternative treatment for patients in the United States (US) being treated for fibromyalgia pain. RESEARCH DESIGN AND METHODS A Markov model was used to evaluate the economic and clinical advantages of duloxetine in controlling fibromyalgia pain symptoms over a 2-year time horizon. A base-case treatment sequence was adopted from clinical guidelines, based on tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, anticonvulsants, and opioids. Treatment response was modeled using changes from baseline in pain severity, and response thresholds: full response (at least a 50% change), response (30-49% change), and no response (less than a 30% change). Clinical efficacy and discontinuation data were taken from placebo- and active-controlled trials identified in a systematic literature review and mixed-treatment comparison. Utility data were based on EQ-5D data. MAIN OUTCOME MEASURES Additional symptom-control months (SCMs), defined as the amount of time at a response level of 30% or less, and quality-adjusted life-years (QALYs) over a 2-year time horizon. RESULTS For every 1000 patients, first-line duloxetine resulted in an additional 665 SCMs and 12.3 QALYs, at a cost of $582,911 (equivalent to incremental cost-effectiveness ratios [ICERs] of $877 per SCM and $47,560 per QALY). Second-line duloxetine resulted in an additional 460 SCMs and 8.7 QALYs, at a cost of $143,752 (equivalent to ICERs of $312 per SMC and $16,565 per QALY). LIMITATIONS Response data for TCAs are limited to 30% improvement levels, reported trials are small, and have low placebo response rates. The model necessarily assumes that response rates are independent of placement in the treatment sequence. CONCLUSIONS The results suggest that the introduction of duloxetine into the standard treatment sequence for fibromyalgia not only provides additional patient benefits, reflected by time spent in pain control, but also is cost effective when compared with commonly adopted thresholds.
Collapse
Affiliation(s)
- S M Beard
- RTI Health Solutions, Manchester, UK.
| | | | | | | | | | | | | |
Collapse
|
|
25
|
Smith HS, Bracken D, Smith JM. Pharmacotherapy for fibromyalgia. Front Pharmacol 2011; 2:17. [PMID: 21772818 PMCID: PMC3131797 DOI: 10.3389/fphar.2011.00017] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2010] [Accepted: 03/09/2011] [Indexed: 12/27/2022] Open
Abstract
Fibromyalgia (FM) is a chronic disorder characterized by multifocal pain and other associated somatic symptoms including fatigue, insomnia, cognitive/memory problems, and even psychological distress. It appears that 2–4% of the general population suffers from FM. FM negatively impacts the physical functioning of its patients, as evidenced by difficulties with multiple daily activities, as well as affecting emotional health, social functioning, and health related quality of life. This review will discuss the potential theories that possibly contribute to the pathogenesis of FM, although the precise mechanism is unknown. The evolution of the assessment of FM will also be examined, with the waning use of tender point examinations and the appearance of new simple, practical diagnostic criteria. Although non-pharmacologic therapeutic options (exercise, education, cognitive–behavioral therapy) have been shown to be extremely effective in FM, the focus of this article will be on pharmacologic strategies. Non-Food and Drug Administration (FDA) approved as well as FDA approved agents will be presented. Each agent's therapeutic “niche” in FM management will be discussed based on its pharmacologic profile, patient responsiveness, and tolerability. Finally a clinical algorithm will be presented for the step-wise management of pain and other associated symptoms of FM.
Collapse
Affiliation(s)
- Howard S Smith
- Department of Anesthesiology, Albany Medical College Albany, NY, USA
| | | | | |
Collapse
|
|
26
|
Mease PJ, Walker DJ, Alaka K. Evaluation of duloxetine for chronic pain conditions. Pain Manag 2011; 1:159-70. [DOI: 10.2217/pmt.11.4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Summary Duloxetine hydrochloride (duloxetine) is used as a nonopioid analgesic for the treatment of certain chronic pain conditions. It is a serotonin and norepinephrine reuptake inhibitor and has been approved in the USA for the management of both diabetic peripheral neuropathic pain and fibromyalgia. In addition, based on several studies demonstrating that duloxetine was efficacious in the management of chronic low back pain and chronic pain caused by osteoarthritis, duloxetine was approved for the management of chronic musculoskeletal pain. Effect sizes in studies of each of the aforementioned chronic pain conditions are comparable with other commonly used pain medications. Treatment-emergent adverse events are generally mild to moderate in severity, and tend to occur early and transiently.
Collapse
Affiliation(s)
- Philip J Mease
- Swedish Medical Center & University of Washington School of Medicine, Seattle, WA, USA; Seattle Rheumatology Associates, 1101 Madison Street, Suite 1000, Seattle, WA 98104, USA
| | | | - Karla Alaka
- Lilly Research Laboratories, Indianapolis, IN, USA
| |
Collapse
|
|
27
|
Abstract
This article presents a brief review of the physiologic abnormalities seen in fibromyalgia, current theories of widespread pain, and treatment options, including emerging therapeutics, with a focus on the use of duloxetine to manage fibromyalgia symptoms. Major clinical trials that examine the efficacy and effectiveness of duloxetine to date are reviewed, and safety issues are discussed.
Collapse
Affiliation(s)
- Cheryl L Wright
- Oregon Health and Science University, School of Nursing, Portland, OR 97239, USA.
| | | | | | | |
Collapse
|
|
28
|
Bradley LA, Bennett R, Russell IJ, Wohlreich MM, Chappell AS, Wang F, D'Souza DN, Moldofsky H. Effect of duloxetine in patients with fibromyalgia: tiredness subgroups. Arthritis Res Ther 2010; 12:R141. [PMID: 20630058 PMCID: PMC2945033 DOI: 10.1186/ar3081] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2009] [Revised: 12/01/2010] [Accepted: 07/14/2010] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION This study tested the hypothesis that baseline ratings of fatigue/tiredness would be negatively associated with the efficacy of duloxetine on measures of pain and functional ability in patients with fibromyalgia. METHODS A post hoc analysis of pooled data from 4 double-blind, placebo-controlled studies of duloxetine in fibromyalgia was performed. The fibromyalgia impact questionnaire (FIQ) tiredness item score (0 to 10 scale) was used to define tiredness subgroups. Patients were stratified into 3 subgroups: mild (0 to 3), moderate (4 to 6), and severe (7 to 10) tiredness. Analysis of covariance models and logistic regressions were used to test treatment-by-tiredness subgroup interactions. RESULTS Data from the first 3 months are included in this post hoc analysis (duloxetine N = 797, placebo N = 535). At baseline, the distribution of tiredness severity in the duloxetine and placebo groups respectively was 3.64% and 3.75% mild, 16.71% and 15.57% moderate, and 79.65% and 80.68% severe. Rates of clinically significant (≥30% and ≥50%) improvement in brief pain inventory (BPI) average pain were similar across the tiredness subgroups. Tiredness severity at baseline was not negatively associated with the effects of duloxetine on patients' reports of functional ability using the FIQ total score, FIQ measures of physical impairment, interference with work, pain, stiffness, and depression and the medical outcomes study short form-36 (SF-36). CONCLUSIONS Studies of duloxetine in fibromyalgia have demonstrated clinically significant improvements in pain and functional ability (FIQ, SF-36). This post hoc analysis of data shows that the efficacy of duloxetine among patients with fibromyalgia does not vary as a function of baseline ratings of fatigue/tiredness.
Collapse
Affiliation(s)
- Laurence A Bradley
- Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama 35294, USA.
| | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Comparative Efficacy and Harms of Duloxetine, Milnacipran, and Pregabalin in Fibromyalgia Syndrome. THE JOURNAL OF PAIN 2010; 11:505-21. [PMID: 20418173 DOI: 10.1016/j.jpain.2010.01.002] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2009] [Revised: 08/01/2009] [Accepted: 09/16/2009] [Indexed: 01/17/2023]
|
|
30
|
Abstract
Fibromyalgia is a chronic pain disorder characterized by widespread pain, stiffness, insomnia, fatigue and distress. Several randomized controlled trials (RCTs) have shown moderate effectiveness of pharmacological therapies for fibromyalgia pain. Evidence from these trials suggests that pharmacological therapy can not only improve pain but also fatigue, function and well-being in patients with fibromyalgia. Duloxetine and milnacipran, two highly selective serotonin-norepinephrine (noradrenaline) reuptake inhibitors, and the alpha(2)delta agonist pregabalin have been approved by the US FDA for the treatment of fibromyalgia symptoms. In general, about half of all treated patients seem to experience a 30% reduction of symptoms, suggesting that many patients with fibromyalgia will require additional therapies. Thus, other forms of treatment, including exercise, cognitive behavioural therapies and self-management strategies, may be necessary to achieve satisfactory treatment outcomes. Despite promising results of pilot trials, RCTs with dopamine receptor agonists and sodium channel antagonists have so far been disappointing for patients with fibromyalgia. However, new pharmacological approaches for the treatment of fibromyalgia pain and insomnia using sodium oxybate appear to be promising.
Collapse
Affiliation(s)
- Roland Staud
- Department of Medicine, University of Florida, College of Medicine, Gainesville, Florida 32610-0221, USA.
| |
Collapse
|
|
31
|
Schnitzer TJ. New pharmacologic approaches in the management of osteoarthritis. Arthritis Care Res (Hoboken) 2010; 62:1174-80. [DOI: 10.1002/acr.20260] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
|
|
32
|
Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2010. [DOI: 10.1002/pds.1847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
|
|
33
|
Smith HS, Bracken D, Smith JM. Duloxetine: a review of its safety and efficacy in the management of fibromyalgia syndrome. J Cent Nerv Syst Dis 2010; 2:57-72. [PMID: 23861632 PMCID: PMC3661232 DOI: 10.4137/jcnsd.s4127] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Fibromyalgia (FM) is a chronic disorder characterized by widespread pain and other associated symptoms including fatigue, insomnia, cognitive/memory problems, and even psychological distress. Duloxetine is one of three FDA approved medications (the other two being milnacipran and pregabalin) for the treatment of FM. It has been demonstrated that FM patients possess low central nervous system levels of serotonin and norepinephrine. Duloxetine, which is classified pharmacologically as a serotonin-norepinephrine reuptake inhibitor (SNRI), may be beneficial for FM patients by increasing these levels. This review will touch briefly upon the pathophysiology of FM, diagnostic tools, currently available therapeutic options (both pharmacologic and non-pharmacologic), as well as the pharmacokinetic/pharmacodynamic properties of duloxetine. In addition, the efficacy and safety/tolerability of duloxetine exclusively in FM will be assessed through examination of 5 randomized controlled trials, as well as pooled analyses of current data. Suggestions for a therapeutic niche for duloxetine in FM are discussed based on a presentation of the characteristics of duloxetine.
Collapse
Affiliation(s)
- Howard S Smith
- Albany Medical College, Department of Anesthesiology, Albany, New York 12208, USA
| | | | | |
Collapse
|