DOCSLIB.ORG

Duloxetine with Placebo in the Treatment of Fibromyalgia Patients with Or Without Major Depressive Disorder

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Duloxetine with Placebo in the Treatment of Fibromyalgia Patients with Or Without Major Depressive Disorder ARTHRITIS & RHEUMATISM Vol. 50, No. 9, September 2004, pp 2974–2984 DOI 10.1002/art.20485 © 2004, American College of Rheumatology A Double-Blind, Multicenter Trial Comparing Duloxetine With Placebo in the Treatment of Fibromyalgia Patients With or Without Major Depressive Disorder Lesley M. Arnold,1 Yili Lu,2 Leslie J. Crofford,3 Madelaine Wohlreich,2 Michael J. Detke,4 Smriti Iyengar,2 and David J. Goldstein,5 for the Duloxetine Fibromyalgia Trial Group Objective. To assess the efficacy and safety of Impression of Severity (CGI-Severity) scale, Patient duloxetine, a serotonin and norepinephrine reuptake Global Impression of Improvement (PGI-Improvement) inhibitor, in subjects with primary fibromyalgia, with or scale, Brief Pain Inventory (short form), Medical Out- without current major depressive disorder. comes Study Short Form 36, Quality of Life in Depres- Methods. This study was a randomized, double- sion Scale, and Sheehan Disability Scale. blind, placebo-controlled trial conducted in 18 outpa- Results. Compared with placebo-treated subjects, tient research centers in the US. A total of 207 subjects duloxetine-treated subjects improved significantly more on the FIQ total score, with a treatment (0.027 ؍ meeting the American College of Rheumatology criteria (P ,for primary fibromyalgia were enrolled (89% female, difference of ؊5.53 (95% confidence interval ؊10.43 white, mean age 49 years, 38% with current major ؊0.63), but not significantly more on the FIQ pain score 87% ,Compared with placebo-treated subjects .(0.130 ؍ depressive disorder). After single-blind placebo treat- (P ment for 1 week, subjects were randomly assigned to duloxetine-treated subjects had significantly greater or (104 ؍ receive duloxetine 60 mg twice a day (n reductions in Brief Pain Inventory average pain severity for 12 weeks. Co–primary outcome (103 ؍ placebo (n -Brief Pain Inventory average inter ,(0.008 ؍ score (P measures were the Fibromyalgia Impact Questionnaire number of tender ,(0.004 ؍ ference from pain score (P (FIQ) total score (score range 0–80, with 0 indicating no ,(0.048 ؍ and FIQ stiffness score (P ,(0.002 ؍ points (P impact) and FIQ pain score (score range 0–10). Second- and had significantly greater improvement in mean ary outcome measures included mean tender point pain CGI-Severity ,(0.002 ؍ tender point pain threshold (P threshold, number of tender points, FIQ fatigue, tired- and several ,(0.033 ؍ PGI-Improvement (P ,(0.048 ؍ P) ness on awakening, and stiffness scores, Clinical Global quality-of-life measures. Duloxetine treatment im- Supported by Eli Lilly and Company. proved fibromyalgia symptoms and pain severity re- 1Lesley M. Arnold, MD: University of Cincinnati College of gardless of baseline status of major depressive disorder. ؍ Medicine, Cincinnati, Ohio; 2Yili Lu, PhD, Madelaine Wohlreich, Compared with placebo-treated female subjects (n ؍ ,MD, Smriti Iyengar, PhD: Eli Lilly and Company, Indianapolis Indiana; 3Leslie J. Crofford, MD: University of Michigan, Ann Arbor; 92), duloxetine-treated female subjects (n 92) dem- 4Michael J. Detke, MD, PhD: Indiana University Medical School and onstrated significantly greater improvement on most Eli Lilly and Company, Indianapolis, Indiana, McLean Hospital, efficacy measures, while duloxetine-treated male sub- ؍ -Belmont, Massachusetts, and Harvard Medical School, Boston, Mas sachusetts; 5David J. Goldstein, MD, PhD: Indiana University Medical jects (n 12) failed to improve significantly on any School and PRN Consulting, Indianapolis, Indiana. efficacy measure. The treatment effect on significant Drs. Crofford and Arnold have received consulting fees or pain reduction in female subjects was independent of honoraria in the last 2 years from Eli Lilly and Company (Dr. Crawford Ͻ$10,000, Dr. Arnold Ͼ$10,000). In addition to the authors the effect on mood or anxiety. Duloxetine was safely employed by Eli Lilly and Company listed above, Dr. Goldstein’s wife administered and well tolerated. is employed by Eli Lilly and Company. Conclusion. Address correspondence and reprint requests to Lesley M. In this randomized, controlled, 12- Arnold, MD, University of Cincinnati Medical Arts Building, Suite week trial (with a 1-week placebo lead-in phase), dulox- 8200, 222 Piedmont Avenue, Cincinnati, OH 45219. E-mail: etine was an effective and safe treatment for many of the [email protected]. Submitted for publication July 11, 2003; accepted in revised symptoms associated with fibromyalgia in subjects with form May 26, 2004. or without major depressive disorder, particularly for 2974 DULOXETINE VERSUS PLACEBO IN FIBROMYALGIA 2975 women, who had significant improvement across most persistent and neuropathic pain and found to be effec- outcome measures. tive in reducing pain-related behaviors at doses that did not cause neuromuscular dysfunction (19–21). In these Fibromyalgia is a chronic musculoskeletal pain animal models, duloxetine was more potent than ven- disorder of unknown etiology, characterized by wide- lafaxine, amitriptyline, or desipramine and more effec- spread pain and muscle tenderness, and often accompa- tive than the SSRI paroxetine and the selective NE nied by fatigue, sleep disturbance, and depressed mood inhibitor thionisoxetine in reducing persistent pain- (1,2). Fibromyalgia occurs in ϳ2% of the general pop- related behaviors in animals (20). The findings from ulation in the US and is more common in women than in these preclinical studies suggested that duloxetine might men (3.4% of women and 0.5% of men) (3). There are be an effective treatment for some forms of persistent few reported effective treatments and no Food and Drug pain in humans. Administration–approved treatments for fibromyalgia, Abnormalities in 5-HT and NE neurotransmis- which is associated with substantial morbidity and dis- sion are also involved in the pathophysiology of major ability. depressive disorder, which is frequently comorbid with The pathophysiology of fibromyalgia is unknown, fibromyalgia (1). Patients with major depressive disorder but abnormalities in central monoaminergic neurotrans- commonly present with painful physical symptoms, such mission might play a role. There is evidence of dysfunc- as headache, back pain, stomach aches, and poorly tion in both serotonin (5-hydroxytryptamine [5-HT]) localized musculoskeletal pain, although it is not known and norepinephrine (NE) systems in patients with fibro- whether major depressive disorder is associated with myalgia (4–7). Both 5-HT and NE have also been altered pain processing or whether the pain associated implicated in the mediation of endogenous analgesic with major depressive disorder has an etiology similar to mechanisms via the descending inhibitory pain pathways that of pain in fibromyalgia (22–24). Duloxetine has in the brain and spinal cord (8–10). Dysfunction of been shown to be a safe, tolerable, and effective antide- 5-HT– and NE-mediated descending pain-inhibitory pressant at doses of 60–120 mg/day (25–27). In a previ- pathways is a potential mechanism for the pain experi- ous trial, duloxetine also significantly reduced painful enced by patients with fibromyalgia. Antidepressants physical symptoms associated with major depressive that increase 5-HT– and NE-mediated neurotransmis- disorder (28). sion are commonly used to treat fibromyalgia and other Based on the evidence from preclinical and clin- chronic pain conditions (11). Prior treatment studies ical studies of duloxetine showing potential efficacy in with antidepressant medications suggested that inhibi- tion of both the 5-HT and NE reuptake transporters was the treatment of persistent pain symptoms and the more effective in treating fibromyalgia than inhibition of painful physical symptoms associated with depression, either transporter alone (11,12). Two recent meta-ana- we hypothesized that duloxetine would be safe and lyses of trials of tricyclic medications that inhibit both efficacious in reducing pain severity and the impact of 5-HT and NE reuptake found a consistent, moderate fibromyalgia in patients with or without current major efficacy for these agents (13,14). However, many pa- depressive disorder. To test this hypothesis on behalf of tients with fibromyalgia cannot tolerate the sedative and the Duloxetine Fibromyalgia Trial Group (see Appendix other adverse effects associated with tricyclic agents. As A), we conducted a randomized, placebo-controlled, an alternative to tricyclic agents, selective serotonin double-blind, parallel-group study to assess the safety reuptake inhibitors (SSRIs), which are likely to be better and efficacy of duloxetine, titrated to 60 mg twice a day, tolerated, have had mixed results in treatment studies of in 207 outpatients meeting the American College of fibromyalgia (12,15–18). Rheumatology (ACR) criteria for fibromyalgia (2) with Duloxetine hydrochloride is a potent 5-HT and or without current major depressive disorder. The dose NE reuptake inhibitor (SNRI) that is relatively evenly of 120 mg/day was selected based on results of a previous balanced with similar affinity for both 5-HT and NE clinical trial of fibromyalgia suggesting that patients reuptake inhibition. Duloxetine lacks significant affinity might respond better to higher doses of antidepressants ␣ for muscarinic, histamine 1, 1-adrenergic, dopamine, (16). This is one of the largest clinical trials ever 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, and opi- conducted for the treatment of fibromyalgia, and, to our oid receptors. Because of the proposed role of 5-HT
Load more

Recommended publications
  • Pregabalin Is First Drug Approved for Fibromyalgia
    50 Pain Medicine C LINICAL P SYCHIATRY N EWS • August 2007 Pregabalin Is First Drug Approved for Fibromyalgia BY ELIZABETH MECHCATIE that are not usually painful, and that pre- cording to the revised prescribing infor- The daily dose should be administered Senior Writer gabalin may reduce the degree of pain ex- mation for pregabalin. The two studies— in two divided doses per day, starting at a perienced by patients with fibromyalgia by a 14-week double-blind placebo-controlled total daily dose of 150 mg/day, which regabalin has become the first drug binding to a specific protein within study and a 6-month randomized with- may be increased to 300 mg/day, within 1 to win approval by the Food and “overexcited nerve cells.” drawal study—found that treatment was week; the maximum dose is 450 mg/day, PDrug Administration for the man- The approval “marks an important ad- associated with a reduction in pain by vi- according to the prescribing information. agement of fibromyalgia. vance, and provides a reason for optimism sual analog scale and improvements based The most common side effects in the tri- The FDA based the approval on two for the many patients on a patient global as- als were mild to moderate dizziness and double-blind, controlled trials of approxi- who will receive pain Side effects such as sessment and on the sleepiness, blurred vision, weight gain, dry mately 1,800 patients. Data from the stud- relief ” with prega- Fibromyalgia Impact mouth, and swelling of the hands and feet ies have shown that patients with fi- balin, Dr.
    [Show full text]
  • Intravenous Ketamine Alleviates Pain in a Rheumatoid Arthritis Patient with Comorbid Fibromyalgia
    Case Report J Med Cases. 2018;9(5):142-144 Intravenous Ketamine Alleviates Pain in a Rheumatoid Arthritis Patient With Comorbid Fibromyalgia Ashraf F. Hannaa, b, Bishoy Abrahama, Andrew Hannaa, Micheal McKennaa, Adam J. Smitha Abstract bance, and psychological distress [4]. It is commonly regarded as the “prototypical central sensitivity syndrome” [5]. While A 49-year-old woman with rheumatoid arthritis (RA) and comorbid its etiology is not fully understood, fibromyalgia is thought to fibromyalgia presented to the clinic in extreme pain, described to be result from abnormal central pain processing and increased a 10 on an 11-point pain intensity numerical rating scale (PI-NRS). central sensitivity that results in intense, widespread pain. Fi- Because the patient also met the diagnostic criteria for fibromyalgia bromyalgia is diagnosed using the 2010 American College of and conventional medications did not achieve adequate pain control Rheumatology (ACR) criteria [6]: 1) Widespread pain index for either condition, the off-label use of intravenous (IV) ketamine (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5 or WPI was presented as an alternative therapeutic option. The patient un- 3 - 6 and SS scale score ≥ 9. 2) Symptoms have been present derwent 10 consecutive IV infusion sessions with increasing doses at a similar level for at least 3 months. 3) The patient does not of ketamine hydrochloride without any complications. Following the have a disorder that would otherwise explain the pain. 10th infusion, the patient reported that her pain was virtually non- A recent epidemiological study characterized the preva- existent (PI-NRS 0 - 1). lence of fibromyalgia among patients without pain, with re- gional pain, and with widespread pain [4].
    [Show full text]
  • Ketamine for Chronic Non- Cancer Pain: a Review of Clinical Effectiveness, Cost- Effectiveness, And
    CADTH RAPID RESPONSE REPORT: SUMMARY WITH CRITICAL APPRAISAL Ketamine for Chronic Non- Cancer Pain: A Review of Clinical Effectiveness, Cost- Effectiveness, and Guidelines Service Line: Rapid Response Service Version: 1.0 Publication Date: May 28, 2020 Report Length: 28 Pages Authors: Khai Tran, Suzanne McCormack Cite As: Ketamine for Chronic Non-Cancer Pain: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Ottawa: CADTH; 2020 May. (CADTH rapid response report: summary with critical appraisal) ISSN: 1922-8147 (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document.
    [Show full text]
  • Pubmed/19078481?Dopt=Abstract
    Efficacy of tramadol in treatment of pain in fibromyalgia. - Pu... https://www.ncbi.nlm.nih.gov/pubmed/19078481?dopt=Abstract PubMed Format: Abstract J Clin Rheumatol. 2000 Oct;6(5):250-7. Efficacy of tramadol in treatment of pain in fibromyalgia. Russell IJ1, Kamin M, Bennett RM, Schnitzer TJ, Green JA, Katz WA. Author information Abstract An outpatient, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy and safety of tramadol in the treatment of the pain of fibromyalgia syndrome. One hundred patients with fibromyalgia syndrome, (1990 American College of Rheumatology criteria), were enrolled into an open-label phase and treated with tramadol 50-400 mg/day. Patients who tolerated tramadol and perceived benefit were randomized to treatment with tramadol or placebo in the double-blind phase. The primary efficacy outcome measurement was the time (days) to exit from the double-blind phase because of inadequate pain relief, which was reported as the cumulative probability of discontinuing treatment because of inadequate pain relief. One hundred patients entered the open-label phase; 69% tolerated and achieved benefit with tramadol. These patients were then randomized to continue tramadol (n = 35) or convert to a placebo (n = 34) during a 6-week, double-blind treatment period. The Kaplan-Meier estimate of cumulative probability of discontinuing the double blind period because of inadequate pain relief was significantly lower in the tramadol group compared with the placebo group (p = 0.001). Twenty (57.1%) patients in the tramadol group successfully completed the entire double-blind phase compared with nine (27%) in the placebo group (p = .015).
    [Show full text]
  • Therapeutic Class Overview Neuropathic Pain and Fibromyalgia Agents
    Therapeutic Class Overview Neuropathic Pain and Fibromyalgia Agents INTRODUCTION • Neuropathic pain is commonly described by patients as burning or electrical in nature and results from injury or damage to the nervous system (Herndon et al 2017). Management of neuropathic pain may prove challenging due to unpredictable patient response to drug therapy (Attal et al 2010). • Fibromyalgia is characterized by chronic musculoskeletal pain with unknown etiology and pathophysiology. Patients typically complain of widespread musculoskeletal pain, fatigue, cognitive disturbance, psychiatric symptoms, and multiple somatic symptoms (Goldenberg 2019). Fibromyalgia is often difficult to treat and requires a multidisciplinary, individualized treatment program (Goldenberg 2018). • This review focuses on medications that are approved by the Food and Drug Administration (FDA) for the treatment of fibromyalgia, neuropathic pain, and/or post-herpetic neuralgia (PHN). The products in this review include Cymbalta (duloxetine), Gralise (gabapentin ER), Horizant (gabapentin enacarbil ER), Lidoderm (lidocaine 5% patch), Lyrica (pregabalin), Lyrica CR (pregabalin ER), Neurontin (gabapentin), Nucynta ER (tapentadol ER), Qutenza (capsaicin), Savella (milnacipran), and ZTlido (lidocaine 1.8% topical system). These agents represent a variety of pharmacologic classes, including anticonvulsants, serotonin-norepinephrine reuptake inhibitors (SNRIs), extended-release (ER) opioids, and topical analgesics. As such, these agents hold additional FDA-approved indications
    [Show full text]
  • Corporate Medical Policy Nerve Fiber Density Testing AHS – M2112 “Notification”
    Corporate Medical Policy Nerve Fiber Density Testing AHS – M2112 “Notification” File Name: nerve_fiber_density_testing Origination: 01/01/2019 Last CAP Review: n/a Next CAP Review: 01/01/2020 Last Review: 01/01/2019 Policy Effective April 1, 2019 Description of Procedure or Service Nerve fiber density testing involves analysis of skin biopsy stained with an antibody to antiprotein gene product 9.5 (Wilkinson et al., 1989) which avidly stains all axons (Dalsgaard, Rydh, & Haegerstrand, 1989). The number and morphology of axons within the epidermis are evaluated to determine epidermal nerve fiber density (McCarthy et al., 1995) and assess for the presence and degree of neuropathy (A. G. Smith & Gibson, 2018). ***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician. Policy BCBSNC will provide coverage for nerve fiber density testing when it is determined to be medically necessary because the medical criteria and guidelines shown below are met. Benefits Application This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy. When nerve fiber density testing is covered Skin biopsy with epidermal nerve fiber density measurement for the diagnosis of small-fiber neuropathy
    [Show full text]
  • Fibromyalgia
    Fibromyalgia SANGITA CHAKRABARTY, MD, MSPH, Meharry Medical College, Nashville, Tennessee ROGER ZOOROB, MD, MPH, Meharry Medical College and Vanderbilt University, Nashville, Tennessee Fibromyalgia is an idiopathic, chronic, nonarticular pain syndrome with generalized tender points. It is a multisystem disease characterized by sleep disturbance, fatigue, headache, morning stiffness, paresthesias, and anxiety. Nearly 2 percent of the general population in the United States suffers from fibromyalgia, with females of middle age being at increased risk. The diagnosis is primarily based on the presence of widespread pain for a period of at least three months and the presence of 11 tender points among 18 specific anatomic sites. There are certain comorbid con- ditions that overlap with, and also may be confused with, fibromyalgia. Recently there has been improved recognition and understanding of fibromyalgia. Although there are no guidelines for treatment, there is evidence that a multidimensional approach with patient education, cognitive behavior therapy, exercise, physical therapy, and pharmacologic therapy can be effective. (Am Fam Physician 2007;76:247-54. Copyright © 2007 American Academy of Family Physicians.) This article exemplifies ibromyalgia is an idiopathic, chronic, gesting the contribution of both genetic and the AAFP 2007 Annual nonarticular pain syndrome defined environmental factors.4 Clinical Focus on manage- ment of chronic illness. by widespread musculoskeletal Demographic and social characteristics ▲ pain and generalized tender points associated with the presence of fibromyalgia See editorial on F(Table 1). Other common symptoms include are female sex, being divorced, failing to com- page 290. ▲ sleep disturbances, fatigue, headache, morning plete high school, and low income. Psycho- Patient information: Handouts on fibromyalgia stiffness, paresthesias, and anxiety.
    [Show full text]
  • The Journal of Rheumatology Volume 75, No. Is Fibromyalgia a Neuropathic Pain Syndrome?
    The Journal of Rheumatology Volume 75, no. Is fibromyalgia a neuropathic pain syndrome? Michael C Rowbotham J Rheumatol 2005;75;38-40 http://www.jrheum.org/content/75/38 1. Sign up for TOCs and other alerts http://www.jrheum.org/alerts 2. Information on Subscriptions http://jrheum.com/faq 3. Information on permissions/orders of reprints http://jrheum.com/reprints_permissions The Journal of Rheumatology is a monthly international serial edited by Earl D. Silverman featuring research articles on clinical subjects from scientists working in rheumatology and related fields. Downloaded from www.jrheum.org on September 24, 2021 - Published by The Journal of Rheumatology Is Fibromyalgia a Neuropathic Pain Syndrome? MICHAEL C. ROWBOTHAM ABSTRACT. The fibromyalgia syndrome (FM) seems an unlikely candidate for classification as a neuropathic pain. The disorder is diagnosed based on a compatible history and the presence of multiple areas of musculoskeletal tenderness. A consistent pathology in either the peripheral or central nervous system (CNS) has not been demonstrated in patients with FM, and they are not at higher risk for diseases of the CNS such as multiple sclerosis or of the peripheral nervous system such as peripheral neuropathy. A large proportion of FM suf- ferers have accompanying symptoms and signs of uncertain etiology, such as chronic fatigue, sleep distur- bance, and bowel/bladder irritability. With the exception of migraine headaches and possibly irritable bowel syndrome, the accompanying disorders are clearly not neurological in origin. The impetus to classify the FM as a neuropathic pain comes from multiple lines of research suggesting widespread pain and tenderness are associated with chronic sensitization of the CNS.
    [Show full text]
  • Fibromyalgia
    The Voice of the Patient A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative Fibromyalgia Public Meeting: March 26, 2014 Report Date: October 2014 Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA) Table of Contents Introduction ......................................................................................................................................3 Meeting overview ..................................................................................................................................... 3 Report overview and key themes ............................................................................................................. 4 Topic 1: Disease Symptoms and Daily Impacts That Matter Most to Patients .......................................5 Perspectives on most significant symptoms ............................................................................................. 6 Overall impact of fibromyalgia on daily life .............................................................................................. 8 Topic 2: Patient Perspectives on Treatments for Fibromyalgia .............................................................9 Prescriptions and over-the-counter drugs ................................................................................................ 9 Non-drug therapies ................................................................................................................................
    [Show full text]
  • Amitriptyline Information Booklet
    Drug information Amitriptyline AMITRIPTYLINE is used to relieve pain in several long-term conditions including arthritis, back pain and fibromyalgia Amitriptyline information booklet Introduction • arthritis (arth-rye-tus) • back pain Amitriptyline (a-muh-trip-tuh-leen) is a drug that can reduce your • fibromyalgia (fie-bruh-my-al-juh) pain and discomfort, and help you get a good night’s sleep. • tension headaches and migraines You can discuss the benefits and risks of taking amitriptyline with • damage to nerve endings in limbs, which may be described to healthcare professionals before you start treatment, so you’re able you as peripheral neuropathy (pe-rif-er-ul new-ro-pa-thee). to make an informed decision. You may not be able to take amitriptyline if: What is amitriptyline and how is it used? • you’ve had an allergic reaction to a medication in the past • you have heart problems, as it can make them worse Amitriptyline is a type of drug called a tricyclic antidepressant. • you have uncontrolled bipolar disorder These drugs were originally developed to treat anxiety and depression, but when taken at a low dose they can reduce or • you have the rare inherent blood disorder porphyria stop pain. (por-fear-ee-ya) which affects the nervous system • you have liver or kidney problems Amitriptyline works by increasing the amount of serotonin your • you have epilepsy, as it can increase the risk of seizures brain makes. Serotonin is a chemical, called a neurotransmitter, that • you’ve had or are having treatment for depression, as some the brain sends out to nerves in the body.
    [Show full text]
  • Milnacipran, a Serotonin and Norepinephrine Reuptake Inhibitor: a Novel Treatment for Fibromyalgia
    Drug Evaluation Milnacipran, a serotonin and norepinephrine reuptake inhibitor: a novel treatment for fibromyalgia Milnacipran hydrochloride is a serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor that was recently approved by the US FDA for the treatment of fibromyalgia (FM). Evidence has accumulated suggesting that, in animal models, milnacipran may exert pain-mitigating influences involving norepinephrine- and serotonin-related processes at supraspinal, spinal and peripheral levels in pain transmission. Milnacipran has demonstrated efficacy for the reduction of pain as well as improvements in global assessments of well-being and functional capacity among treated FM patients. Its role in addressing comorbidities associated with FM, including visceral pain and migraine, has, as yet, to be investigated. Milnacipran may be of special interest for use in patients for whom hepatic dysfunction precludes the use of other agents, for example, duloxetine. It has a negligible influence on cytochrome metabolism, and therefore may be of particular benefit in patients requiring multiple concurrently prescribed medications. Milnacipran may comprise a reasonable option in the armamentarium of treatments available to manage FM. KEYWORDS: antidepressants n chronic pain n fibromyalgian milnacipran n serotonin Raphael J Leo and norepinephrine reuptake inhibitor Department of Psychiatry, School of Medicine and Fibromyalgia (FM) is a syndrome characterized Several pharmacological approaches have Biomedical Sciences, by chronic, widespread musculoskeletal pain and been advocated for the treatment of FM. State University of New York at tenderness. The prevalence of FM in the general Because of their impact on these presump- Buffalo, Erie County Medical population is estimated to be 2–4%; it tends to tive pathophysiologic processes, antidepres- Center, 462 Grider Street, show a female predilection, and increases with sants have frequently been advocated for Buffalo, NY 14215, USA age [1,2].
    [Show full text]
  • Beyond Depression: Other Uses for Tricyclic Antidepressants
    REVIEW Joanne Schneider, DNP, RN, CNP Mary Patterson, CNP Xavier F. Jimenez, MD, MA Center for Comprehensive Pain Recovery, Center for Comprehensive Pain Recovery, Center for Comprehensive Pain Recovery, Neurological Institute, Cleveland Clinic Neurological Institute, Cleveland Clinic Neurological Institute, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH Beyond depression: Other uses for tricyclic antidepressants ABSTRACT ost tricyclic antidepressants (TCAs) M have US Food and Drug Administration Tricyclic antidepressants (TCAs) were originally designed approval for treatment of depression and anxi- and marketed for treating depression, but over time they ety disorders, but they are also a viable off-label have been applied to a variety of conditions, mostly off- option that should be considered by clinicians label. TCAs can serve as first-line or augmenting drugs in specialties beyond psychiatry, especially for for neuropathic pain, headache, migraine, gastrointesti- treating pain syndromes. Given the ongoing nal syndromes, fibromyalgia, pelvic pain, insomnia, and epidemic of opioid use disorder, increasing atten- psychiatric conditions other than depression. This article tion has been drawn to alternative strategies for reviews pharmacology, dosing, and safety considerations chronic pain management, renewing an interest for these uses. in the use of TCAs. This review summarizes the pharmacologic KEY POINTS properties of TCAs, their potential indications Amitriptyline is the most useful TCA for many painful in conditions other than depression, and safety conditions. considerations. ■ BRIEF HISTORY OF TRICYCLICS TCAs can be especially helpful for patients with a pain syndrome or insomnia with comorbid depression, al- TCAs were originally designed in the 1950s and marketed later for treating depression.
    [Show full text]