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Bagherifard A, Hosseinzadeh A, Koosha F, Sheibani M, Karimi-Behnagh A, Reiter RJ, Mehrzadi S. Melatonin and bone-related diseases: an updated mechanistic overview of current evidence and future prospects. Osteoporos Int 2023; 34:1677-1701. [PMID: 37393580 DOI: 10.1007/s00198-023-06836-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 06/16/2023] [Indexed: 07/04/2023]
Abstract
PURPOSE Bone diseases account for an enormous cost burden on health systems. Bone disorders are considered as age-dependent diseases. The aging of world population has encouraged scientists to further explore the most effective preventive modalities and therapeutic strategies to overcome and reduce the high cost of bone disorders. Herein, we review the current evidence of melatonin's therapeutic effects on bone-related diseases. METHODS This review summarized evidences from in vitro, in vivo, and clinical studies regarding the effects of melatonin on bone-related diseases, with a focus on the molecular mechanisms. Electronically, Scopus and MEDLINE®/PubMed databases were searched for articles published on melatonin and bone-related diseases from inception to June 2023. RESULTS The findings demonstrated that melatonin has beneficial effect in bone- and cartilage-related disorders such as osteoporosis, bone fracture healing, osteoarthritis, and rheumatoid arthritis, in addition to the control of sleep and circadian rhythms. CONCLUSION A number of animal and clinical studies have indicated that various biological effects of melatonin may suggest this molecule as an effective therapeutic agent for controlling, diminishing, or suppressing bone-related disorders. Therefore, further clinical studies are required to clarify whether melatonin can be effective in patients with bone-related diseases.
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Affiliation(s)
- Abolfazl Bagherifard
- Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Azam Hosseinzadeh
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Fereshteh Koosha
- Department of Radiology Technology, Faculty of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Sheibani
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Russel J Reiter
- Department of Cellular and Structural Biology, Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA
| | - Saeed Mehrzadi
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Qi JS, Su Q, Li T, Liu GW, Zhang YL, Guo JH, Wang ZJ, Wu MN. Agomelatine: a potential novel approach for the treatment of memory disorder in neurodegenerative disease. Neural Regen Res 2023; 18:727-733. [DOI: 10.4103/1673-5374.353479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Mahdavi SM, Shariati B, Shalbafan M, Rashedi V, Yarahmadi M, Ghaznavi A, Amiri S. The effectiveness of pregabalin with or without agomelatine in the treatment of chronic low back pain: a double-blind, placebo-controlled, randomized clinical trial. BMC Pharmacol Toxicol 2022; 23:70. [PMID: 36104745 PMCID: PMC9476640 DOI: 10.1186/s40360-022-00612-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 07/27/2022] [Accepted: 09/06/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Although various pharmacological and nonpharmacological treatments are available for the chronic low back pain (CLBP), there is no consensus on the best optimal treatment for this condition. This study aimed to investigate the efficacy of co-administration of pregabalin and agomelatine versus pregabalin with placebo to treat CLBP. METHODS Forty-six CLBP patients without the surgical indication referred to the outpatient orthopedic clinic of Rasoul-e-Akram Hospital, Tehran, Iran, were randomly divided into two study groups: Group A [pregabalin (75 mg twice per day) + placebo] and Group B [pregabalin (75 mg twice per day) + agomelatine (25 mg per night)]. Patients were evaluated at weeks 0, 4, and 8. Outcome measures were the Persian versions of the Brief Pain Inventory (BPI) interference scale, Roland-Morris Disability Questionnaire (RMDQ), The Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Survey (SF-36), and General Health Questionnaire-28 (GHQ-28) were used. RESULTS At weeks 4 and 8 after the intervention, all evaluated measures showed significant improvement in both study groups (P < 0.01). The mean improvement of GHQ-28 was 3.7 ± 1.22 in group A and 13.1 ± 4.71 in group B. This difference was statistically significant (P = 0.003). Other outcomes did not vary substantially between the two research groups. Agomelatine treatment was well tolerated, with no significant adverse effects seen in patients. Liver tests of all patients were routine during the study period. Major adverse effect was not seen in any patient. The prevalence of Minor side effects was not significantly different between two study groups. CONCLUSION Compared with the pregabalin and placebo, co-administration of pregabalin and agomelatine had no added effect on improving pain scores in CLBP patients. However, the patients' general health was significantly improved after the combined administration of pregabalin and agomelatine. TRIAL REGISTRATION The study protocol was registered in the Iranian Registry of Clinical Trials before starting the study (NO.IRCT20200620047852N1, Registration date: 23/06/2020).
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Affiliation(s)
- Seyed Mani Mahdavi
- Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Behnam Shariati
- Mental Health Research Center, Department of Psychiatry, School of Medicine, Psychosocial Health Research Institute (PHRI), Iran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Shalbafan
- Mental Health Research Center, Department of Psychiatry, School of Medicine, Psychosocial Health Research Institute (PHRI), Iran University of Medical Sciences, Tehran, Iran
| | - Vahid Rashedi
- Iranian Research Center on Aging, Department of Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Masoomeh Yarahmadi
- School of Behavioral Sciences and Mental Health, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Ghaznavi
- Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shayan Amiri
- Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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De Stefano R, Bruno A, Muscatello MRA, Cedro C, Cicciù A, Rullo R, Gaeta M, Fiorillo L. Oral Health and Fibromyalgia Syndrome: A Systemic Review. J Funct Morphol Kinesiol 2020; 5:E7. [PMID: 33467223 PMCID: PMC7739237 DOI: 10.3390/jfmk5010007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 01/13/2020] [Accepted: 01/17/2020] [Indexed: 12/12/2022] Open
Abstract
Fibromyalgia is a syndrome currently considered idiopathic and multifactorial rheumatic that causes an increase in muscle tension and is characterized by muscle pain and chronic fibrous tissues-widespread, fluctuating and migrating-associated with stiffness, asthenia, cognitive disorders, insomnia or sleep disorders, alterations in sensitivity to stimuli. In affected patients, there may be anxiety or depressive disorder development. The aim of this study is, with the help of an interdisciplinary team, to evaluate the correlations between this syndrome and oral health. A literature review was conducted, analyzing the most common scientific databases, more than 200 studies were obtained. Subsequently to the application of filters and revision by the authors, only 18 articles were considered eligible for this review. From the results, it is clear that the correlations between fibromyalgia and oral health mainly concern pain in the oro-maxillofacial district, especially in the temporomandibular joint. This certainly could help for faster diagnosis of the syndrome, which is currently difficult to identify.
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Affiliation(s)
- Rosa De Stefano
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, 98100 Messina ME, Italy; (R.D.S.); (A.B.); (M.R.A.M.); (C.C.); (M.G.)
| | - Antonio Bruno
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, 98100 Messina ME, Italy; (R.D.S.); (A.B.); (M.R.A.M.); (C.C.); (M.G.)
| | - Maria Rosaria Anna Muscatello
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, 98100 Messina ME, Italy; (R.D.S.); (A.B.); (M.R.A.M.); (C.C.); (M.G.)
| | - Clemente Cedro
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, 98100 Messina ME, Italy; (R.D.S.); (A.B.); (M.R.A.M.); (C.C.); (M.G.)
| | - Alessandra Cicciù
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, School of Dentistry, University of Messina, 98100 Messina ME, Italy;
| | - Rosario Rullo
- Department of Biomedical and Surgical and Biomedical Sciences Naples University, 80100 Naples, Italy;
| | - Michele Gaeta
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, 98100 Messina ME, Italy; (R.D.S.); (A.B.); (M.R.A.M.); (C.C.); (M.G.)
| | - Luca Fiorillo
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, School of Dentistry, University of Messina, 98100 Messina ME, Italy;
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Atzeni F, Gerardi MC, Masala IF, Alciati A, Batticciotto A, Sarzi-Puttini P. An update on emerging drugs for fibromyalgia treatment. Expert Opin Emerg Drugs 2017; 22:357-367. [PMID: 29250975 DOI: 10.1080/14728214.2017.1418323] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Fibromyalgia (FM) is a chronic disorder whose symptoms of pain, fatigue, sleep disturbances and depression have a devastating effect on patients' lives as it limits their ability to engage in everyday working and social activities, and make it difficult to maintain normal relationships with family, friends and employers. None of the currently available drugs are fully effective against the whole spectrum of symptoms. The aim of this narrative review is to summarise the data relating to the new therapeutic options that have become available over the last few years. Areas covered: Increasing efforts by the pharmaceutical industry have led to the introduction of new investigational drugs and new formulations of older drugs, and studies have been carried out in order to investigate the possibility of using drugs that are currently used for other diseases. Expert opinion: Slight improvements in the health of FM patients treated with drugs targeting a range of molecular mechanisms have been observed, but there is still no single drug that is capable of offering substantial efficacy against all of the characteristic symptoms of FM. The identification of new and improved therapies for FM requires consideration of the heterogeneity of the condition, which suggests the existence of different patient subgroups, a relationship between central and peripheral aspects of the pathophysiology, and the need for combined treatment with drugs targeting multiple molecular mechanisms.
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Affiliation(s)
- Fabiola Atzeni
- a Rheumatology Unit , University of Messina , Messina , Italy
| | | | | | - Alessandra Alciati
- d Department of Clinical Neurosciences , Villa San Benedetto Menni, Hermanas Hospitalarias, FoRiPsi , Como , Italy
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Lawson K. Emerging pharmacological strategies for the treatment of fibromyalgia. World J Pharmacol 2017; 6:1-10. [DOI: 10.5497/wjp.v6.i1.1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2016] [Revised: 01/06/2017] [Accepted: 02/13/2017] [Indexed: 02/06/2023] Open
Abstract
Fibromyalgia (FM) has been described as a chronic clinical condition related to multisensory hypersensitivity presenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a range of co-morbidities, such as fatigue, sleep disturbance, cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and noradrenaline levels within the central nervous system, e.g., tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, and voltage-gated calcium channel subunit ligands, e.g., gabapentin and pregabalin. Investigation of a range of novel targets, such as melatoninergic, cannabinoid, dopamine, NMDA, angiotensin, orexin and opioid receptors, and ion channels, in addition revisiting bioamine modulation and subunits has provided efficacy outcomes that improve the health status of patients with FM. Nevertheless, modest and limited efficacy is often observed reflecting the heterogeneity of FM with existence of subpopulations of patients, the contribution of peripheral and central components to the pathophysiology, and the extensive range of accompanying co-morbidities. The complexity and multidimensional nature of FM is emphasized by the diversity of pharmacological targets gaining interest. Clues to underlying mechanisms which offer themselves as novel and potential targets for new medications are being provided by advances in the understanding of the pathophysiology of FM.
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Aydın TH, Can ÖD, Demir Özkay Ü, Turan N. Effect of subacute agomelatine treatment on painful diabetic neuropathy: involvement of catecholaminergic mechanisms. Fundam Clin Pharmacol 2016; 30:549-567. [PMID: 27421789 DOI: 10.1111/fcp.12224] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 06/22/2016] [Accepted: 07/08/2016] [Indexed: 12/18/2022]
Abstract
In this study, we investigated the effects of subacute agomelatine (40 and 80 mg/kg) administration on chronic hyperglycemia, metabolic parameters, and pain perception in streptozotocin-induced diabetic rats. Fasting blood glucose measurements and oral glucose tolerance tests were performed to evaluate the effect of agomelatine on glycemia, while metabolic parameters were monitored using metabolic cages. Potential effect of agomelatine on diabetes-induced mechanical and thermal allodynia was evaluated using dynamic plantar aesthesiometer and warm plate (38 °C) tests, respectively. Additionally, influence of agomelatine on hyperalgesia occurring in connection with diabetic neuropathy was examined using the Randall-Selitto (mechanical nociceptive stimulus), Hargreaves (thermal nociceptive stimulus), and cold plate (4 °C, thermal nociceptive stimulus) tests. Obtained data indicated that, in diabetic rats, agomelatine significantly improved hyperalgesia and allodynia responses, without no effect on hyperglycemia or the associated polydipsia, polyuria, and hyperphagia. Therapeutic potential of agomelatine on neuropathic pain was suppressed with α-methyl-para-tyrosine methyl ester (an inhibitor of catecholamine synthesis), phentolamine (a nonselective α-adrenoceptor antagonist), and propranolol (a nonselective β-adrenoceptor antagonist) administrations. However, p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis) pretreatment could not be achieved to reverse these antihyperalgesic and antiallodynic effects. These results suggest that the curative effect of agomelatine on neuropathic pain is mediated through rising synaptic catecholamine levels as well as through interactions with both α- and β-adrenoceptors. To our knowledge, this is the first study to show findings that indicate catecholaminergic system mediated antihyperalgesic and antiallodynic effects of agomelatine.
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Affiliation(s)
- Taliha H Aydın
- Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey
| | - Özgür D Can
- Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey
| | - Ümide Demir Özkay
- Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey
| | - Nazlı Turan
- Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey
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Abstract
INTRODUCTION Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. AREAS COVERED A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. EXPERT OPINION Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.
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Affiliation(s)
- Kim Lawson
- a Department of Biosciences and Chemistry, Biomolecular Sciences Research Centre, Faculty of Health and Wellbeing , Sheffield Hallam University , Sheffield , UK
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Kasap M, Can ÖD. Opioid system mediated anti-nociceptive effect of agomelatine in mice. Life Sci 2016; 163:55-63. [PMID: 27590609 DOI: 10.1016/j.lfs.2016.08.031] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 08/18/2016] [Accepted: 08/29/2016] [Indexed: 11/16/2022]
Abstract
AIMS This study was planned to examine the antinociceptive efficacy of agomelatine against acute mechanical, thermal, and chemical nociceptive stimuli, as well as to determine the opioid receptor subtypes mediating these effects. MAIN METHODS Tail-clip, hot-plate, and acetic acid-induced writhing tests were performed to evaluate anti-nociceptive effect. Besides, possible effect of agomelatine on the motor coordination of animals was assessed with a Rota-rod test. KEY FINDINGS Agomelatine (40mg/kg and 60mg/kg) significantly prolonged the reaction time of mice in both the tail-clip and hot-plate tests, suggesting the antinociceptive activity is related to both spinal and supraspinal mechanisms. This drug also reduced the number of writhing behaviors indicating the presence of a peripherally mediated antinociceptive effect. Rota-rod testing displayed no notable effect on the motor activity of the animal supporting the conclusion that the observed antinociceptive effect is specific. The agomelatine-induced antinociceptive activity abrogated following pretreatment with naloxone (a non-selective opioid receptor antagonist, 5.48mg/kg, i.p.), which suggested the participation of opioid mechanisms to the antinociception. The possible contribution of μ, δ and ҡ subtypes of opioid receptors to the anti-nociceptive effect were evaluated using naloxonazine (7mg/kg, s.c.), naltrindole (0.99mg/kg, i.p.), and nor-binaltorphimine (1.03mg/kg, i.p.), respectively. Pretreatments using these antagonists abolished the antinociceptive activity of agomelatine in all of the nociceptive test paradigms used, which pointed out that μ, δ, and ҡ opioid receptors participated to the action of agomelatine on pain. SIGNIFICANCE These results demonstrated the therapeutic potential of agomelatine in the treatment of pain disorders.
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Affiliation(s)
- Merve Kasap
- Anadolu University Graduate School of Health Sciences, Department of Pharmacology, 26470 Eskişehir, Turkey
| | - Özgür Devrim Can
- Anadolu University, Faculty of Pharmacy, Department of Pharmacology, 26470 Eskişehir, Turkey.
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Agorastos A, Linthorst ACE. Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder. J Pineal Res 2016; 61:3-26. [PMID: 27061919 DOI: 10.1111/jpi.12330] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 04/05/2016] [Indexed: 12/21/2022]
Abstract
Loss of circadian rhythmicity fundamentally affects the neuroendocrine, immune, and autonomic system, similar to chronic stress and may play a central role in the development of stress-related disorders. Recent articles have focused on the role of sleep and circadian disruption in the pathophysiology of posttraumatic stress disorder (PTSD), suggesting that chronodisruption plays a causal role in PTSD development. Direct and indirect human and animal PTSD research suggests circadian system-linked neuroendocrine, immune, metabolic and autonomic dysregulation, linking circadian misalignment to PTSD pathophysiology. Recent experimental findings also support a specific role of the fundamental synchronizing pineal hormone melatonin in mechanisms of sleep, cognition and memory, metabolism, pain, neuroimmunomodulation, stress endocrinology and physiology, circadian gene expression, oxidative stress and epigenetics, all processes affected in PTSD. In the current paper, we review available literature underpinning a potentially beneficiary role of an add-on melatonergic treatment in PTSD pathophysiology and PTSD-related symptoms. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. We conclude that adjuvant melatonergic treatment could provide a potentially promising treatment strategy in the management of PTSD and especially PTSD-related syndromes and comorbidities. Rigorous preclinical and clinical studies are needed to validate this hypothesis.
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Affiliation(s)
- Agorastos Agorastos
- Department of Psychiatry and Psychotherapy, Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Astrid C E Linthorst
- Faculty of Health Sciences, Neurobiology of Stress and Behaviour Research Group, School of Clinical Sciences, University of Bristol, Bristol, UK
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Abstract
Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread pain and tenderness, accompanied by disturbed sleep, chronic fatigue and multiple additional functional symptoms. FMS continues to pose an unmet need regarding pharmacological treatment and many patients fail to achieve sufficient relief from existing treatments. As FMS is considered to be a condition in which pain amplification occurs within the CNS, therapeutic interventions, both pharmacological and otherwise, have revolved around attempts to influence pain processing in the CNS. In the current review, we present an update on novel targets in the search for effective treatment of FMS.
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Affiliation(s)
- Jacob N Ablin
- Institute of Rheumatology, Tel Aviv Sourasky Medical Center & Tel Aviv University Faculty of Medicine, Israel
| | - Winfried Häuser
- Department of Internal Medicine I, Klinikum Saarbrücken, 66119 Saarbrücken, Germany & Department of Psychosomatic Medicine & Psychotherapy, Technische Universität München, 81865 München, Germany
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Freiesleben SD, Furczyk K. A systematic review of agomelatine-induced liver injury. J Mol Psychiatry 2015; 3:4. [PMID: 25932327 PMCID: PMC4407422 DOI: 10.1186/s40303-015-0011-7] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Accepted: 04/11/2015] [Indexed: 02/06/2023] Open
Abstract
Agomelatine is an antidepressant with a unique mechanism of action. Since its marketing in 2009, concerns have been raised regarding its potential to induce liver injury. The authors therefore address the need to comprehensively evaluate the potential risk posed by agomelatine of inducing liver injury by reviewing data from published and unpublished clinical trials in both the pre- and postmarketing settings, as well as data from non-interventional studies, pharmacovigilance database reviews and one case report. Recommendations for clinicians are also provided. In this review, agomelatine was found to be associated with higher rates of liver injury than both placebo and the four active comparator antidepressants used in the clinical trials for agomelatine, with rates as high as 4.6% for agomelatine compared to 2.1% for placebo, 1.4% for escitalopram, 0.6% for paroxetine, 0.4% for fluoxetine, and 0% for sertraline. The review also provides evidence for the existence of a positive relationship between agomelatine dose and liver injury. Furthermore, rates of liver injury were found to be lower in non-interventional studies. Findings from pharmacovigilance database reviews and one case report also highlight the risk of agomelatine-induced liver injury. As agomelatine does pose a risk of liver injury, clinicians must carefully monitor liver function throughout treatment. However, agomelatine’s unique mechanism of action and favourable safety profile render it a valuable treatment option. A quantitative analysis of agomelatine-induced liver injury is lacking in the literature and would be welcomed.
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Affiliation(s)
- Silka Dawn Freiesleben
- Department of Psychiatry, University of Rostock, Gehlsheimerstraße 20, 18147 Rostock, Germany
| | - Karolina Furczyk
- Department of Psychiatry, University of Rostock, Gehlsheimerstraße 20, 18147 Rostock, Germany
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De Berardis D, Fornaro M, Serroni N, Campanella D, Rapini G, Olivieri L, Srinivasan V, Iasevoli F, Tomasetti C, De Bartolomeis A, Valchera A, Perna G, Mazza M, Di Nicola M, Martinotti G, Di Giannantonio M. Agomelatine beyond borders: current evidences of its efficacy in disorders other than major depression. Int J Mol Sci 2015; 16:1111-30. [PMID: 25569089 PMCID: PMC4307293 DOI: 10.3390/ijms16011111] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Accepted: 12/23/2014] [Indexed: 12/14/2022] Open
Abstract
Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. Agomelatine's antidepressant actions are attributed to its sleep-promoting and chronobiotic actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus, as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c receptors causes release of both noradrenaline and dopamine at the fronto-cortical dopaminergic and noradrenergic pathways. The combined actions of agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be effective in treating major depression. Moreover, evidence exists that points out a possible efficacy of such drug in the treatment of bipolar depression, anxiety disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative review was to elucidate current evidences on the role of agomelatine in disorders other than major depression.
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Affiliation(s)
- Domenico De Berardis
- National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy.
| | - Michele Fornaro
- Department of "Scienze della Formazione", University of Catania, 95121 Catania, Italy.
| | - Nicola Serroni
- Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy.
| | - Daniela Campanella
- Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy.
| | - Gabriella Rapini
- Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy.
| | - Luigi Olivieri
- National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy.
| | - Venkataramanujam Srinivasan
- Sri Sathya Sai Medical Educational and Research Foundation, Medical Sciences Research Study Center, Prasanthi Nilayam, 40-Kovai Thirunagar Coimbatore-641014, 641014 Tamilnadu, India
| | - Felice Iasevoli
- Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80131 Naples, Italy.
| | - Carmine Tomasetti
- Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80131 Naples, Italy.
| | - Andrea De Bartolomeis
- Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80131 Naples, Italy.
| | - Alessandro Valchera
- Hermanas Hospitalarias, FoRiPsi, Villa S. Giuseppe Hospital, 63100 Ascoli Piceno, Italy.
| | - Giampaolo Perna
- Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, 22032 Como, Italy.
| | - Monica Mazza
- National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy.
| | - Marco Di Nicola
- National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy.
| | - Giovanni Martinotti
- Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy.
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