Randomized controlled trials for fluoxetine in chronic pain management.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5210",leadTitle:null,fullTitle:"Fisheries and Aquaculture in the Modern World",title:"Fisheries and Aquaculture in the Modern World",subtitle:null,reviewType:"peer-reviewed",abstract:"This book has nine chapters on Aquaculture Wetland Ecosystem Services Approach and Climate Change Adaptation, which explain how different aquaculture systems could maximize the benefits that society receives from both aquaculture production and the ecosystem services provided by wetland ecosystems. Sustainable development of aquaculture must take into account the societal value of ecosystem services for an efficient and environmentally sound production of food. Although some issues regarding the potential benefits and implementation of sustainable aquaculture remain, the consideration of food security and minimizing ecosystem impacts suggest that the time has come to take action. If we can efficiently farm the land, why can’t we farm more the sea and inland waters?",isbn:"978-953-51-2687-4",printIsbn:"978-953-51-2686-7",pdfIsbn:"978-953-51-5453-2",doi:"10.5772/61558",price:119,priceEur:129,priceUsd:155,slug:"fisheries-and-aquaculture-in-the-modern-world",numberOfPages:214,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"1c78e2a5e686279a30ed3fb640769dad",bookSignature:"Heimo Mikkola",publishedDate:"September 28th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5210.jpg",numberOfDownloads:15296,numberOfWosCitations:32,numberOfCrossrefCitations:16,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:33,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:81,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 22nd 2015",dateEndSecondStepPublish:"November 12th 2015",dateEndThirdStepPublish:"February 8th 2016",dateEndFourthStepPublish:"March 9th 2016",dateEndFifthStepPublish:"April 8th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"144330",title:"Dr.",name:"Heimo",middleName:"Juhani",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola",profilePictureURL:"https://mts.intechopen.com/storage/users/144330/images/system/144330.png",biography:"Heimo Mikkola obtained a Ph.D. from the University of Kuopio (now Eastern Finland University), where he also served as an adjunct professor in Applied Zoology. From 1974 to 2007, he worked with the Food and Agriculture Organization (FAO) of the United Nations, first in Colombia and then in Africa, where he served as the organization’s resident representative. After retiring from the FAO in Uruguay, Dr. Mikkola has worked as a part-time professor at three Kazakh universities and one Kyrgyz university. His work has taken him to 137 countries, and he has written almost 700 reports and scientific papers and books, mainly on owls and other birds, fish, insects, and food. He has studied bats for many years on almost all continents as they often share night-time activity and biotopes with owls. This is the second book on bats he has edited for IntechOpen.",institutionString:"University of Eastern Finland",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"10",totalChapterViews:"0",totalEditedBooks:"9",institution:{name:"University of Eastern Finland",institutionURL:null,country:{name:"Finland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"348",title:"Ichthyology",slug:"agricultural-and-biological-sciences-marine-biology-ichthyology"}],chapters:[{id:"50289",title:"Effect of Special Fish Feed Prepared Using Food Industrial Waste on Labeo rohita",doi:"10.5772/62736",slug:"effect-of-special-fish-feed-prepared-using-food-industrial-waste-on-labeo-rohita",totalDownloads:2276,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"All food processing industries generate wastes of varying nature in significant quantities. Managing these wastes so as to minimize the impact on the environment is the prime concern. The concept of waste has undergone much change in recent times, with the focus being on utilizing the waste materials as inputs for generation of new or reusable products. Vegetable and fruit wastes are generated in significant quantities and are easily available at minimal charge. The comparative utilization of these wastes as a dietary ingredient was assessed employing the Labeo rohita fingerlings as the test species. The study was conducted over a period of 60 days. Orange peels and potato peels are characterized, and then, formulation of orange peel feed (OPF) and potato peel feed (PPF) was carried out. Market common fish feed (CFF) was taken as a control. The three test diets were designated as CFF, OPF and PPF. Feeding was done once daily. The water quality parameters such as dissolved oxygen, water temperature pH, total alkalinity, total hardness; calcium hardness and magnesium hardness as well as growth response were monitored at fortnightly intervals. The quality of water was maintained by periodic partial replenishment over the period of study. On termination of the trial, higher growth response was recorded in the PPF treatment. The initial and final weight and length of fishes was recorded. The results shows significant growth in PPF and OPF showed brighter body scales than other two feed. Fishes were very healthy and normal throughout the study period indicating no adverse effect on their health. No infection whatsoever was noted during 60 days of experimental period.",signatures:"Sanyogita R. Verma and Shanta Satyanarayan",downloadPdfUrl:"/chapter/pdf-download/50289",previewPdfUrl:"/chapter/pdf-preview/50289",authors:[{id:"183699",title:"Dr.",name:"Verma",surname:"Sanyogita",slug:"verma-sanyogita",fullName:"Verma Sanyogita"},{id:"185353",title:"Dr.",name:"Shanta",surname:"Satyanarayan",slug:"shanta-satyanarayan",fullName:"Shanta Satyanarayan"}],corrections:null},{id:"50402",title:"Using Taxes to Manage a Multigear Fishery: An Application to a Spanish Fishery",doi:"10.5772/62285",slug:"using-taxes-to-manage-a-multigear-fishery-an-application-to-a-spanish-fishery",totalDownloads:1402,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"When fishing gears alter the composition of fish populations or modify the recruitment rate, it is advisable to include the degree of their fishing selectivity in the analysis. Fishing selectivity can cause two different management problems: interspecies selectivity or by‐catch of fish stocks for which no quota has been set by the regulator. The case study is the Spanish fishery of hake (Merlucius merlucius), where the fleet operates using two main gears; most of the vessels are trawlers but a few boats use longlines and other fixed gears. Fishery management by means of effort taxes and how the degree of intraspecies selectivity may affect the resource and tax levels are analyzed. The results show that the tax level will depend on the social value of the marine stock, the marginal productivity of each fleet's effort, and the effect that the fishing activity of each one has on the growth of the hake biomass.",signatures:"M. Dolores Garza‐Gil, Manuel Varela‐Lafuente and Juan C. Surís‐\nRegueiro",downloadPdfUrl:"/chapter/pdf-download/50402",previewPdfUrl:"/chapter/pdf-preview/50402",authors:[{id:"54866",title:"Prof.",name:"M. Dolores",surname:"Garza-Gil",slug:"m.-dolores-garza-gil",fullName:"M. Dolores Garza-Gil"},{id:"59592",title:"Prof.",name:"Manuel M.",surname:"Varela-Lafuente",slug:"manuel-m.-varela-lafuente",fullName:"Manuel M. Varela-Lafuente"},{id:"180732",title:"Prof.",name:"Juan C.",surname:"Surís-Regueiro",slug:"juan-c.-suris-regueiro",fullName:"Juan C. Surís-Regueiro"}],corrections:null},{id:"52369",title:"Pan-Arctic Fisheries and their Assessment",doi:"10.5772/64745",slug:"pan-arctic-fisheries-and-their-assessment",totalDownloads:1500,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Pan-Arctic fisheries are highly diverse in their purpose, species biology, productivity, economic and strategic importance as well as in how they are prosecuted. They range from full industrial fisheries to community-based artisanal, sport and subsistence fisheries. The nature of Arctic ecosystems in the region varies from extremely productive to relatively barren in terms of fisheries production. Gear types vary, but offshore trawl fisheries and inshore and freshwater gillnet fisheries are the most common. Rights-based fisheries (e.g., for indigenous inhabitants) are more prominent in the Canadian and American Arctic than in European jurisdictions. The principal harvested species in freshwater environments tend to be from few taxa mainly Salvelinus spp. and from the family Coregonidae, while the marine taxa are more diverse. Compared to north temperate fisheries, Arctic fisheries have impressive variation across longitudes; some jurisdictions support only small-scale subsistence fisheries, whereas others contain some of the largest yields among industrial fisheries. Approaches to scientific assessment are also highly diverse with a range from catch-based indicators to sophisticated fully age-structured population models.",signatures:"Ross Tallman, Muhammed Y. Janjua, Daniel Howell, Burton Ayles,\nTheresa Carmicheal, Matthias Bernreuther, Steve Ferguson and\nMargaret Treble",downloadPdfUrl:"/chapter/pdf-download/52369",previewPdfUrl:"/chapter/pdf-preview/52369",authors:[{id:"181128",title:"Dr.",name:"Ross",surname:"Tallman",slug:"ross-tallman",fullName:"Ross Tallman"}],corrections:null},{id:"50583",title:"Trawl Selectivity in the Barents Sea Demersal Fishery",doi:"10.5772/63019",slug:"trawl-selectivity-in-the-barents-sea-demersal-fishery",totalDownloads:1694,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter provides a general overview of the Barents Sea demersal trawl fishery. First, it reviews historical catch levels and current biomass status of four commercially important demersal species (cod, haddock, Greenland halibut, and redfish) and includes an overview of their management plan that has been carried out by the Joint Norwegian–Russian commission. Then, it presents the evolution of the technical regulations for improving size selectivity in this fishery and describes current challenges in gear selectivity. Later, this chapter describes the concept of size selectivity, introduces the selective parameters that define a selection curve, and progressively introduces different parametric models that describe the selection process. The most common experimental methods and gear used to collect selectivity data are described, and their advantages and disadvantages are discussed. Finally, this chapter describes an alternative, or a complementary method, to the conventional estimation of trawl selectivity—the FISHSELECT method. This method is based on morphology measurements and fish penetration models to estimate the selective properties of different mesh shapes and sizes at different mesh openings, which are later used to provide simulation-based prediction of size selectivity. FISHSELECT has already been applied to four important species of the Barents Sea Demersal Fishery, and the results have in all cases showed to be coherent with the results obtained from sea trial results.",signatures:"Eduardo Grimaldo, Manu Sistiaga, Bent Herrmann and Roger B.\nLarsen",downloadPdfUrl:"/chapter/pdf-download/50583",previewPdfUrl:"/chapter/pdf-preview/50583",authors:[{id:"107079",title:"Dr.",name:"Eduardo",surname:"Grimaldo",slug:"eduardo-grimaldo",fullName:"Eduardo Grimaldo"},{id:"185311",title:"Dr.",name:"Manu",surname:"Sistiaga",slug:"manu-sistiaga",fullName:"Manu Sistiaga"},{id:"185312",title:"Dr.",name:"Bent",surname:"Herrmann",slug:"bent-herrmann",fullName:"Bent Herrmann"},{id:"185313",title:"Prof.",name:"Roger B.",surname:"Larsen",slug:"roger-b.-larsen",fullName:"Roger B. Larsen"}],corrections:null},{id:"50559",title:"Oil and Gas Platforms in the Gulf of Mexico: Their Relationship to Fish and Fisheries",doi:"10.5772/63026",slug:"oil-and-gas-platforms-in-the-gulf-of-mexico-their-relationship-to-fish-and-fisheries",totalDownloads:1639,totalCrossrefCites:7,totalDimensionsCites:15,hasAltmetrics:0,abstract:"There are over 2300 standing oil and gas platforms in the northern Gulf of Mexico (GOM). It has been argued that platforms provide reef-like habitat that increases the growth and survival rates of fishes by increasing prey availability and affording shelter for protection from predators, provide additional spawning substrate, and by acting as a visual attractant for organisms not otherwise dependent upon hard bottom. Platforms differ from most natural habitats, and from traditional artificial reefs, in that their vertical profile extends upward through the water column into the photic zone and the sea surface. Increased habitat quality on, or immediately around, oil and gas platforms are thought to be derived from increased in situ food production associated with encrustation by fouling organisms. In this chapter, we address the issue of how to evaluate the role of artificial reefs by first establishing levels of evaluation for individual fish species found on oil and gas platforms in the GOM. The levels of evaluation relate to the amount and adequacy of the available information, which was populated with an extensive literature and data search. Three levels of assessment are established, analogous to the levels of analysis established National Oceanographic and Atmospheric Administration (NOAA) Fisheries for identification of Essential Fish Habitat. More than 1300 documents, including reports, stock assessments, other gray literature, and papers published in the primary literature, were used to complete this chapter. When available, published literature was the preferred source of information.",signatures:"James H. Cowan and Kenneth A. Rose",downloadPdfUrl:"/chapter/pdf-download/50559",previewPdfUrl:"/chapter/pdf-preview/50559",authors:[{id:"139993",title:"Dr.",name:"James",surname:"Cowan, Jr.",slug:"james-cowan-jr.",fullName:"James Cowan, Jr."}],corrections:null},{id:"50363",title:"The Brown Seaweeds Fishery in Chile",doi:"10.5772/62876",slug:"the-brown-seaweeds-fishery-in-chile",totalDownloads:1733,totalCrossrefCites:4,totalDimensionsCites:10,hasAltmetrics:0,abstract:"Chilean fishery of brown algae includes species belonging to the genus Lessonia, Durvillaea, and Macrocystis, which can be found along the coast, ranging latitudes from 18° to 55°S. The exploitation of these seaweeds is done mainly in the Northern coast because the environmental conditions of this region decrease initial production costs. Brown algae are exploited from natural populations and exported to international markets as row material, source of alginates, widely utilized in diverse manufacturing processes and industries. International demand for Chilean kelps has produced sustained increase in harvest during the last decade, reaching more than 390,000 dry tons/year. This chapter approaches the most relevant aspects of the brown seaweed fishery in Chile which covers a wide range of the Southeast Pacific coast, considering the number of commercial species, its abundance and distribution, knowledge achieved on their ecology and biology regarding management, and conservation of these resources, and finally, provides tools for stakeholders and policy makers directed to sustainable management of natural kelp beds occurring in the cold temperate seas.",signatures:"Julio A. Vásquez",downloadPdfUrl:"/chapter/pdf-download/50363",previewPdfUrl:"/chapter/pdf-preview/50363",authors:[{id:"180745",title:"Dr.",name:"Julio",surname:"Vásquez",slug:"julio-vasquez",fullName:"Julio Vásquez"}],corrections:null},{id:"52331",title:"Setting Up Traceability Tools for the Indonesian Blue Swimming Crab Fishery: A Case Study in Southeast Sulawesi",doi:"10.5772/64252",slug:"setting-up-traceability-tools-for-the-indonesian-blue-swimming-crab-fishery-a-case-study-in-southeas",totalDownloads:1678,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"The Indonesian blue swimming crab fishery developed rapidly during the 1990s to become an important source of income for coastal communities. The blue swimming crab (BSC) in 2015 is the third highest export commodity in Indonesia, primarily to USA markets. Southeast (SE) Sulawesi is a relatively minor area for blue swimming crab production (approximately 1200–2000 mt per annum), in which only a subset of Asosiasi Pengelolaan Rajungan Indonesia (APRI) members are active, and it may be a conducive region in which to conduct a pilot activity to form a fisheries management structure that demonstrates the benefits that can be achieved via collaboration. The control document (CD) is a traceability and documentation process to be implemented by all of the segments of the supply chain (collectors/cooking stations, miniplants, and processors) in order to promote compliance to new Ministry and Marine Affair (MMAF) regulations and generate the records and documents of the supply chain application and verification of the new regulations. The self-recorded logbook by the fishermen and miniplant, as the point in the supply chain, could help with a meaningful and long-term solution to the fishery management in Southeast Sulawesi. This is the first trial of CD in Indonesia and could be a good model for BSC fishery in other region in Indonesia.",signatures:"Hawis Madduppa, Zairion, Siti Nuraini, Kuncoro Nugroho and\nBambang Arif Nugraha",downloadPdfUrl:"/chapter/pdf-download/52331",previewPdfUrl:"/chapter/pdf-preview/52331",authors:[{id:"180161",title:"Dr.",name:"Hawis",surname:"Madduppa",slug:"hawis-madduppa",fullName:"Hawis Madduppa"},{id:"185944",title:"Dr.",name:"Zairion",surname:"Zairion",slug:"zairion-zairion",fullName:"Zairion Zairion"},{id:"185945",title:"Mrs.",name:"Siti",surname:"Nuraini",slug:"siti-nuraini",fullName:"Siti Nuraini"},{id:"185946",title:"Mr.",name:"Bambang Arif",surname:"Nugraha",slug:"bambang-arif-nugraha",fullName:"Bambang Arif Nugraha"},{id:"185947",title:"Mr.",name:"Kuncoro Catur",surname:"Nugroho",slug:"kuncoro-catur-nugroho",fullName:"Kuncoro Catur Nugroho"}],corrections:null},{id:"50462",title:"Direction of Fisheries (SUISAN) Education from a Historical Perspective in Japan",doi:"10.5772/62733",slug:"direction-of-fisheries-suisan-education-from-a-historical-perspective-in-japan",totalDownloads:1425,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Fishing, aquaculture, and food processing is collectively referred to as “SUISAN”, and the term was translated to “fisheries” in the Meiji period. Fisheries education in Japan was at its dawn. Fisheries education was necessary for improvement of local fisheries subsistence. Fisheries education was performed, centering on nurturing of mid-career engineers for deep-sea fishing after 1950s. However, when the Heisei period in the 1990s started, “participatory = citizen involvement type fisheries education” was promoted extensively. Future establishment of a Japanese version of Sea Grants is desired to promote citizen involvement in fisheries education with systematized involvement of universities, research institutions, aquaria, and local people.",signatures:"Tsuyoshi Sasaki",downloadPdfUrl:"/chapter/pdf-download/50462",previewPdfUrl:"/chapter/pdf-preview/50462",authors:[{id:"180712",title:"Dr.",name:"Tsuyoshi",surname:"Sasaki",slug:"tsuyoshi-sasaki",fullName:"Tsuyoshi Sasaki"}],corrections:null},{id:"51124",title:"Fishery Status and Taxonomy of the Carangids (Pisces) in the Northern Arabian Sea Coast of Pakistan",doi:"10.5772/62627",slug:"fishery-status-and-taxonomy-of-the-carangids-pisces-in-the-northern-arabian-sea-coast-of-pakistan",totalDownloads:1952,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The objectives of this study were i) to evaluate number of existing members of the family Carangidae in the area ii) to establish a distinguishable and lucid key based on the taxonomic characteristics, meristic count and otolith description. In this study, thirty-six species were collected from the main fish landing facilities between 2012~2015. Fish body colour, taxonomic characteristics, fin rays and otolith shape description were used to identify each species. Otolith description comprises of shape of ostium, sulcus and margins of anterior and posterior surface along with distinct definite shape possess by each species make it easier for identification.",signatures:"Nazia Qamar, Sher Khan Panhwar and Ghazala Siddiqui",downloadPdfUrl:"/chapter/pdf-download/51124",previewPdfUrl:"/chapter/pdf-preview/51124",authors:[{id:"182414",title:"Dr.",name:"Sher Khan",surname:"Panhwar",slug:"sher-khan-panhwar",fullName:"Sher Khan Panhwar"},{id:"184264",title:"Dr.",name:"Nazia",surname:"Qamar",slug:"nazia-qamar",fullName:"Nazia Qamar"},{id:"184265",title:"Prof.",name:"Ghazala",surname:"Siddiqui",slug:"ghazala-siddiqui",fullName:"Ghazala Siddiqui"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5705",title:"Future Foods",subtitle:null,isOpenForSubmission:!1,hash:"3e0407db8b07ae39128d6454b67bc690",slug:"future-foods",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/5705.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6478",title:"Bats",subtitle:null,isOpenForSubmission:!1,hash:"90a4ab5d70985630b12f49cb23939c02",slug:"bats",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/6478.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited 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The target is, hopefully, to achieve “net-zero” greenhouse gas by 2050 and switch to clean power to fuel much of the transportation, buildings and industry. Therefore, intensive research and collaborative projects dealing with the installation of many wind turbines, both onshore and offshore, have taken place to decarbonize electricity grid systems through the exploitation of wind power. In this context, modern and larger horizontal-axis wind turbines with power capacity reaching 15 MW and rotors of more than 230-meter diameter are under continuous development for the merit of minimizing the unit cost of energy production. Such valuable advances in this competitive source of clean energy have made vast research contributions in developing wind industry technologies worldwide.
\r\n\r\n\tIn addition to the confrontation with the social acceptance, transport and erection, and sustainability of political and economic support for wind energy exploitation, the main challenges for a continued up-sizing of wind turbines in the future are the accurate wind measurements, materials and structures of the rotating blades which are expected to be fully made of carbon fibers, development of drive train technologies using permanent magnet generators, as well as multi-stage gearboxes, which could improve reliability. Towers will continue to be made of steel and/or concrete in the form a modular construction.
\r\n\r\n\tThis book aims to present advances and challenges of the design, manufacture and operation of wind turbines, and to provide a rich platform of research to the field of wind turbines. Suggested topics encompass wind measurement and forecasting, rotor blades, drive train technology, construction of tower and foundation, system integration and diagnostics, as well as offshore wind industry. The authors are encouraged to combine design, manufacturing processes and operation and maintenance procedures with a description of the implemented approaches and techniques, dealing with the individual subject as they find appropriate.
",isbn:"978-1-80355-493-8",printIsbn:"978-1-80355-492-1",pdfIsbn:"978-1-80355-494-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"bb4190017e28a8332ce6b3e791ddeef1",bookSignature:"Prof. Karam Youssef Maalawi",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11176.jpg",keywords:"Wind, Wind Turbine, Wind Measurement, Rotor Blade, Drive Train, Tower, System Integration, Offshore Wind Industry, Weather Model, Erection Procedure, Floating Foundation, Storage Technology",numberOfDownloads:184,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 15th 2021",dateEndSecondStepPublish:"November 24th 2021",dateEndThirdStepPublish:"January 23rd 2022",dateEndFourthStepPublish:"April 13th 2022",dateEndFifthStepPublish:"June 12th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"7 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Prof. Karam Youssef Maalawi is a holder of two distinguished awards in Engineering science and the Albert Nelson Marquis Lifetime Achievement Award. He is also a consultant engineer at the Egyptian Organization for Standards and Quality and the rapporteur of the Technical Committee for Energy Systems Management. He was endorsed by Marquis Who's Who as a leader in the aerospace engineering industry.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"18593",title:"Prof.",name:"Karam",middleName:"Youssef",surname:"Maalawi",slug:"karam-maalawi",fullName:"Karam Maalawi",profilePictureURL:"https://mts.intechopen.com/storage/users/18593/images/system/18593.jpeg",biography:"Karam Y. Maalawi is a professor of Aeronautics and Mechanics at the Mechanical Engineering Department, National Research Centre in Cairo, Egypt. He holds a Bachelor of Science, Master of Science, and Doctor of Philosophy degrees in Aerospace Engineering (Cairo University). 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"63750",title:"Serotonin Reuptake Inhibitors and Their Role in Chronic Pain Management",doi:"10.5772/intechopen.80711",slug:"serotonin-reuptake-inhibitors-and-their-role-in-chronic-pain-management",body:'\nChronic pain is recognized today as a disease [1], affects almost 20% of the population [2], and represents a significant cause of disability bringing along high secondary social costs. The management of chronic pain involves pharmacological and interventional tools and become a priority for healthcare systems. This chapter aims to summarize the role of serotonin reuptake inhibitors (SRI) in the treatment of chronic pain. SRI includes selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI).
\nDefined as the pain that lasts more than 3 months, frequent after the disappearance of the causal factor, chronic pain shows numerous risk factors (socio-demographic, biological, clinical, and psychological). Thus, most affected are females, older people, and people with low socio-economic level. A significant risk for developing chronic pain is the pain itself (acute and chronic at other sites), and also are incriminated the geographical background, occupational factors, and the history of abuse and violence. Neuroimaging studies have already proved the changes in the brain with severe pain, reversible with proper treatment, and also suggested its importance for preventing the chronicization of pain [3]. The treatment of chronic pain is multi/interdisciplinary and multimodal, targeting different mechanisms of pain. We summarized some critical pain syndromes, which benefit from the SRI medication.
\nDiabetes mellitus affects billions of people worldwide. The painful diabetic neuropathy (PDPN) occurs in 20% of diabetes patients during the disease. Risk factors include age, hypertension, obesity, alcohol abuse, and smoking.
\nPathogenesis implies endoneurial microangiopathy and axonal loss, especially in sensory nerves. Aldose reductase activation by increasing polyol flux and the deposition of advanced glycated end-products are the primary determinants of PDPN. Secondary ischemia leads to enhanced oxidative stress and high production of free radicals, which leads to nerve damage [4].
\nClinical PDPN may present as burning, stabbing, dull and aching, or sharp pain. In some instances, allodynia (painful response to a normally non-noxious stimulus) might accompany pain. PDPN is symptomatic mainly in the lower limbs and progresses proximally. Patients with PDPN show skin changes and loss of sensory that could lead further to diabetic ulcers.
\nThe medication of painful diabetic neuropathy includes duloxetine, venlafaxine, tricyclic antidepressants (TAD), oxcarbazepine, and tapentadol. Overall, the quality of life in patients with PDPN is poor [5].
\nFibromyalgia (FM) is a syndrome composed of widespread chronic pain, muscle fatigue, and functional symptoms. It shows a genetic predisposition, but environmental factors play a prominent place during the disease. FM pathogenesis involves modified inflammatory response and oxidative stress [6].
\nDiagnosis is difficult because of the variety of clinical symptoms—75% of these patients do not meet the inclusion criteria, thus often they lack the diagnosis. Besides, these patients develop sleep disturbances and sexual dysfunction, altering further the quality of life.
\nThe current evidence suggest for FM management antidepressants, cardiovascular exercise, and cognitive behavioral therapy [7]. Meta-analysis results agree that the medication approved by FDA—milnacipran—and duloxetine are effective in FM while there are concerns that the results showed only a moderate effect on pain and sleep, and no impact on fatigue [8].
\nTension-type headache (TTH) is a typical headache (up to 78%), caused by the contractions of muscles of the scalp, neck, and jaw, and triggered mainly by stress and emotional conflicts. It is described as a moderate pressure applied to the frontal area, around the head or neck, and according to its frequency is classified as infrequent, frequent, and chronic.
\nChronic TTH results as a consequence of sensitization of the pain pathway due to persistent pericranial myofascial nociceptive input. This TTH shows a frequency of at least 15 days/month for at least 3 months. If nausea and vomiting are present, exclude the diagnosis of TTH. Photophobia may occur in TTH.
\nTreatment of the acute episodes of TTH includes nonsteroidal anti-inflammatory drugs and acetaminophen, while their prevention associates pharmacologic and non-pharmacologic (physical and psychologic therapy) interventions. Tricyclic antidepressants (amitriptyline) are the most studied drugs in TTH, but new studies showed efficacy for other antidepressants including SRI—citalopram, sertraline, venlafaxine, and paroxetine [9].
\nSomatoform pain (SP) is the primary symptom in an ambiguous and unclarified category called somatization spectrum disorders (SSD), defined as the displaying of somatic complaints as a result of social stress. It shows a growing incidence (up to 60%) and is a symptom generally unexplained by the medical condition of these patients (which must be ruled out). The symptomatology—headache and musculoskeletal pain—overlaps with other chronic pain syndromes and may be associated with psychiatric symptoms (depression, anxiety, personality disorders) and thus makes the diagnosis difficult. The mechanism of this condition is a subject of debate, but a genetic predisposition plus an altered interpersonal relationship in childhood and adolescence are the determining factors [10].
\nTreatment is focused on psychotherapy and modulation of interpersonal relations, by learning to develop robust, safe, and supportive social relationships. Besides, acupuncture and massage proved efficacy. Medication includes TADs and SSRIs [11].
\nDue to the association between chronic pain states and depression and also due to the continuous need and search for effective analgesic drugs, antidepressants have long been considered for the treatment of chronic pain. Some antidepressants are useful in the management of pain syndromes showing analgesic effects, but not all antidepressants have analgesic properties [12]. TADs are recognized to have analgesic effects in doses lower than the antidepressant ones. However, frequent side effects preclude their widespread use.
\nConsequently, newer generations of antidepressants, like SSRIs and SNRIs, have been studied in chronic pain management. For SSRIs, efficiency in chronic pain conditions has been debated, and results are still inconclusive. It is felt that antidepressants with both noradrenergic and serotoninergic activities are superior analgesics compared to drugs that possess only serotoninergic activity [13].
\nCurrently available SSRIs are fluoxetine, sertraline, paroxetine, citalopram, and escitalopram. Fluvoxamine is approved for the treatment of obsessive-compulsive disorders but has sometimes been used off-label for the treatment of depression. SSRIs are currently approved and used for the treatment of a wide range of diseases: depression, anxiety and panic disorders, obsessive-compulsive disorders, post-traumatic stress disorder, premenstrual dysphoric syndrome, dysthymia, irritable bowel syndrome, eating disorders, alcohol abuse, and some personality disorders [14].
\nSSRIs utility for the treatment of chronic pain has been questioned but seems attractive due to their better side-effect profile compared to first-generation antidepressants like TADs, as SSRIs selectively block serotonin reuptake (reabsorption in the synaptic cleft).
\nEven though widely prescribed, the mechanism of action of SSRIs is not yet fully understood. The traditional theories claim the fact that antidepressant drugs act by influencing certain brain neurotransmitters [15]. Serotonin (5-HT) is one of the neurotransmitters which carry signals between neurons. The monoamine signaling theory of depression explains how SSRIs and other antidepressants work at the synaptic level by inhibiting the reuptake of one or several neurotransmitters, an effect which is almost immediate and leads to the increase of the extracellular level of the mediator. SSRIs are selective inhibitors of the presynaptic 5-HT reuptake transporter (SERT) that leads to an acute increase in serotonin concentrations in the synaptic cleft. This effect does not explain why antidepressant drugs work 2–4 weeks after treatment commencement, which might be better explained by receptor downregulation and delayed desensitization of presynaptic serotonin receptors [16]. Recent findings also suggest changes in brain-derived neurotrophic factor expression, which might even lead to SSRI antidepressant effect. Another newer theory suggests that SSRIs impact brain levels of allopregnanolone, enhancing gamma-amino butyric functions in the brain [14]. Apart from monoamine neurotransmitter’s imbalance, the inflammatory theory of depression claims the increased serum levels of proinflammatory mediators in the depressed patients [17]. As inflammation is the well-known cause of acute and some type of chronic pain, proinflammatory mediators play the capital role in initiating nociception and peripheral sensitization.
Possible side effects observed during antidepressant treatment with SSRIs also need to be considered when prescribing SSRIs for chronic pain management.
\nThese side effects include [12, 14, 24]:
Drowsiness, dry mouth, blurred vision, dizziness
Gastrointestinal effects: nausea, diarrhea or constipation, vomiting
Central nervous system effects: insomnia, agitation or restlessness, headache, tremors, increased sweating, rarely extrapyramidal symptoms, anorexia
Syndrome of inappropriate antidiuretic hormone secretion with hyponatremia, somnolence, delirium, confusion
Sexual dysfunction
Weight gain
Platelet dysfunction and increased risk of bleeding
Drug interactions due to the concomitant hepatic metabolism involving the cytochrome P450
Safety issues in pregnancy
Serotonin syndrome
Suicide might be a risk occurring early in the treatment, even though larger epidemiological studies do not confirm this assumption [14].
\nSSRIs discontinuation syndrome is characterized by sensory and gastrointestinal symptoms, dizziness, lethargy, and sleep disturbances [25].
\nFluoxetine (Prozac™, Sarafem™) has been one of the first SSRIs available for the treatment of depression. Its use for chronic pain management has been highlighted in several clinical trials including modest numbers of patients (Table 1). For chronic tension-type headache, fluoxetine administered in 20 mg daily dose is equally efficient to desipramine [26]. For the treatment of painful diabetic neuropathy, fluoxetine is no more effective than placebo and ameliorates pain in 48% of the patients, especially the depressed ones [27]. For somatoform pain disorders, the analgesic effect is related to treatment duration and is related to its antidepressant effect as depressive patients show greater improvement compared to non-depressed ones [28]. Fluoxetine was found to be efficient for the treatment of fibromyalgia when compared to placebo or amitriptyline [29, 30].
\n\n | Study | \nChronic pain condition | \nDose used for chronic pain (mg) | \nNo patients | \nComparator | \nEfficiency | \n
---|---|---|---|---|---|---|
Fluoxetine 10–80 mg/day for depression [14] | \nWalker et al. [26] | \nChronic tension-type headache | \n20 | \n25 | \nDesipramine | \nEqually efficient | \n
Max et al. [27] | \nDiabetic neuropathy | \n40 | \n46 | \nPlacebo | \nEqually efficient | \n|
Luo et al. [28] | \nSomatoform pain disorders | \n20 | \n80 | \nPlacebo | \nEfficient for depressed patients | \n|
Goldenberg et al. [29] | \nFibromyalgia | \n20 | \n19 | \nAmitriptyline | \nEffective | \n|
Arnold et al. [30] | \nFibromyalgia | \n45 ± 25 | \n60 | \nPlacebo | \nEffective | \n
Randomized controlled trials for fluoxetine in chronic pain management.
Fluvoxamine (Luvox™) is currently used for the treatment of obsessive-compulsive disorders, and the therapeutic dose varies widely between 50 and 300 mg. Non-depressed patients with severe chronic tension-type headache respond to fluvoxamine 50–100 mg daily [31], and it is efficient in central post-stroke pain, cancer pain, and osteoarthritis [32, 33, 34]. However, for chronic cancer pain, its beneficial effect has not yet been proven [35].
\nSertraline (Zoloft™) is recommended in single daily doses of 50–200 mg for the treatment of depression. In small sample size studies, it has proven to be efficient in non-cardiac chronic chest pain and chronic pelvic pain of prostatic origin in men [36, 37], but not in women with chronic pelvic pain [38].
\nParoxetine (Paxil™, Seroxat™) is one of the most extensively studied SSRI for chronic pain management (Table 2). For tension-type daily headache, two studies failed to prove any beneficial effect [39, 40]. Foster et al. suggested that by extending treatment periods up to 3–9 months, patients may benefit [41]. For chronic low back pain, doses of 20 mg are less efficient than maprotiline, and the effects are similar to placebo [42, 43]. In fibromyalgia, paroxetine improves overall symptomatology, but the effect on pain is less robust [44]. Paroxetine has been shown to be useful for the treatment of diabetic peripheral neuropathy, but not more efficient than imipramine [45]. In a mixed study comparing paroxetine and citalopram versus gabapentin, the comparable efficiency of these two SSRIs with gabapentin was shown [46].
\n\n | Study | \nChronic pain condition | \nDose used for chronic pain (mg) | \nNo of patients | \nComparator | \nEfficiency | \n
---|---|---|---|---|---|---|
Paroxetine 10–50 mg daily for depression [14] | \nLangemark and Olesen [39] | \nChronic tension-type headache | \n20–30 | \n50 | \nSulpiride | \nLess efficient | \n
Holroyd et al. [40] | \nChronic headache, non-responding to amitriptyline | \nUp to 40 | \n31 | \nPlacebo | \nModest effect | \n|
Foster and Bafaloukos [41] | \nChronic daily headache | \n10–50 | \n48 | \nPlacebo | \nEfficient when used for 3–9 months | \n|
Dickens et al. [42] | \nChronic low back pain | \n20 | \n91 | \nPlacebo | \nNot efficient | \n|
Atkinson et al. [43] | \nChronic low back pain | \n20 | \n74 | \nMaprotiline | \nLess efficient | \n|
Patkar et al. [44] | \nFibromyalgia | \n12.5–2.5 mg | \n116 | \nPlacebo | \nInconclusive | \n|
Sindrup et al. [45] | \nDiabetic peripheral neuropathy | \n40 | \n29 | \nPlacebo and imipramine | \nEfficient compared to placebo, less efficient compared to imipramine | \n|
Giannopoulos et al. [52] | \nDiabetic peripheral neuropathy | \n20–40 | \n101 | \nCitalopram or paroxetine | \nComparable efficiency | \n
Randomized controlled trials for paroxetine in chronic pain management.
Citalopram (Celexa™, Cipramil™) is administered in 10–80 mg dose once daily for the treatment of depression (Table 3). It has been investigated for the treatment of fibromyalgia and chronic tension-type headache, with no beneficial results [47, 48, 49], while for somatoform pain disorders it has only moderate analgesic effect [50, 51, 52].
\n\n | Study | \nChronic pain condition | \nDose used for chronic pain (mg) | \nNo of patients | \nComparator | \nEfficiency | \n|
---|---|---|---|---|---|---|---|
Citalopram 10–80 mg for depression [14] | \nNørregaard et al. [46] | \nFibromyalgia | \n20–40 | \n43 | \nPlacebo | \nNo effect | \n|
Anderberg et al. [47] | \nFibromyalgia | \n20–40 | \n40 | \nPlacebo | \nInconclusive | \n||
Aragona et al. [48] | \nSomatoform pain disorder | \n20 | \n35 | \nReboxetine | \nModerate effect | \n||
Bendsten et al. [49] | \nChronic tension-type headache | \n20 | \n40 | \nPlacebo and amitriptyline | \nNo significant effect | \n||
Viazis et al. [50] | \nGastroesophageal reflux disease | \n20 | \n63 | \nEfficient when administered with proton pump inhibitors | \n|||
Roohafza et al. [51] | \nPediatric functional abdominal pain | \n20 | \n86 | \nPlacebo | \nEffective | \n||
Giannopoulos et al. [52] | \nDiabetic peripheral neuropathy | \n20–40 | \n101 | \nCitalopram or paroxetine | \nComparable efficiency | \n
Randomized controlled trials for citalopram in chronic pain management.
Escitalopram (Cipralex™, Lexapro™) has antidepressive effects in 10–20 mg daily dose. For chronic low back pain, citalopram has similar results compared to duloxetine [53]. It has pain-relieving effects in painful diabetic neuropathy and somatoform disorders [54, 55]. For the treatment of pain symptoms associated with depression, escitalopram is equally effective with nortriptyline [56].
\nSNRIs are first-line antidepressants known to inhibit the reuptake of serotonin and norepinephrine almost exclusively by binding to their transporters (SERT and NET). This category includes drugs with very different chemical structure and includes venlafaxine, desvenlafaxine, duloxetine, milnacipran, and levomilnacipran.
\nSNRIs show different pharmacokinetics and dynamics and also different affinity to SERT and NET with consequences on their therapeutic actions (Table 4).
\nSide effects of SNRIs are common to all antidepressants, but these drugs add dry mouth and constipation due to increased levels of noradrenaline. The risk of withdrawal because of side effects, in patients with chronic pain, was highest for milnacipran and followed by venlafaxine and duloxetine [57].
\nVenlafaxine (Effexor™) is an SNRI with mixed action on amine reuptake. When administrated in low doses, it inhibits SERT and at higher doses NAT. It is indicated for major depressive disorder (MDD) and also for anxiety, panic disorders, and social phobia management.
\nAn experimental study showed its antihyperalgesic effect after a single administration in a diabetic neuropathic pain model, a result reversed by pretreatment with yohimbine and chloroamphetamine, but not by naloxone [58].
\nLong ago, a short case report raised attention to the potential beneficial effect of venlafaxine in chronic pain management [59], and later others confirmed its beneficial effects in managing neuropathic pain: peripheral neuropathy, postherpetic neuropathy, headache, and multiple sclerosis. In a systematic review on neuropathic pain, the authors found four trials (high quality evidence): two with positive results at doses of 150–225 mg venlafaxine ER daily and two with negative results (lower doses). The number needed to treat (NNT) was 6.4 and the number needed to harm (NNH) was 11.8 [60].
\nIn elderly patients with low back pain and depression, 150 mg venlafaxine showed efficacy, but the authors suggested that patients who did not respond to small doses may benefit from dose augmentation after a 2-week period [61].
\nVenlafaxine may be useful in the treatment of spinal cord injury (SCI) associated with MDD because this medication improved SCI-related disability and pain. Still, further trials are needed to determine optimal doses and efficiency in patients with SCI without MDD [62, 63].
\nStudies in patients with taxane-oxaliplatin-induced neurotoxicity showed clinical improvement after venlafaxine (37.5 mg bid) [64], and further studies are in progress [65].
\nVenlafaxine had good results in acute pain; in patients with cancer breast surgery, the preoperative administration of 37.5 mg venlafaxine reduced the postoperative opioid consumption and the incidence of chronic postoperative pain at 6 months [66].
\nA former Cochrane meta-analysis reported little evidence to support the recommendation of venlafaxine in neuropathic pain management and noted that venlafaxine promoted fatigue, nausea, dizziness, and somnolence with a low incidence [67].
\nEventually, two recent reviews (11 and 13 trials) found that venlafaxine was beneficial in neuropathic pain management with good tolerability claiming the necessity for further research to expand these findings [68, 69]. There are contradictory findings in these recent reviews, but there is need for further good quality evidence.
\nDesvenlafaxine (Pristiq™) is the third SNRI with FDA approval and only indication for MDD management (50–400 mg daily). The daily recommended dose is 50 mg. Desvenlafaxine is the salt of an active metabolite of venlafaxine, and the ER form allows 1 day administration. It presents a good bioavailability (Table 4) and shows a low binding to plasma proteins (30%). Desvenlafaxine binds to SERT 10 times more than to NAT and also has a weak affinity for dopamine transporter. Adverse effects are dose-dependent and typical to all antidepressants. Doses of 200–400 mg showed efficacy in DPN management, with effect sizes similar to duloxetine [70] and with increased side effects at higher doses. At the moment, there is a lack of evidence to support the use of desvenlafaxine in chronic pain management.
\nDuloxetine (Cymbalta™; DLX) is probably the most used drug from this class of antidepressants. Aside from MDD and urinary incontinence, duloxetine is indicated for anxiety disorder, chronic pain in diabetic neuropathy, fibromyalgia, musculoskeletal pain, and osteoarthritis. DLX is a potent SNRI, with a high affinity for both SERT and NAT. It has a moderate bioavailability, with an elimination half-time of 12 h. It is metabolized in the liver and does not possess any active metabolite. Duloxetine exerts antihyperalgesic and allodynic effects, by impairing nociception at a peripheral level (blocks NaV 1.7 current) and by inhibiting neuronal firing [71]. With acute administration, DLX leads to elevated levels of NA and 5-HT, and with chronic treatment, it does not affect further basal levels of these monoamines [72]. Even if the significant pain-relieving effect was found after 7 weeks of treatment [73], others showed that patients treated with DLX for OA knee pain or low lumbar pain who have <10% reduction in pain after 4 weeks treatment have low chance to reach moderate pain reduction by the end of 12 weeks [74]. DLX’s recommended dose for the first week is 30 mg, raising the dose to 60 mg in the second week in order to avoid a high incidence of side effects.
\nBecause of interfering with platelet function, it is indicated to stop its administration 4 days before surgery.
\nData from animal pain models and clinical studies on DLX administration in perioperative setting (spine, knee, breast surgery) suggested its analgesic effects. Pre- and postoperative duloxetine reduced 24-h opioid consumption, delayed first analgesic requirement, and reduced incidence of chronic postoperative pain at 6 months, being of primary interest for patients with preoperative chronic pain and spine surgery [75, 76, 77]; results from ongoing studies will respond to questions remained unanswered. Duloxetine shows good tolerability with dizziness and nausea, dry mouth, and constipation, as more frequent side effects [78].
\nWhile duloxetine proved its efficacy in chronic nociceptive/neuropathic pain [79, 80, 81, 82, 83] (Table 5), it is yet unrevealed its possible impact on acute postoperative pain and chronic postoperative pain.
\nSNRI | \nBioavailability (%) | \nElimination half life | \nElimination | \nSERT affinity | \nNAT affinity | \nActive metabolite | \n
---|---|---|---|---|---|---|
Venlafaxine | \n45 | \n5 h (IR) 11 h (ER) | \nRenal | \nHigh | \nLow | \nYes | \n
Duloxetine IR | \n50 | \n12 h | \nRenal + feces | \nHigh | \nHigh | \nNo | \n
Milnacipran | \n85 | \n8 h | \nRenal (55% unchanged) | \nModerate | \nModerate | \nNo | \n
Desvenlafaxine | \n80 | \n11 h (IR) 13–14 h (ER) | \nRenal (45% unchanged) at 72 h | \nHigh | \nLow | \nNo | \n
Levomilnacipran | \n92 | \n12 h | \nRenal 58% unchanged | \nLow | \nHigh | \nNo | \n
SNRIs pharmacokinetics and pharmacodynamics.
SERT, serotonin transporter; NAT, noradrenaline transporter; IR, immediate release; ER, extended release.
Study | \nPathology | \nNo trials | \nNumber of patients | \nFindings | \n
---|---|---|---|---|
Lunn et al. [79] 60 mg | \nDiabetes fibromyalgia | \n14 8-DPN; 6-FM | \n6407 | \nIn both category showed efficacy DPN-NNT 5 FM-NNT 8 | \n
Quilici et al. [80] | \nDiabetes | \n11 | \n679 | \nEffective in DPN NNT = 5 Good toleration Superior to placebo Discontinuation due to AE | \n
Wang et al. [81] 60/120 mg (QD) | \nKnee osteoarthritis | \n3 | \n1011 | \nSignificant pain reduction Improved function Reported “acceptable” AE | \n
Lee and Song [82] | \nFibromyalgia | \n9 | \n5140 | \nResults showed equal efficacy and tolerability | \n
Hauser et al. [83] | \nFibromyalgia | \n10 | \n6038 | \nSmall benefit over placebo | \n
Meta-analysis for duloxetine in chronic pain management.
QD, quaque die; DLX, duloxetine; MLC, milnacipran; DPN, diabetes polyneuropathy; NNT, number needed to treat; FM, fibromyalgia; AE, adverse effect.
Milnacipran (Savella™) described in 1998 by Briley as a potent SNRI that showed similar inhibition on both monoamine re-uptakes, in vitro and in vivo, was approved in Europe for the treatment of depression. It did not link to alpha adrenoreceptors, muscarinic cholinergic, and histaminic receptors and showed no effect on beta-adrenergic receptors sensitivity, thus having reduced side effects. The drug has an excellent bioavailability with a mean peak plasma concentration reached between 0.5 and 4 h after the oral administration. About 13% binds to plasma proteins and is wholly eliminated after 36 h [84]. Studies on the efficacy of milnacipran in psychiatric patients revealed its significant superiority when compared to SSRIs. Most frequent adverse effects were nausea, dry mouth, and headaches [85]. Milnacipran has FDA approval for the management of fibromyalgia.
\nIn 2006, Obata et al. found that intrathecal administration of milnacipran reduced allodynia in a rat neuropathic pain model [86].
\nOther experimental data confirmed these findings regarding milnacipran’s antiallodynic and antihyperalgesic effects [87] and showed its effectiveness in treating allodynia in vincristine-induced neuropathic pain [88].
\nIn a Cochrane meta-analysis, Cording et al. analyzed six studies (4238 patients) that compared milnacipran 100/200 mg with placebo in fibromyalgia. By using a “conservative” method of analysis, they found 26% positive response with milnacipran as compared to 19% for placebo and an increased rate of side effects [89].
\nDespite the evidence that milnacipran (100 or 200 mg) was found to be useful in neuropathic pain, as compared with placebo, Derry et al.’s meta-analysis did not obtain enough data to confirm former data and support its recommendation in chronic neuropathic pain [90]. Future trials are needed to establish milnacipran’s possible favorable effects in pain management.
\nLevomilnacipran (Fetzima™) is the enantiomer of milnacipran with the highest activity, and its primary indication is MDD. At usual doses, this drug is known to possess a higher potency for norepinephrine (twofold) reuptake inhibition, as compared with 5-HT [91]; but with higher doses, it showed equal efficacy in increasing 5-HT and NE levels [92].
\nRegarding tolerability, the most frequently recorded adverse effects were nausea, constipation, and sweating, although a small proportion (3–6%) of patients recorded increased blood pressure and heart rate [93]. We have not found any data regarding its use in chronic pain patients.
\nA particular category of drugs includes SRIs with double mechanism: 5-HT reuptake inhibition and interaction with 5-HT receptors. Animal studies have suggested that these receptors are included in the descending pain inhibitory systems [94, 95], and their activation is involved in reducing the acute nociceptive and neuropathic pain [96].
\nTrazodone (Desyrel™, Oleptro™) is the first non-tricyclic antidepressant approved for the treatment of MDD (1981), and it is also used to treat anxiety, alcohol dependence, insomnia, and chronic pain (off-label). It was developed for the treatment of “mental pain,” which was recognized to occur in depression [97]. It acts as a SRI, antagonist of 5-HTA2 receptor, and a partial agonist for 5-HTA1 receptors. Secondary acts as an antagonist to α1-adrenergic receptors and lacks any effect on cholinergic receptors. The drug shows a 65% oral bioavailability, 90% plasma protein binding capacity, and is metabolized in the liver (via CYP3A4) to an active metabolite—mCPP. The main excretion route is renal, and the biological half-time is 7 h. Side effects are not only shared with the other antidepressants but also list dry mouth, orthostatic hypotension, cardiac arrhythmias, and priapism.
\nTrazodone showed some efficacy in several chronic pain conditions represented in Table 6, but future studies are needed.
\nStudy | \nChronic pain condition | \nDose | \nNumber of patients | \nComparator | \nEfficiency | \n
---|---|---|---|---|---|
Wilson [103] | \nDiabetic neuropathy | \n50–100 mg | \n31 | \n— | \nEffective | \n
Ventafridda et al. [104] | \nDeafferentation pain | \n— | \n45 | \nAmitriptyline | \nEqual efficacy | \n
Goodkin et al. [105] | \nChronic low back pain | \n201 mg (average) | \n42 | \nPlacebo | \nSimilar effect | \n
Morillas-Arques et al. [106] | \nFibromyalgia | \n50–300 mg | \n66 | \n— | \nEffective | \n
Calandre et al. [107] | \nFibromyalgia | \n50–300 mg trazodone + 75–450 mg pregabalin | \n41 | \n— | \nPregabalin enhanced the favorable effects of trazodone | \n
Davidoff et al. [108] | \nDysesthetic pain following spinal cord injury | \n150 mg | \n18 | \nplacebo | \nSimilar effect | \n
Battistella et al. [109] | \nMigraine (pediatric 7–18 years) | \n1 mg/kg | \n40 | \nplacebo | \nEffective | \n
Frank et al. [110] | \nRheumatoid arthritis | \n1.5 mg/kg | \n47 | \n— | \nNo effect | \n
Trials for trazodone in chronic pain management.
Nefazodone (Serzone™) is related to trazodone but with fewer side effects. Doses of 300–600 mg are indicated for the treatment of MDD, panic disorders, and aggressive behavior. It acts as an antagonist of 5-HTA2 and 5-HTC2 receptors and serotonin, norepinephrine, and dopamine reuptake inhibitor. Its effects on the mentioned receptors enhance neurotransmission by an increased binding on the 5-HTA1 receptors. Nefazodone shows an affinity for α1 and less for β-adrenoreceptors and does not interact with muscarinic cholinergic receptors. It has low bioavailability; it is metabolized in the liver (CYP3A4) and has four metabolites (mCPP active). Nefazodone has a biological half-time between 2 and 4 h and is excreted in urine. Frequent side effects are dry mouth, dizziness, and sleepiness, and rare, severe liver damage [98].
\nMurine studies yielded the capacity of nefazodone to potentiate opioid analgesia by acting through μ1 and μ2 receptors without affecting mortality [99]. Other results indicated that rats treated with nefazodone have shown an increased expression of μ-opioid receptors in the area of the central nervous system related to pain perception and modulation [100].
\nEven if it shows an excellent clinical profile, at this time we found only a two-center open-label study on the efficacy of nefazodone on preventing chronic daily headache. The study included 52 patients who received nefazodone between 100 and 450 mg (300 mg median) for 12 weeks. The results showed significantly lower incidence and intensity of daily headache and a good tolerance for nefazodone [101].
\nVilazodone (Viibryd™) approved by FDA (2011) for the treatment of MDD is a partial agonist to the 5-HTA1 receptor, GABA agonist, and SRI. Currently is presumed that it increases serotoninergic neurotransmission and it shows fast onset and good effect at daily doses between 10 and 40 mg. Vilazodone has 72% bioavailability when it is taken with food, is metabolized in the liver (via CYP3A4), and it did not possess active metabolites. It is excreted in urine and feces and has a biological half-time of 25 h [102]. Side effects include nausea, vomiting, diarrhea, and insomnia (>5%). Sexual adverse reactions and low influence on weight-gain were reported [103]. Even if it presumed that vilazodone should add value in the treatment of patients with the depression-pain syndrome, there are not yet available data on its efficacy in pain states.
\nSSRIs seem to be effective in most chronic pain conditions, and they are well tolerated [41]. The efficacy of SSRIs might be comparable to TADs and SNRIs, but their tolerability and safety are superior [30]. For some chronic pain conditions, valuable, while for others their utility is limited:
For migraine, SSRIs are not better than placebo for reducing the number of attacks, and results of studies on migraine are conflicting [24, 111].
Patients with chronic tension-type headache seem to benefit from SSRIs [24].
There are conflicting results regarding the use of SSRIs for pelvic pain.
Non-cardiac chest pain might benefit from SSRIs.
Low back pain does not seem to respond well to SSRIs.
The effects of SSRIs on fibromyalgia are uncertain [112].
Diabetic neuropathy looks to improve from SSRIs treatment.
Post stroke central pain might improve with fluvoxamine.
Evidences support that antidepressants are useful for the treatment of irritable bowel syndrome [113].
There is no evidence from randomized controlled trials to recommend antidepressants to treat chronic non-cancer pain in children and adolescents [114] or adults.
Even though several clinical trials were published, the results remain inconclusive. That happens because the sample sizes are quite modest rendering the studies slightly underpowered. Primary outcomes are variable: self-reported pain scores, effect on pain symptoms observed by the physician, complex pain questionnaires, and effects on quality of life and functionality. Current drug classes available for chronic pain treatment include anti-inflammatory drugs, opioids, gabapentinoids along with interventional or surgical management, and physical activity. Heterogeneity of the chronic pain syndromes, many currently available drugs and treatment modalities, and drug-drug and drug-interventional management associations should be considered when designing future larger scale trials.
\nIn conclusion, compared to all other antidepressants in the management of chronic pain, for SSRIs, the data are still inconclusive, and studies are fewer in number. For depression, SSRIs are considered first-line agents due to a favorable side-effect profile and good tolerability. However, they have not yet entered first-line use for neuropathic pain conditions [12]. Probably, it would be advisable to restrict their use for those patients failing to respond to other medications or who do not tolerate side effects.
\nFrom SNRIs category, in particular duloxetine is already a first-line treatment for DPN and other chronic pain syndromes (fibromyalgia, musculoskeletal pain, and osteoarthritis), showing good results and an acceptable safety profile. It also showed favorable effects on chronic postoperative pain and life quality with the perioperative administration in surgery with a high incidence of chronic pain (spine, breast). Venlafaxine is a drug of choice for the treatment of fibromyalgia. Milnacipran proved antiallodynic and antihyperalgesic effects and might show further positive results in chronic pain management; well-designed trials are still required.
\nSRIs seem to play their role through the spinal modulation pain pathways being less involved in reducing nociception, and that is probably why their effects are more evident in patients with chronic pain states.
\nNothing to declare.
The development of the coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, triggered a global scenario of socio-economic catastrophe and psychological anguish. Many psychological problems and essential mental health consequences, including stress, anxiety, depression, frustration, uncertainty during the COVID-19 outbreak, emerged progressively.
In response to this dire circumstance, specific public policies were introduced by governments globally. These measures include self-quarantine, isolation, and social distancing. Implementing these policies caused the closure of educational institutes, offices, workplaces, public places, and social gathering restrictions. People were advised to stay at home and follow advice proposed by the WHO to protect themselves and others from the spread of COVID- 19. The strict self-quarantine order (lockdown) has kept the entire population in selected jurisdictions in isolation, with a significant impact on people’s life [1]. Although social activities have been restricted in most countries, almost all non-essential individual movements were prohibited due to quarantine, while the local hospitals received suddenly thousands of critically ill COVID-19 patients and were forced to implement their emergency protocols.
In this context, the general population and most of the front-line healthcare workers became vulnerable to the emotional impact of COVID-19 infection due to both the pandemic and its consequences worldwide. The modern society, in which everyone can travel and communicate quickly, has seldom been subjected to the present social isolation and constraints associated with feelings of dissatisfaction and uncertainty. This unusual scenario surrounding the COVID-19 epidemic illustrates that people are fundamentally and emotionally unprepared for the negative impacts of biological disasters, which immediately highlight how everyone may be vulnerable and helpless.
There is a constant update about the disease available on news channels and over the Internet, highlighting the number of individuals affected and deaths due to COVID-19. Also, inadequate knowledge and overwhelming news may contribute to fear and anxiety among the public. People at large may experience disappointment, irritability, and boredom under isolation measures [2]. The communication technologies’ facilities and transmission of inaccurate or sensational information may increase unacceptable social reactions such as aggression and rage [3].
The psychological reactions to the COVID-19 pandemic may vary from panic behavior or collective hysteria to pervasive feelings of hopelessness and desperation associated with adverse outcomes, including suicidal behavior [4]. Significantly, other health measures may be compromised by abnormally elevated anxiety. According to the social role invested, the security measures adopted in managing the pandemic had different consequences on individuals. Suspected and confirmed COVID-19 cases are likely to experience anxiety, loneliness, depression, denial, insomnia, and fear [5]. Health authorities’ strict quarantine policy and mandatory contact tracing policy may lead to social rejection, discrimination, financial loss, and stigmatization. Medical health workers are first-line fighters treating patients with COVID-19. They are a unique subset of exposed individuals as they are equipped with the resources and knowledge to address the dangers imposed by a pandemic. Despite this, they are not impervious to the detrimental impact of the pandemic on their psychological health and behavior. During the challenging times of a pandemic, healthcare workers, the most exposed group, are vulnerable to psychological challenges. Every day, they face a high risk of being infected and are exposed to prolonged and distressing work shifts to meet health requirements. This has placed healthcare workers around the world in an unprecedented situation.
This epidemic, as well as the public health measures put in place to slow it down, has drastically altered people’s lifestyles and is believed to pose a threat to their physical and mental health. This significant health catastrophe is impacting numerous countries, with high rates of transmission and death, and extensive outbreaks and mortality are linked to negative mental health consequences.
Strasner (1987) defined fear as “an emotional reaction (rational or irrational) to an object (animate or inanimate) or event that is associated with increased risk of danger and also unpleasantness, agitation and a desire to hide, flee or seek protection.” Phobia, on the other hand, is characterized by intense, severe, and persistent fear. Such fears lead to persistent efforts to avoid (flee) the source of distress, often by undertaking a number of “safety behaviors”. As a new infection with the potential for loss of life, COVID-19 has provoked legitimate fears. However, in a minority of subjects, this has also led to extreme restrictions, which could be characterized as “coronaphobia” [6]. Adequate communication that engenders a realistic appraisal of the risks, along with clear statements of behaviors that can reduce transmission, have been effective to control these fears, while also preventing viral transmission.
SARS-CoV2 infected patients experienced a high degree of fear stemming from uncertainity of illness outcome, inability to communicate with family members, lack of complete knowledge of the disease process and the stigma associated with being infected with the virus. Morever, the fear of isolation, discrimination and stigmatization was also noted in this group [7]. Those patients suspected to have SARS-CoV2 infection are also prey to the terror of having the disease, advancement of disease, precariousness of healthcare delivery and quarantine as per government regulations. Besides, even patients suffering from other illnesses displayed features of trepidation of inability to receive proper treatment due to overwhelmed healthcare resources. Patients with chronic diseases like diabetes, TB, and heart failure, for example, were found to avoid seeking medical treatment because they were afraid of contracting the illness from others in a healthcare facility, adding to fear of contagion. The type of chronic disease is a significant predictor of fear with higher levels noted among those diagnosed with autoimmune diseases or receiving immunosuppressants [8].
Despite being the highest risk exposure group, healthcare workers have been found to experience less fear compared to the patient population as well as the general public. In a study conducted in India it was observed that a mere 18.3% healthcare workers reported of fear of contracting the infection. Most healthcare workers displayed concern and fear of transmitting the infection to their families and loved ones, especially to their children and the elderly [9]. Higher levels of fear were present in lab technicians, X-ray technicians and nurses while physicians were found to have the lowest level of fear. A possible explanation of this is that technicians and nurse have more exposure to contracting the illness during sampling, testing and medication of patients [10]. Non-medical healthcare workers were assessed to have lowest fear quotient juxtaposed to medical healthcare workers who are usually in direct contact with SARS-CoV2 infected patients and have a better understanding of the disease and its mortality [11]. Alike patients, healthcare workers are not immune to the fear of social marginalization. Assault on doctors, eviction of resident physicians from their rented houses, and fear of infection from healthcare workers have all been reported [12, 13]. These factors alongwith the shortage of sufficient protective equipment, absence of effective therapy and the virus’s high infectivity rate might possibly play a role in their fearfulness of coronavirus pandemic. The presence of fear among HCWs poses a significant threat to their psychological adjustment skills and impede delivery of optimum care to patients.
Claude Bernard noted that the maintenance of life is critically dependent on keeping our internal milieu constant in the face of a changing environment. In 1956, Selye coined the term “stress” to represent the effects of anything that seriously threatens homeostasis. The actual or perceived threat to an organism is referred to as the “stressor” and the response to the stressor is called the “stress response.” Although stress responses evolved as adaptive processes, Selye observed that severe, prolonged stress responses might lead to tissue damage and disease. During pandemics, the victims and at-risk groups tend to experience stress. As a consequence of the pandemic, even the health professionals who were overworked suffered high level of psychophysical stress. Various tools and questionnaires have been devised to measure stress levels in individuals. The most commonly used are DASS-21 and SAS. Studies have shown that psychological stress can affect the immune system through neuroendocrine pathways [14].
The increasing number of confirmed cases, a lack of knowledge of COVID-19, the rapid transmission rate, infection fears, lockdown conditions, difficulties in routine medical treatments, shortages of human resources in hospitals, insufficient psychological preparation, separation from loved ones, financial loss, stigma, loss of freedom, and uncertainty over illness status act as significant stressors for patients. These patients often display features of distress such as feeling nervous, worried in certain situations of panic, tendency to overreact, inability to control things in life, inability to overcome difficulties in daily life, and coping with things. The early months of pandemic had the higher reported prevalence of stress with a significant proportion of individuals reporting being upset due to things happening unexpectedly, inability to overcome difficulties in daily life, and anger at things being outside their control. Among suspected patients, those with history of travel to areas with ongoing community transmission were found to display greater stress [15]. Patients who are kept in isolation and quarantine experience significant levels stress as well [2]. It is expected that individuals may resort to social media during corona-led social distancing for stress relief and with the aim of accessing entertaining content, such as movies, comedies, and communication with family and friends, but frequent media exposure may itself be a source of psychological stress for these patients [16, 17]. Distress and panic during pandemics can propagate and promote misinformation in various ways along with increased digital screen time and unhealthy use of technology. Amid this, there has been a hidden epidemic of “information” that makes COVID-19 stand out as a “digital infodemic” from the earlier outbreaks. Misinformation and fake news are invariable accompaniments to this “information pollution” which can add to existent superior stress levels in the population [18]. Unfortunately, even immunocompromised and chronic disease patients are under tremendous psychological and physical stress in the face of this large-scale infectious public health crisis due to lack of proper healthcare infrastructure and treatment [19, 20, 21].
Amid the ongoing unforeseen situation of coronavirus disease 2019 (COVID-19) pandemic, health care workers of multiple disciplines have been predisposed to a considerable amount of stress. A statistically significant association was found between perceived stress and female sex, designation (postgraduate trainees), work hours ≥6 hours/day, COVID-19 positive ward duties and staying with family due to potential risk of transmission to family members [22]. Disturbed sleep time and schedules due to rotational duties exhaust these HCWs both physically and mentally. The physical discomfort and occupational dermatoses associated with the use of PPE have also been shown to be related to greater levels of stress symptoms [23]. Practicing new methods of a discipline different than what he/she has mastered over the years, long hours of working in extreme conditions under PPE kit discomfort, long duty hours with no food/water/urination allowed during the time of duty with PPE, and irritation and physical strain in PPE during the summer season have been constant precipitators of stress among the doctors of all the disciplines working as frontline warriors [22]. With a scarcity of resources and an ever increasing number of patients, life-saving decisions have to be made. Making such decisions amid intense work pressure leads to added stress within emergency departments as well as during after-duty hours [24]. All doctors are susceptible to developing higher stress irrespective of their discipline during the COVID-19 pandemic, and this is further precipitated by their quarantined living conditions [22, 25]. Older HCWs demonstrate a high level of psychological distress, possibly as a result of increased complications of COVID-19 with increasing age and also because older people may have health issues making them more prone to infection with its complications [26]. In conclusion, HCWs are exposed to a protracted source of distress which may exceed their individual coping skills and lead to further chronic psychological problems.
Anxiety is an emotion characterized by the feeling of tension, worried thoughts and physical changes such as increased heart rate, according to the American psychological association. Since the onset of pandemic, many studies have been conducted to ascertain the prevalence of COVID-19 related anxiety among various sectors of the population. Conventional tools utilized to assess anxiety are:
Depression, anxiety and stress scale-21 (DASS-21)
Self-rating anxiety scale (SAS)
Generalized anxiety disorder scale (GAD-7)
Chinese version of GAD-7 scale
Hospital anxiety and depression scale (HADS)
The magnitude of anxiety varies across the country of origin of study, measurement tool used and size of the studied sample.
Patients suspected or diagnosed with SARS-CoV2 infection experience significant anxiety related to disease and external factors associated with having the infection. Several patient related factors influence the vulnerability to anxiety such as sex, marital status, symptoms and sleep quality, among others [27, 28, 29, 30]. There are many patient-related factors associated with anxiety such as:
Female gender
Older age
Divorce/bereavement
Married
Residing with family
Need of oxygen inhalation
History of fever
Two or more symptoms of infection
Suspected/confirmed infection
Poor sleep quality
Quarantine/isolation
The external factors include spread of misinformation by media, government regulations such as quarantine procedure, lockdown and travel restrictions, and social stigmatization. The current pandemic underlined the vital role played by media in dissemination of information. Ideally, media should ensure that crisis communication helps in dispelling fear and uncertainty, but in the recent pandemic it played a reverse role in spreading anxiety and panic behavior [31, 32, 33]. The endless newsfeeds related to COVID-19 infection and death rates considerably increased the adverse psychological outcomes in general population as well as patients. The spread of misleading narratives, provoking controversies and advertisement of unapproved therapies resulted in widespread fear, confusion and panic with serious mental health consequences such as anxiety [34, 35]. Quarantine and isolation of suspected and confirmed cases as per government regulations also led to abnormally increased anxiety. Additional measures like lockdown and travel restrictions also contribute to feeling of uncertainty, perceived lower social support, separation from loved ones, loss of freedom and boredom [2]. Notably, individuals with a previous health disorder experienced worsening of their symptoms due to anxiety.
Healthcare workers are directly involved in diagnosis, treatment and care of SARS-CoV2 patients and therefore experience the highest share of mental health issues compared to the other groups in the population. The prevalence of anxiety among healthcare workers is high and has been assessed to be between 23.2% to 30.5% [36, 37]. Several factors have been attributed to cause anxiety in healthcare workers. These include increased workload, inadequate PPE, inadequate isolation precautions, risk of contracting disease, high infectivity and mortality of disease, burnout, lack of clinical experience, young age, chronic health illness and prior history of mental health disorders [31, 32, 33]. Socio-demographic variables play a key role in determining the level of anxiety in healthcare workers with higher prevalence among those above the age 40, females, unmarried individuals and presence of offspring [38]. Anxiety in this group manifests as palpitations, tremors, dryness of mouth, feeling scared without any reason and tendency to panic [15]. These symptoms are more prevalent in workers who were assigned duties in COVID designated areas and those who encountered SARS-CoV2 suspected or confirmed patients without adequate protection [5]. Nurses have unfavorable mental health outcomes among the healthcare staff since they usually spend more time caring for patients than any other group of HCWs [11, 36, 39]. The existence of anxiety is associated with reduced performance and fatigue in healthcare workers and impedes optimum healthcare delivery to the population.
Depression is one of the five most incapacitating illnesses, and by 2030, it is expected to be one of the major issues in industrialized countries. It’s a common reaction to a rapid deterioration in living conditions, which involves isolation and uncertainty. When people are subjected to unpredictable circumstances, they feel helpless and unmotivated, which can lead to sadness [40]. During past epidemic outbreaks (SARS and Ebola), rates of depression in the general population have been reported with a prevalence approaching even 73.10 percent [41]. Past epidemics were more quickly contained, and infection rates were lower despite greater fatality rates, which might explain why depressive symptoms were less common [42]. Furthermore, during the SARS pandemic in Canada, Hawryluck et al. discovered that the length and unpredictability of the lockdown contributed to greater levels of depression [43]. As a result, the present global lockdown measures might explain the increased incidence of depressive symptoms reported during the COVID-19 epidemic. According to a research that looked at 69 million health data from over 62,000 persons diagnosed with COVID-19, 6% of COVID-19 patients suffered mental health problems including sadness and anxiety within three months of diagnosis, compared to 3.4 percent of non-COVID-19 patients [44]. The addition of a psychological burden to an already devastating physical burden affects the prognosis in a number of ways, with long-term consequences. Furthermore, those who are depressed are less likely to seek treatment for physical or mental problems; as a result, depression, like anxiety, can act as a barrier to reasonable medical and mental health interventions during a pandemic.
Earlier outbreaks such as SARS and MERS have displayed the presence of depressed mood among those with acute infection [45]. The COVID-19 pandemic is no different. The reported prevalence of depression at 6% in COVID-19 patients is higher to general population [44]. Females are more likely to experience depression than males [46]. According to one study, nearly one-fourth patients had intended to commit suicide or harm oneself [27]. Individuals who were married or underwent a divorce exhibited greater levels of depression than single individuals [27]. This could in part be explained by worries for one’s family and grief of separation respectively. Having a family member with confirmed COVID-19, and having two current physical symptoms are independent risk factors for depressive symptoms [28]. Suicide has become a more pressing concern as the pandemic evolved [47]. Those with psychiatric disorders experience worsening symptoms and others are predisposed to develop depression, are all associated with increased suicide risk. Media and other news platforms also affect mental health and psychological behavior [35]. Despite the fact that receiving regular updates on COVID-related health information appears to reduce sadness, it is also claimed that social media exposure is linked to depression and mixed anxiety and depression [48, 49, 50]. Unemployment, low social status, a lack of social support, and financial losses are among socioeconomic variables that might contribute to greater incidence of depression. [48, 49, 51, 52]. The added impact of quarantine has led to high occurrence of depression and even self-reported suicidal thoughts [29, 53].
The COVID-19 pandemic has significant negative impacts on healthcare workers’ psychological health, fostering anxiety, depression, and sleep disturbance. Studies conducted during the SARS have reported a prevalence of depression among the front-line HCWs to be 38.5% [54]. The factors in play causing depression are pretty similar to those contributing to anxiety. Increased workload, burnout, inadequate PPE, the risk of contracting the disease, and the challenge of making difficult moral decisions about care priorities during the pandemic have exposed healthcare workers to severe psychological pressures leading to depression. The high infectivity and mortality rates also contribute to depression among healthcare workers around the world. Furthermore, factors such as a high-risk workplace, a lack of clinical experience, young age, and a history of psychological disorders can contribute to depression among healthcare workers. Working on the front lines was found to be an independent risk factor for poor mental health outcomes across all aspects studied, including the prevalence of depression among HCWs. Between doctors and nurses, the latter have been studied to harbor a greater level of depression [55, 56, 57]. This may be partially confounded by the fact that nurses are primarily female but could also be attributed to the fact they may face a greater risk of exposure to COVID-19 patients as they spend more time onwards, provide direct care to patients and are responsible for the collection of sputum for virus detection [55].Emotional exhaustion, depersonalization, being a nurse, 12- or 24-hour shifts or on-call hours, those who live with people who are at risk, and being very concerned about a possible infection of a family member they do not live with are all positively and significantly related to having depression symptoms [58]. Depression is also significantly higher among HCWs who did not know the latest COVID-19-related research/information. Lack of information may precipitate mental health concerns, and prior studies have suggested that updates and knowledge about COVID-19 may have psychosocial impacts, possibly as they represent an active way of coping and dealing with pandemic-related issues [59, 60]. Research also indicates that healthcare workers who take vacation days experience lower levels of depression [26]. Unfortunately, the COVID-19 pandemic crisis witnessed doctors along with other healthcare workers question their choice of profession, in part due to rising infection rates, unavailability of adequate personal protective equipment and other unexpected pandemic related experiences [60].
Long COVID is a term used to describe a condition in COVID-19 patients who have symptoms over an extended period [61]. These patients report prolonged, multisystem involvement and significant disability, which can last for more than six months in 93.2% of patients after the acute phase of illness [62]. Musculoskeletal, cardiovascular, gastrointestinal, pulmonary, and neuropsychiatric symptoms are prevalent in >85% of participants. Fatigue, breathing problems and cognitive dysfunction are among the most debilitating symptoms [62]. Such prolonged physical sequelae are associated with and often are a harbinger of psychological sequelae. Multiple studies conducted during previous pandemics also support the development of psychiatric sequelae in survivors. SARS-CoV-1 survivors exhibited posttraumatic stress disorder (PTSD) with an incidence of up to 55%, depression was observed in 39%, pain disorder in 36.4%, panic disorder in 32.5%, and obsessive–compulsive disorder in 15.6% of SARS-CoV-1 survivors [63]. Long term psychiatric complications such as depressed mood, anxiety and insomnia were also reported in 10-20% of patients following SARS and MERS infections [45]. These complications could result from central nervous system involvement of the virus or perhaps a consequence of fear associated with the infection and isolation itself.
Among the psychological sequelae, the most prominent and popular condition is posttraumatic stress disorder [64]. Surviving a critical illness is known to induce PTS symptoms [65]. Data suggests that as many as 43% of COVID-19 patients suffered posttraumatic stress symptoms [66], ‘not though true prevalence of PTSD’ prevalence. The severity of COVID-19 poses a significant risk factor for PTSD, supported by evidence of higher incidence among ICU patients juxtaposed to non-ICU patients [67, 68]. Even measures of quarantine and isolation, which help to contain the infection from the spread, can have psychological consequences leading to PTSD [2]. Healthcare workers, too, experience significant PTS symptoms. Emotional fatigue, depersonalization, working in a hospital, being highly concerned that someone they live with may become infected, and believing that becoming infected with COVID-19 is very likely are all positively and substantially associated with posttraumatic stress symptoms in the HCW population [56].
Aside from PTSD, COVID-19 infection survivors are more likely to experience depression and anxiety, similar to the acute phase of the disease [64]. The incidence of these disorders is linked to the severity of the disease and the length of hospitalization [69, 70, 71]. The baseline systemic inflammation index (SII) is strongly correlated with anxiety and depression [45, 59]. At follow-up, the prevalence of baseline comorbidities, such as mental disorders and female sex, is also linked to depression and anxiety [71, 72]. Although anxiety and depression symptoms generally go away within 1-3 months after infection, their presence increases the risk of developing PTSD later on [61].
Worldwide epidemiological research is urgently needed to evaluate the amount of anxiety, worry, and helplessness and other mental health concerns related to COVID-19. This would aid in developing tailored mental health initiatives (e.g., those who live in villages). Experiences from past pandemics point out the urgent need for screening for mental health problems, monitoring its trend, referral of cases, and providing suitable interventions has to be routine practice during the pandemic period [73, 74]. The target groups of such screening strategies must include COVID-19 infected patients, their high risk contacts, and healthcare workers, as well as those with past history of mental health illnesses. The following questionnaires may be utilized for routine screening:
COVID-19 stress scale [75]
Perceived Stress Scale modified for COVID-19 (PSS-10-C) [76]
COVID-19 Peritraumatic Distress Index (CPDI) [1]
Anxiety of COVID Scale (CAS) [77]
Fear of COVID-19 Scale (FC-19S) [78]
COVID-19 Pandemic Mental Health Questionnaire [79]
The abovementioned questionnaires were newly developed or modified versions of existing mental health screening questionnaires. It is therefore emphasized that the pre-existing validated survey tools such as GAD-65, PSS-10, PHQ-9 and DASS-21 can be also utilized for routine screening purposes and have been validated for the same.
During the pandemic, marginalized groups such as those with chronic health conditions, mental health issues, and the elderly must continue to get health care. Provisions such as telemedicine and clinics independent from COVID-designated facilities should be guaranteed for optimal healthcare delivery in a continuum.
The mental health and emergency management communities should collaborate to seek, develop, and disseminate evidence-based resources on disaster mental health, mental health triage and referral, unique populations’ requirements, and death communication and bereavement support.
Health care professionals should help patients manage stress and cope (by organizing activities and sticking to routines), introduce patients to social and mental health resources, and encourage them to seek professional mental health help if necessary.
While most psychological health services can be provided in primary care settings, a few patients will require comprehensive mental health assessment and care, while others might benefit from supportive interventions targeted at enhancing wellbeing and coping such as psychoeducation or cognitive behavioral therapy.
Patients with suicidal ideation shall necessitate immediate referral, hospitalization, and therapeutic intervention by a psychiatrist.
Tele-psychiatry services are vital to maintain the continuum of care in the COVID pandemic era. Certain modifications are warranted to enhance the delivery of tele-health services –
At each institution, teams of expert psychologists should be accessible for healthcare professionals to call at any time, and quick treatment and follow-ups should be given.
Peer support and group talks should be promoted as well. HCWs must be provided with stress management training.
During pandemic conditions, vacations from work are required to reduce psychological distress among healthcare professionals, resulting in decreased levels of despair, fear, worry, and stress. Therefore, healthcare professionals are urged to take vacations from work to help them relax, which helps reduce stress.
In regions where infrastructure is lacking, the government and health authorities must work together to provide PPEs and the essential infrastructure for HCWs to safely administer healthcare to their patients.
Health-care systems are required to address the stress on individual providers and overall operations by monitoring reactions and performance indicators, modifying assignments and timetables, moderating expectations, and developing effective mechanisms to deliver psychological support as required.
HCWs should be encouraged to self-monitor their own stress reactions and seek appropriate assistance. Systems must be in place to quickly identify HCWs who require psychological assistance, send them to a professional, and provide access to specialized consultations as well as intervention, if necessary. Setting up of grievance redressal system will be of great use for all the HCWs to raise any issue pertaining to their current work and prompt resolution and solutions can be offered.
The process of testing, quarantine and re-joining work should be streamlined and communicated to everyone working in the establishment.
A rotational basis in the work from highly stressful to low stressful duties can be considered.
Encouragement and establishment of a buddy system with buddies being aware of need for confidentiality and available resources to help the person in distress.
All HCWs should be encouraged to follow a healthy lifestyle such as having a daily routine, pursuing their hobbies and stress management and relaxation techniques such as yoga and breathing exercises.
Isolation and quarantine restrict one’s activities severely, causing worry and concern over not fulfilling one’s professional and familial obligations. While the methods and processes for mental health support and monitoring in quarantine accommodation differ by jurisdiction, there are several critical areas that should be included in national mental health screening, evaluation, and support protocols. These include:
It is necessary to set up telephonic/digital contact between the patients and their family members.
Psychological counseling should be offered in quarantine centers.
Provision of a clear rationale for quarantine and information about protocols
Prior to departure, throughout travel, upon arrival, and during the quarantine period, accurate and timely information is critical.
The provision of a structured day with meaningful activities and opportunities for social connection is critical to preserving mental health. From the start, active participation is required, as well as the availability of a variety of individual and group activities from which to pick. COVID-19-compliant group activities must be delivered, if necessary using virtual methods.
Every person in quarantine should ideally have access to fresh air through windows or a balcony, space to exercise, and healthy and culturally appropriate food options.
People should be actively and assertively engaged in activities, well-being checks, and information.
Effective governance necessitates that all providers involved in assisting persons under quarantine have clear lines of communication, information exchange, and complaint handling.
COVID-19 news, as previously discussed, has a positive linkage with depression, anxiety, and stress levels. It can be caused by erroneous statistics data and rumors that circulate through the internet. To avoid misleading information and public health statistics, the government and health authorities must offer accurate and up-to-date information. In this context, the research found that having access to current and accurate health information is linked to less stress. Up-to-date and exact data on the number of new and improved cases, available treatment methods, and transmission routes must be used to reduce the illness’s psychological and mental health effects. The psychological impact of misinformation/rumor on the mental health of HCWs and the general public might be greatly reduced if a public health information system that is accurate and updated is widely disseminated.
COVID-19 is linked to a range of psychiatric problems in addition to physical health issues. The spread of the novel coronavirus may have an influence on people’s mental health in many communities. Patients with COVID-19 have a significant rate of negative psychological occurrences. Frontline healthcare professionals caring for COVID19 patients have a high rate of stress, anxiety, and depression. As a result, health policymakers should take steps to regulate and prevent mental illnesses among hospital employees. During the COVID-19 epidemic, the mental health of HCWs is a major issue. Psychological interventions that detect and target persons with varying degrees of psychological distress are desperately required.
The authors declare no conflict of interest.
None.
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